17

Diabetes Mellitus Diabetes mellitus, by far the most common of all endocrine disorders, is one of the foremost public health concerns con- fronting the world today. Over 25.6 million individuals in the United States, or 8% of the population, have been diagnosed with diabetes. This number tripled between 1980 and 2011. Another 5.5 million are undiagnosed and unaware they have the disease.5 Prevalence has increased worldwide, from an estimated 30 million cases in 1985 to 382 million in 2013. The International Diabetes Federation projects that 592 million individuals will have diabetes by the year 2030.6 The average medical costs for a patient with diabetes in the United States are more than twice that of others receiving care, and are mostly associated with the accompanying chronic complications. Direct medical costs for care of individuals with diabetes totaled $116 billion in 2007. In 2010, 1.9 million new cases of diabetes were diagnosed in people age 20 years and older. It is the seventh leading cause of death in the United States and is likely to be underreported. Risk for death among people with diabetes is about twice that of those without diabetes.5 Diabetes mellitus is not a single disease but a diverse group of disorders that differ in origin and severity (see Box 17.1). Yet all forms of diabetes mellitus share one common characteristic: hyperglycemia resulting from defects in insulin production, insulin action, or both. Chronic hyperglycemia is correlated with organ dysfunction and damage, progressing to failure of numerous organs, particularly the eyes, kidneys, nerves, heart, and blood vessels.3 Insulin deficiency is generally due to either insufficient insulin secretion by beta (b) cells or comparative deficient response by target tissue cells to insulin.3 Whatever the cause of insulin deficiency, it results in glucose intolerance. The diagnostic criteria for diabetes mellitus are outlined by the "Standards of Medical Care in Diabetes—2014" from the American Diabetes Association (see Box 17.2).7

Classifications of Diabetes Mellitus I. Type 1 diabetes mellitus (b cell destruction with absolute insulin deficiency) II. Type 2 diabetes mellitus (progressive defective insulin secretion with insulin resistance) III. Gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy that is clearly not overt diabetes) IV. Diabetes due to other causes • Drug or chemical induced (such as after organ transplantation) • Genetic defects • Cystic fibrosis or other diseases of the pancreas V. Category of increased risk: Prediabetes (previously noted as impaired fasting glucose or impaired glucose tolerance) A $6.5% using standardized laboratory measures1 1c OR Fasting plasma glucose2 $126 mg/dL (7.0 mmol/L) OR Symptoms of diabetes3 plus random plasma glucose concentration $200 mg/dL (11.1 mmol/L) OR 2-hour post-prandial glucose $200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT)4

Type 2 Diabetes Mellitus in Children Colette LaSalle, PhD, RD San Jose State University Over the last two decades the prevalence of pediatric type 2 diabetes mellitus (T2DM) has increased dramatically. In fact, T2DM was once so uncommon in children that it was called "adult-onset diabetes" to distinguish it from type 1 DM, which was known as "juvenile-onset diabetes." The name was changed to reflect the fact that more and more younger people were being diagnosed with this disease; children, who used to represent ,3% of T2DM cases, now account for up to 45% of cases.1 This increased prevalence has been attributed to several contributing factors encompassing both lifestyle and genetics. Risk factors include overweight/obesity, inactivity, race, stage of development (hormonal influence), and sex (with females at greater risk). Children are also more likely to develop T2DM if their parents or siblings have it, but this may be related to lifestyle factors such as diet in addition to genetics. Children are more likely to have unhealthy dietary patterns if their parents do because the parents are typically responsible for purchasing the food and preparing the meals. There is evidence that risk is linked with genetic predisposition and fetal environment: children born to mothers who had gestational diabetes mellitus (GDM) during the pregnancy are more likely to develop T2DM.2-4 Early development of T2DM is a cause for concern because diabetes-related complications can impair quality of life or reduce life span if blood glucose levels are not controlled over time. Initially, children usually retain sufficient pancreatic function to overcome insulin resistance before developing T2DM, but they partition fat differently and tend to have higher triglyceride levels,2 which increase the risk of heart disease, stroke, and fatty liver. Over time, hepatic lipid deposition can lead to non-alcoholic fatty liver disease, which can progress to scarring and cirrhosis (see Chapter 16). Children are at risk of developing the same micro- and macrovascular complications as adults, including ocular changes, increased risk of fungal and bacterial infections, kidney damage, neuropathy, and impaired cognitive function. The American Diabetes Association (ADA) Standards of Medical Care in Diabetes recommend that even asymptomatic children be screened every 3 years starting at the age of 10 or when puberty occurs if they are overweight (.85th percentile or .120% expected weight for height) and have two or more additional risk factors from the following list: first- or second- degree relative with T2DM; of Latin, Asian, African American, or Native American descent; or gestational exposure to GDM.4 Since data on appropriate criteria for fasting plasma glucose and oral glucose tolerance tests in pediatrics are limited,5 the ADA recommends use of HbA1c.4 Pharmacological interventions in pediatrics are limited to Glucophage (metformin) and insulin. The American Academy of Pediatrics (AAP) recommends that all children with T2DM take Glucophage, reserving insulin use for children with poorly controlled blood glucose as evidenced by random blood glucose .250 mg/dL, an A1c .9%, ketoacidosis, or type 1 diabetes mellitus.6,7 While medications are effective, nutrition interventions are useful to improve blood glucose control and promote weight loss if necessary. Nutrition education and counseling must include the family to address environmental components. Caregivers require education on how to recognize and treat signs and symptoms of hypo- and hyperglycemia in addition to information about factors that can affect blood glucose levels such as illness, physical activity, diet, and medications. While there is no specific "diabetic" diet that children must follow, parents and caregivers should be educated about ways to increase physical activity and about healthy eating patterns that include whole grains, fruits, vegetables, and lean proteins. Key goals include achieving a healthy weight and stabilizing blood glucose levels.

Polycystic Ovarian Syndrome: More than Infertility Definition Polycystic ovarian syndrome (PCOS) is an endocrine problem affecting approximately 10% of women during their reproduc- tive years. PCOS can affect a woman's menstrual cycle, fertility, hormones, insulin production, heart, blood vessels, and appearance. Women with PCOS have these characteristics: • High levels of male hormones, also called androgens. This may cause excessive facial and body hair growth. • An irregular or no menstrual cycle. • In some cases, many small cysts (fluid- filled sacs) on their ovaries. PCOS is the most common hormonal reproductive problem in women of child- bearing age. Etiology The exact cause of PCOS is unknown. Women with PCOS frequently have a mother or sister with PCOS, but there is not yet enough evidence to say there is a genetic link for this disorder. The majority 484 Part 4 Nutrition Therapy of women with PCOS have insulin resistance with high circulating levels of insulin. It is possible that the ovaries react by making too many male hormones, called androgens. This can lead to acne, excessive hair growth, weight gain, and ovulation problems. Pathophysiology In women with PCOS, the ovary doesn't make all of the hormones it needs for any of the eggs to fully mature. They may start to grow and accumulate fluid. But no one egg becomes large enough. Instead, some may remain as cysts (see Figure 17.11). Since no egg matures or is released, ovulation does not occur and the hormone progesterone is not made. Without progesterone, a woman's menstrual cycle is irregular or absent. Also, the cysts produce male hormones, which continue to prevent ovulation. Researchers think that as women reach menopause, ovarian function changes and the menstrual cycle may become more normal. But even with falling male hormone levels, excessive hair growth continues, and male-pattern baldness or thinning hair gets worse after menopause. Clinical Manifestations These are some of the symptoms of PCOS: • Infrequent menstrual periods, no menstrual periods, and/or irregular bleeding • Infertility or inability to get pregnant because of not ovulating • Increased growth of hair on the face, chest, stomach, back, thumbs, or toes • Acne, oily skin, or dandruff • Pelvic pain • Weight gain or obesity, usually carrying extra weight around the waist • Type 2 diabetes • High cholesterol • High blood pressure • Male-pattern baldness or thinning hair • Patches of thickened and dark brown or black skin on the neck, arms, breasts, or thighs • Skin tags, or tiny excess flaps of skin in the armpits or neck area • Sleep apnea—excessive snoring and ces- sation of breathing at times while asleep Diagnosis There is no single test to diagnose PCOS. Diagnostic procedures include medical history, physical exam, serum levels of hormones and glucose, and an ultrasound that can document the appearance of polycystic ovaries. Treatment Because there is no cure for PCOS, it needs to be managed to prevent problems. Treatments are based on the symptoms each patient is having and whether she wants to conceive or needs contraception. Below are descriptions of treatments used for PCOS. Nutrition therapy. Weight management (see Chapter 12) is the first step in nutri- tion therapy for PCOS, with which obe- sity is common. Achieving an appropriate weight with a healthy diet and physical activity will help the body lower glucose levels and use insulin more efficiently, and may help restore a normal period. Even loss of 10% of her body weight can help make a woman's cycle more regular. Additionally, spacing of cycle and prevent endometrial problems. But progesterone alone does not help reduce acne and hair growth. Diabetes medications. The medicine metformin (Glucophage), which is used to treat T2DM, also helps with PCOS symp- toms. Metformin affects the way insulin regulates glucose and decreases testos- terone production. Abnormal hair growth will slow down and ovulation may return after a few months of use. Fertility medications. The main fertility problem for women with PCOS is the lack of ovulation. Even so, the partner's sperm count should be checked and the woman's tubes checked to make sure they are open before fertility medications are used. Clo- miphene (pills) and gonadotropins (shots) can be used to stimulate the ovary to ovu- late. PCOS patients are at increased risk for multiple births when using these medica- tions. In vitro fertilization (IVF) is sometimes recommended to control the chance of having triplets or more. Metformin can be taken with fertility medications and helps to make PCOS women ovulate on lower doses of medication. Medicine for increased hair growth or extra male hormones. If a woman is not trying to get pregnant there are some other medicines that may reduce hair growth. Spironolactone is a blood pres- sure medicine that has been shown to decrease the male hormone's effect on hair. Propecia, a medicine taken by men for hair loss, is another medication that blocks this effect. Both of these medi- cines can affect the development of a male fetus and should not be taken if pregnancy is possible. Other non-medical treatments such as electrolysis or laser hair removal are effective at getting rid of hair. A woman with PCOS can also take hormones to keep new hair from growing. Potential Complications Women with PCOS can be at an increased risk for developing several other condi- tions. Irregular menstrual periods and the absence of ovulation cause women to produce the hormone estrogen, but not the hormone progesterone. Without progesterone, which causes the endome- trium to shed each month as a menstrual period, the endometrium becomes thick, which can cause heavy or irregular bleed- ing. Eventually, this can lead to endome- trial hyperplasia or cancer. Women with PCOS are also at higher risk for diabetes, high cholesterol, high blood pressure, and energy and carbohydrate intake throughout the day and ensur- ing adequate protein sources are included at each meal and snack will assist with potential blood glucose abnormalities. Birth control pills. For women who don't want to become pregnant, birth control pills can regulate menstrual cycles, reduce male hormone levels, and help to clear acne. However, the birth control pill does not cure PCOS. The men- strual cycle will become abnormal again if the pill is stopped. Women may also think about taking a pill that only has progesterone, like Provera, to regulate the menstrual Figure 17.11 Polycystic Ovarian Syndrome Normal ovary Polycystic ovary Source:

Major Metabolic Effects Effect on Blood Effect on Blood Effect on Blood Hormone Glucose Fatty Acids Amino Acids Control of Secretion Effect on Muscle Protein Major Stimuli for Secretion Blood glucose Blood amino acids Blood glucose Blood amino acids Primary Role in Metabolism Primary regulator of absorptive and post- absorptive cycles Regulation of absorptive and post- absorptive cycles in concert with insulin; protection against hypoglycemia Provision of energy for emergencies and exercise Mobilization of metabolic fuels and building blocks during adaptation to stress Promotion of growth; normally little role in metabolism; mobilization of fuels plus glucose sparing in extenuating circumstances Insulin ↓ ↓ ↓ ↑ ↑ ↑ ↓ ↑ 1 Glucose uptake 1 Triglyceride 1 Glycogenesis synthesis 1 Amino acid uptake No effect No effect 1 Protein synthesis 2 Protein degradation No effect No effect ↓ 1 Protein degradation ↑ 1 Protein synthesis 2 Protein degradation 1 Synthesis of DNA and RNA 2 Lipolysis ↑ ↑ 2 Glycogenolysis 2 Gluconeogenesis Glucagon Epinephrine Cortisol Growth hormone 1 Glycogenolysis 1 Lipolysis 1 Gluconeogenesis 2 Triglyceride 2 Glycogenesis ↑ ↑ 1 Glycogenolysis 1 Lipolysis 1 Gluconeogenesis 2 Insulin secretion 1 Glucagon secretion ↑ ↑ 1 Gluconeogenesis 1 Lipolysis 2 Glucose uptake by tissues other than brain; glucose sparing ↑ ↑ 2 Glucose uptake by 1 Lipolysis muscles; glucose sparing 1 1 ↑ Protein degradation ↓ Amino acid uptake Sympathetic stimulation during stress and exercise Stress Deep sleep Stress Exercise Hypoglycemia Note: Up arrows (↑) and plus signs (1) indicate increases; down arrows (↓) and minus signs (2) indicate decreases.

Table on 478

Carbohydrate Counting Carbohydrate counting is a meal planning approach that concentrates on the total amount of carbohydrate eaten at meals and in snacks. It is based on research demonstrating that consistent intake of a wide variety of carbohydrates results in similar post-prandial glucose responses. Awareness of total carbohydrate intake and distribution has also been shown to improve metabolic control. The American Diabetes Association (ADA) states that monitoring carbohydrate remains a significant tactic in realizing glycemic control. The ADA also states that sucrose-containing foods can be used as other carbohydrates in the meal plan or, if added to the meal plan, balanced with insulin or other glucose-lowering medications. Carbohydrate Choices There is no fixed quantity of carbohydrate that is recommended for everyone. The amount of carbohydrate is established in consultation with the individual with diabetes. Amounts can then be adjusted based on blood glucose monitoring results and what is determined to be reasonable in context of the indi- vidual's lifestyle. A case example illustrating how carbohydrate choices are established follows. Case Scenario: Mike, a 24-year-old male, has T1DM. He is 5'10" and weighs 165 lbs. Using his diet history, you determine that he should consume approximately 55% of his kcal from CHO. Estimated energy requirement (EER): 2200-2400 kcal/day Step One: Take EER and multiply by 55%. 2200 3 0.55 5 1210 kcal from CHO Step Two: 1210 kcal 4 4 5 302 g of CHO Step Three: Determine the number of CHO choices for a 24-hour period: 302 g 4 15 g per choice 5 20. This is the number of CHO choices for Mike to consume in the 24-hour period. This amount will be adjusted according to his weight, hunger, and physical activity levels. Step Four: Divide the CHO choices among meals and snacks so that Mike will know the amount of rapid-acting insulin he should use at each meal. After he has stabilized and has records from his self-monitoring of blood glucose, the amount of insulin required for each carbohydrate choice can be fine- tuned. This is discussed below. IInsulin-to-Carbohydrate Ratio The insulin-to-carbohydrate ratio is a mechanism for determin- ing insulin dosage based on carbohydrate intake. Generally, 1 unit of rapid-acting insulin is taken for every 10-15 g of carbohydrate. This is used as a starting point, then adjusted based on SMBG records. The "500 rule" is used to calculate the initial insulin-to-carbohydrate ratio. "500" is divided by an individual's total daily dose of rapid-acting insulin. ("450" is used for regular insulin.) For example: If the total daily insulin dose is 50 units of rapid-acting insulin, 500 is divided by 50 to equal 10 grams of carbohydrate covered by each unit of rapid-acting insulin. The insulin-to-carbohydrate ratio is 1 unit of insulin for every 10 g of carbohydrate. Correction Factor If necessary, a correction factor can be used with the insulin-to-carbohydrate ratio to assist in returning blood glucose levels to the target range. Blood glucose values will indicate whether this is necessary. One unit of rapid- acting insulin is given for every 50 mg/dL that blood glucose rises above 150 mg/dL. For example, if blood glucose is 151-200 mg/dL, 1 unit of insulin is added; if blood glucose is 201-250 mg/dL, 2 units are added; and blood glucose levels of 251-300 mg/dL would require the addition of 3 units of insulin. Blood glucose levels of 300 mg/dL and above require the addition of 4 units of insulin. Mealtime Insulin In summary, the mealtime insulin dosage equals the insulin-to- carbohydrate ratio plus the correction factor (if needed)

Table on 502

Technique Benefit Recommendations Comments Self-monitoring of blood glucose (SMBG) A1c • Allows patients to individualize response to therapy • Useful in preventing hypoglycemia • Useful in adjusting medications, nutrition therapy, and physical activity • Allows measurement of average glycemia over preceding 2-3 months MDI or insulin pump: Pre-/post- prandial; bedtime; prior to exercise; suspect low blood glucose; after treatment for low blood glucose. Non-insulin users: May be recommended to guide treatment decisions and assist with patient self- management. Twice yearly when meeting treatment goals; quarterly when treatment changes • Accuracy is instrument and user dependent • Evaluate patients' monitoring techniques initially and subsequently at regular intervals • Regularly evaluate patients' ability to translate and use SMBG data to adjust food intake, exercise, or pharmacological therapy to achieve specific glycemic goals • Regular A1c testing allows detection of departures from target management goals Glycemic Indicator Normal Goal1 70-130 mg/dL (5.0-7.2 mmol/L) Levels established if A1c target goals are not met OR ,180 mg/dL Levels established if A1c target goals are not met OR ,180 mg/dL ,7% Goal in Pregnancy #95 mg/dL (5.3 mmol/L) #140 mg/dL (6.7 mmol/L) #120 mg/dL (6.7 mmol/L) #6% Preprandial ,100 glucose (,6.7 1-hour ,140 post-prandial (,7.2 glucose 2-hour post- ,100 prandial (,6.7 A1c2 4-6% m Mean Plasma Glucose A1c (%) (mg/dL) (mmol/L) Mean Plasma Glucose Note: 1For non-pregnant adults. Different treatment goals may be war- ranted by individuals with comorbid diseases, very young children, older adults, and others with unusual conditions or circumstances. 2Primary target for glycemic goals. Source: Adapted from American Diabetes Association. Standards of Medi- cal Care in Diabetes—2014. Diabetes Care. 2014; 37(Suppl 1): S14-S79. 6 7 8 9 10 11 12 126 154 183 212 240 269 298 7.0 8.6 10.2 11.8 13.4 14.9 16.5

Tables on 503

In its active form, insulin consists of two polypeptide chains (a total of 51 amino acids) linked by disulfide bridges between cysteine molecules. When the chains separate, it becomes inactive. lipolysis, which provides additional substrate to meet energy requirements. The glucagon-like-peptides 1 and 2 (GLP-1 and GLP-2) are derived from the precursor for glucagon and act to stimu- late the action of insulin and inhibit that of glucagon. Because GLP-1 and GLP-2 have a very short half-life, their action potential is limited. Nonetheless, maximizing their function allows for an additional path to control abnormal blood glu- cose levels, and thus has recently been a focus in the devel- opment of medications such as exenatide (Byetta), discussed later in this chapter. Pathophysiology of the Endocrine System As mentioned previously, endocrine disorders are the result of hyposecretion or hypersecretion of hormones, or of hyporesponsiveness of target organs.1,2 Table 17.4 outlines the most common causes of endocrine dysfunction. Primary hyposecretion occurs when an endocrine organ releases an inadequate amount of hormone to meet physi- ological needs. Secondary hyposecretion occurs when secre- tion of a tropic hormone is inadequate to cause an endocrine organ to secrete adequate amounts of a hormone. For instance, if the thyroid gland produces inadequate amounts of thyroid hormone, this would be considered primary hyposecretion, whereas inadequate production of thyroid hormone that is caused by insufficient secretion of a tropic hormone such as thyroid-stimulating hormone (TSH) is secondary hyposecre- tion. The interrelationship of the various hormones makes diagnosis of hormone deficiency quite complex. Evaluation of multiple lab values may assist in differentiating between primary and secondary deficiencies. In a primary thyroid hormone deficiency, for example, thyroid hormone would be low, but TSH levels would be high; in secondary thyroid hormone deficiency, both thyroid hormone and TSH levels would be abnormally low.2 Hypersecretion disorders can also be primary or second- ary. When an endocrine gland is secreting abnormally high amounts of a hormone due to a primary disorder, the tropic hormone will be at unusually low levels. When hypersecre- tion is secondary (to elevated tropic hormone levels), plasma concentrations of both hormones will be elevated.2 Hyporesponsiveness of the target organ will cause the same symptoms as hyposecretion, but hormone levels will be normal or high instead of low. Most cases of hyporesponsive- ness are caused by a lack or deficiency of hormone receptors on the target cells.2 An example of this type of disorder is type 2 diabetes mellitus.

Too little hormone secreted by the endocrine gland (hyposecretion)1 • Increased removal of the hormone from the blood • Abnormal tissue responsiveness to the hormone ◆ Lack of target cell receptors ◆ Lack of an enzyme essential to the target cell response • Too much hormone secreted by the endocrine gland (hypersecretion)1 • Reduced plasma-protein binding of the hormone (too much free, biologically active hormone) • Decreased removal of the hormone from the blood ◆ Decreased inactivation ◆ Decreased excretion

Type 1 Diabetes Mellitus Historically, terminology used to classify the different types of diabetes has changed (see Box 17.1). In order to prevent individuals from being classified by treatment modality rather than disease characteristics, the terms insulin-dependent diabetes mellitus (IDDM), juvenile diabetes, brittle diabetes, non-insulin-dependent diabetes mellitus (NIDDM), adult- onset diabetes, or borderline diabetes should not be used. Epidemiology Type 1 diabetes mellitus (T1DM—see chapter endnote 2) accounts for 5%-10% of all diagnosed cases of diabetes.5 While this form of diabetes develops most frequently in children and adolescents, it is increasingly diagnosed later in life, even in individuals in their 80s and 90s.6 Gender distribution of T1DM is equal. Etiology Immune-mediated type 1 diabetes mellitus results from a cell-mediated autoimmune response causing a gradual decline in b cell mass within genetically susceptible individuals. The primary gene for type 1 DM is located in the HLA region on chromosome 6. Polymorphisms in the HLA complex account for 40%-50% of the genetic risk of developing type 1 DM, but more than 20 different gene associations have been linked to risk for this disease. The genetic component of T1DM supports the increased risk of relatives of individuals with T1DM but relative risk is overall fairly low: 3%-4% if the parent has T1DM and 5%-15% in a sibling.3 Determining the environmental agent that initiates the autoimmune response has been difficult because of the time lapse between exposure and the development of DM, but research suggests that the interaction of several environmental factors with genes contributes to the onset of the auto- immune response. Potential triggers include viruses and gluten. Other environmental connections include vitamin D levels and infant feeding practices including length of breastfeeding and exposure to cow's milk proteins.8 There are several important ongoing prospective studies that hopefully will provide addi- tional evidence for these environmental triggers.9 Some forms of T1DM have no known cause and are referred to as fulminant T1DM. Individuals with this form of diabetes have a more immediate and complete destruction of the b cells, produce no insulin, and are prone to ketoacidosis, but have no evidence of autoimmunity. Individ- uals with T1DM who fall into this category represent a very small minority, and most are of African or Asian ancestry.10 Pathophysiology and Clinical Manifestations As dis- cussed earlier in this section, T1DM is characterized by the deficiency of insulin due to destruction of pancreatic b cells, resulting in the inability of cells to use glucose for energy.3 By the time clinical symptoms occur, 60%-80% of b cells have been destroyed. Cells that produce glucagon, somatostatin, and pancreatic polypeptide are typically conserved but may be redistributed within the islets. As shown in Figure 17.10, the acute consequences of an insulin deficit are numerous and potentially fatal. When glucose cannot enter cells, two things happen: plasma glucose levels rise (hyperglycemia, #1 in Figure 17.10) and cells starve. This signals an increase in gluconeogenesis in the liver as well as stimulation of glycogenolysis. These further contribute to the hyperglycemic state. To compensate for the hyperglycemia, excess glucose is lost in the urine because the kidneys can filter only so much glucose from the blood. As a result, glycosuria (#2) and frequent urination (polyuria, #3) occur. Loss of fluid stimulates the thirst mechanism and leads to polydipsia (#10). Cells dependent on glucose for energy have none available. In turn, the body responds to this emergency by promoting hunger (polyphagia, #11).3 As the insulin deficiency persists, production of additional hormones (catecholamines, cortisol, glucagon, and growth hormone) increases, leading to lipolysis (Figure 17.10, #12). As the body breaks down fat stored in adipose tissue, the resulting fatty acids are transformed into keto acids in the liver (#13). In the non-diabetes state, keto acids can be used for energy by muscle and brain cells. As increased production of keto acids occurs, pH falls (7.3 to 6.8), and ketone bodies are secreted in the urine. Meta- bolic acidosis (#14) develops as bicarbonate concentration is reduced, and ketoacidosis results. The body tries to off- set metabolic acidosis through deep, labored respirations (Kussmaul respirations, #16).2,3 As total body water decreases, potassium, sodium, mag- nesium, and phosphorus are also lost. Serum levels of these ions may be normal or elevated due to decreased fluid volume in the body (hypovolemia, #5 in Figure 17.10). Hypovolemia also accounts for increased hematocrit, hemoglobin, protein, white blood cell count, creatinine, and serum osmolality. Hypovolemia and muscle catabolism are the causes for considerable, imminent weight loss in persons with ketoacidosis (#17), and often present at diagnosis of T1DM. Hypovolemic shock can lead to death if left untreated (#6 and #7).

Type 2 Diabetes Mellitus Epidemiology In the United States and worldwide, about 90%-95% of all diagnosed cases of diabetes are type 2 diabetes mellitus (T2DM). T2DM occurs most frequently in adults, but is being diagnosed with increasing frequency in children and adolescents as well (see Box 17.3).5 Gender distribution of T2DM is equal, but prevalence increases with age. Other risk characteristics for T2DM include obesity, family history, history of gestational DM, impaired glucose metabolism, and physical inactivity. T2DM is not an equal-opportunity disease: older adults and persons of color are disproportionately affected. The prevalence of diabetes (diagnosed and undiagnosed) is 10.2% for non-Hispanic whites 20 years or older; 18.7% for all non- Hispanic blacks age 20 and older; 11.8% for Hispanics/Latinos; 16.1% for American Indians and Alaska natives; and 8.4% for Asian Americans.11 Areas of the world with a significant prevalence of diabetes include India, Latin America and the Caribbean, the Middle East, and China. Etiology T2DM evolves from a combination of abnormal insulin secretion and insulin resistance. This condition is considered to be polygenic, with multiple factors contribut- ing to its development. Primary environmental factors include obesity, poor nutrition, and physical inactivity. Identifiable gene defects have been found in most families with this pattern of diabetes. Obesity—body fat distribution in particular—also appears to play a role in development of T2DM. Central body adiposity seems to increase the degree of insulin resistance. Physical inactivity increases risk of T2DM unrelated to body weight, whereas exercise seems to reduce risk of T2DM by enhancing whole-body insulin sensitivity. High birth weight also appears to increase the risk for T2DM during adulthood.3 Pathophysiology Whereas T1DM results from lack of insulin caused by destruction of b cells, individuals with T2DM produce insulin, but their tissues are insulin resistant. This increases the need for insulin, so the pancreas increases produc- tion. Over time the pancreas is not able to maintain such high insulin production levels.3 Consequently, two metabolic defects are observed in individuals with T2DM: insulin resistance and relative insulin deficiency. Although insulin resistance develops many years before onset of diabetes in individuals with predis- position to T2DM, clinical onset is correlated with the dimin- ishing pancreatic release of insulin.3 T2DM is typified by peripheral insulin resistance with an insulin secretory defect that varies in severity. Insulin resistance is caused by a cell-receptor defect resulting in the body's inability to use insulin. When cells cannot respond to insulin by translocating glucose transporters to their outer membrane, they are unable to take up glucose from the blood for fuel. Since insulin normally serves to inhibit glycogenolysis and gluconeogenesis when blood glucose is high, defective insulin secretory response results in excessive hepatic gluconeogenesis. For T2DM to manifest, both defects must be present. At first, post-prandial glucose levels rise due to the inability of the cells to utilize glucose; subsequently, hepatic gluconeogenesis steps up to compensate for the lack of glucose within cells, resulting in fasting hyperglycemia.3 Metabolic Syndrome Another condition related to insulin resistance is metabolic syndrome, which shares some characteristics with T2DM. Central obesity and insulin resistance are significant contributing features, along with atherosclerotic risk factors including dyslipidemia and hypertension.12 Diagnostic criteria are outlined in Chapter 13. Metabolic syndrome places individuals at increased risk for coronary artery disease. Treatment of metabolic syndrome is multifaceted and includes diet, exercise, and pharmacologic therapy including statins, fibrates, angiotensin-converting enzyme (ACE) inhibitors, and thiazolidinediones. Over one-third of the U.S. population over age 20 meet the criteria for metabolic syndrome.13 Clinical Manifestations While onset of T1DM is sudden, onset of T2DM is insidious. Many individuals will be asymptomatic for as long as 6-10 years but present with complications associated with diabetes. For example, an optician may detect retinopathy during a visit provoked by blurred vision. The estimate that as many as one-third of all individuals with T2DM are undiagnosed reinforces the need for screening of individuals at high risk. Criteria for testing and screening for diabetes in asymptomatic, undiagnosed adults are listed in Box 17.2, and one of these criteria—polycystic ovarian syndrome—is discussed further in Box 17.4.

Short-Term Illness Everyday maladies such as colds, fever, nausea, vomiting, and diarrhea can cause havoc with glycemic control for individuals with diabetes. If hyperglycemia is left untreated, DKA or HHS can develop. Treatment includes sup- plemental insulin; replacement fluids, electrolytes, and glu- cose; blood glucose monitoring; and urine testing for ketones. Sometimes medical intervention is necessary. Nutrition Assessment Standard nutrition assessment should focus on fluid, food, and carbohydrate intakes; insulin dosages and delivery methods; SMBG records; urine ketone levels; and knowledge regarding self-care. Nutrition Diagnosis Nutrition diagnoses associated with short-term illness may include inadequate fluid intake, altered GI function, and inability or lack of desire to manage self-care. Nutrition Intervention Individuals with diabetes should be provided with a list of carbohydrate-containing foods that are tolerated during acute illness and are easy to digest. Further- more, for illnesses lasting less than 24 hours, the following guidelines are recommended:7 • Take usual insulin doses during acute illness. Insulin is still necessary, and insulin needs may even increase because fever, infection, or stress can trigger release of counter-regulatory hormones. • Monitor blood glucose and test for ketones at least four times a day, before each meal and at bedtime. Additional insulin is needed if blood glucose .240 mg/dL and mod- erate to large amounts of ketones are present. • Drink a large glass of liquid (e.g., water, tea, broth) every hour. Small sips of 1-2 tbsp every 15-30 minutes should be consumed if nausea or vomiting is present. A primary care provider should be notified if vomiting persists longer than 6 hours. • If regular foods are not tolerated, replace meals with small amounts of liquid or soft carbohydrate-containing foods eaten every 3-4 hours. Consume 3-4 carbohydrate servings (45-60 grams of carbohydrate) of foods such as regular soft drinks (do not use sugar-free soft drinks), soup, juices, Jell-O®, and ice cream. • Contact a primary care provider if illness continues .24 hours or if unable to eat regular foods for .24 hours. • Call a physician if any of the following DKA symptoms develop, especially in children: moderate to large amount of ketones in urine with elevated blood glucose levels; fruity-smelling breath; severe nausea; vomiting; diarrhea; abdominal pain; or rapid breathing. Long-Term Complications of Hyperglycemia Diabetes is a complicated, chronic metabolic disorder that requires attention to issues beyond glycemic control.3,7,30 Long-term hyperglycemia from either T1 or T2DM results in microvascular and macrovascular complications that substantially increase morbidity and mortality associated with the disorder and reduce quality of life. These compli- cations typically occur 15-20 years after onset of diabetes. Occurrence and rate of development of chronic complica- tions of diabetes can be reduced, however, as demonstrated by the longitudinal DCCT, EPIC, UKPDS, ADVANCE, and ACCORD trials. Optimal glycemic control results in signifi- cantly lower A1c; reductions in incidence and rate of progres- sion of retinopathy, nephropathy, and neuropathy; and improved cardiovascular outcomes.7,21,22 Macrovascular Complications: Cardiovascular Disease Cardiovascular lesions are the most common cause of prema- ture death in individuals with diabetes. About 65% of deaths among individuals with diabetes are due to heart disease or stroke, and adults with diabetes have heart disease-related death rates about two to four times higher than those of adults without diabetes.24,30 Hyperglycemia makes all blood vessels prone to endo- thelial damage, leading to thickening and changes in compo- sition of the subendothelial (intimal) layer. Hyperglycemia also directly affects the structure of the basement membrane of the vessels. This thickening and decreased flexibility of the vessel increase blood pressure and contribute to the accelera- tion of atherosclerosis seen in diabetes. In larger vessels, the intima can enlarge significantly and amass both intracellular lipid and extracellular lipid, necrotic debris, and calcium. This results in an advanced, complex atherosclerotic lesion. Ulcer- ation of the lesion (plaque) into the lumen can also occur, leading to embolization, thrombus formation, or both.30 Diabetes is an independent risk factor for macrovascular disease in addition to the common coexisting risk factors of hypertension and dyslipidemia (see Chapter 13). Hyperten- sion is not only a major risk factor for cardiovascular disease (CVD), but also a complication for microvascular complica- tions of DM such as retinopathy and nephropathy. Hyper- tension is often the consequence of underlying nephropathy in individuals with T1DM. In T2DM, hypertension may manifest as part of metabolic syndrome, which is accompa- nied by high rates of CVD. Prompt and aggressive medical management including pharmacological intervention is rec- ommended for all patients with blood pressure higher than 140/80 mmHg.7 Hypertension can be alleviated by increas- ing physical activity and consumption of fruits, vegetables, and low-fat dairy products; by decreasing sodium intake and body weight (when indicated); and by avoiding exces- sive alcohol intake. Dyslipidemia interventions (discussed in Chapter 13) should focus primarily on reducing LDL choles- terol to ,100 mg/dL using MNT, increasing physical activity, and facilitating weight loss and smoking cessation.7 Nephropathy Nephropathy occurs in 20%-40% of individ- uals with diabetes and is the single leading cause of chronic kidney disease (CKD)—kidney failure that must be treated with dialysis or transplantation (see Chapter 18).5 Diabetes is the cause of 44% of new cases of CKD. Hyperglycemia results in changes in the structure of the blood vessels of the glomerulus, the functioning unit of the kidney, which is comprised of a tuft of capillaries. Changes in the capillary structure result in increased permeability and decreased filtering ability. The earliest stage of nephropa- thy is persistent albuminuria (albumin in the urine) in the range of 30-299 mg/24 hours (microalbuminuria). Onset of microalbuminuria and progression to macroalbumin- uria (.300 mg/24 hours) in individuals with diabetes can be delayed by intensive diabetes management (defined as

achieving near-normoglycemia). Optimal glycemic and blood pressure control are the initial interventions for individuals with albumin excretion of ,30 mg/24 hours. For those with higher levels of microalbuminuria, either ACE inhibitors or ARBs are recommended. Restriction of dietary protein is not recommended because it does not improve glycemic control or slow the decline of the glomerular filtration rate.7 Retinopathy Retinopathy is the most frequent cause of new cases of blindness in adults, and prevalence of retinopathy is strongly associated with duration of diabetes.3,30 Though the mechanisms are not completely understood, the damage to the eye appears to be directly related to hyperglycemic damage to its blood vessels. The eye is highly vascularized and has a sig- nificant oxygen demand. Changes in the blood vessels and the accumulation of sorbitol appear to be the major factors associ- ated with retinopathy. In addition, other eye ailments, including glaucoma and cataracts, occur earlier in individuals with diabe- tes. Hypertension, an established risk factor for development of macular edema, is also associated with the development of retinopathy. Progression of retinopathy can be decreased by glycemic control and lowering of blood pressure.30 Nervous System Diseases Approximately 50% of individ- uals with diabetes have some form of nervous system damage that causes impaired sensation or pain in the feet or hands, slowed digestion of food in the stomach, carpal tunnel syn- drome, impaired wound healing, motor dysfunction, and/or even bone fracture. It is once again chronic hyperglycemia that leads to these complications. The accumulation of abnor- mal substances such as sorbitol and glycated proteins results in cellular damage, disrupting the normal nervous system pathways. As with retinopathy, not all mechanisms of diabetic neuropathy are understood.30 Peripheral neuropathy causes pain and then loss of sen- sation in the feet and hands. Because of this loss of sensa- tion, injuries to limbs may go unrecognized, which may lead to consequences such as ulcerations, infection, and even the need for amputation. The significance of autonomic neuropathy, a serious and common complication of diabetes, is often underappreciated. It can involve one or more mechanisms of the autonomic nervous system. Autonomic neuropathy commonly coexists with other peripheral neuropathies and other complications of diabetes. It may affect many organ systems throughout the body, including the gastrointestinal tract, genitourinary tract, and cardiovascular system. Gastrointestinal (GI) distur- bances are common and can occur along any section of the GI tract. Gastroparesis, delayed gastric emptying, results from damage to the vagus nerve, which controls peristalsis. It can cause anorexia, nausea, vomiting, early satiety, post-prandial bloating, and erratic glycemic control. Box 17.5 describes nutrition therapy for treatment of gastroparesis. Constipation is the most frequent lower GI symptom of autonomic neu- ropathy, but can alternate with episodes of diarrhea. Bladder and/or sexual dysfunction are common genitourinary tract disturbances associated with autonomic neuropathy and may manifest as recurrent urinary tract infections, pyelonephritis (injury to kidneys caused by bacterial infection), or incon- tinence. Males and females may suffer sexual dysfunction. Cardiovascular autonomic neuropathy (CAN) is considered 508 Part 4 Nutrition Therapy the most clinically important form of autonomic neuropathy. It may manifest through resting tachycardia (.100 bmp), ortho- static hypotension (a fall in systolic blood pressure .20 mmHg upon standing), or increased risk of silent heart disease.30 Nutrition Therapy for Long-Term Complications of Hyperglycemia Nutrition problems related to the medical complications associated with diabetes include inappropriate intake of types of carbohydrates; inconsis- tent carbohydrate intake; inadequate fiber intake; altered GI function (gastroparesis); altered nutrition-related laboratory values; food-medication interaction; underweight; food- and nutrition-related knowledge deficit; harmful beliefs/attitudes about food- or nutrition-related topics; not ready for diet/ lifestyle change; self-monitoring deficit; undesirable food choices; physical inactivity; and inability or lack of desire to manage self-care. Many of these problems are common to diabetes patients with or without complications, and should be addressed using the nutrition intervention and monitor- ing strategies for hyperglycemia discussed throughout the "Diabetes Mellitus" section of this chapter. Additional strat- egies for addressing nutrition problems that many diabetic patients experience are covered throughout this text and can be incorporated into the nutrition intervention. For example, Chapter 13 provides details on lipid management, which is an important component of preventing heart disease for individuals with diabetes. Chapter 14 provides suggestions for nausea, vomiting, and delayed gastric emptying. Gestational Diabetes Mellitus Definition Gestational diabetes mellitus (GDM) is a form of glucose intolerance first diagnosed during pregnancy.3,7 Epidemiology Approximately 2%-10% of all pregnancies are complicated by GDM, and women who develop GDM have a 35%-60% chance of developing diabetes in the next 5-10 years.5 Women at risk for GDM have the following characteristics: • Obesity (BMI .30.0) • Personal history of GDM • Glycosuria • Strong family history of diabetes (first-degree relative) • Prior poor obstetrical outcome (stillbirth, birth defects, or baby .9 lbs) • Member of a high-risk ethnic group (Hispanic, African American, Native American, South or East Asian, Pacific Islander) Etiology During the second or third trimesters of preg- nancy, metabolic alterations occur to meet maternal and fetal demands for energy and nutrients. These alterations include changes in both insulin secretion and glucose, amino acid, and lipid metabolism. Although most women with GDM have nor- mal glucose tolerance after delivery, their likelihood of devel- oping GDM in subsequent pregnancies and T2DM later in life is increased. Increasing physical activity and reducing post- partum weight gain can reduce risk of subsequent diabetes.3,7 Pathophysiology GDM is pathophysiologically similar to T2DM. Islet cell function abnormalities or peripheral insulin resistance are thought to decrease insulin secretory response

he endocrine system is more of a complex functional system than an anatomical system. Endocrine glands that make up the endocrine system are not attached anatomically, but scattered all through the body. All the same, these glands make up a system in a functional sense, since their regulatory activities are often interdependent and must be closely coordinated. Endocrine glands carry out their functions by secreting hormones (chemical messengers) into the blood, and numerous interactions occur between the various glands (see chapter endnote 1). A single endocrine gland may secrete several hormones: the pituitary gland secretes six hormones that have distinct functions and are under different control mechanisms. A single hormone may be secreted by more than one endocrine gland; for example, somatostatin is secreted by both the hypothalamus and the pancreas. Some endocrine organs, like the anterior pituitary, exclusively secrete hor-mones, whereas other endocrine organs perform additional functions. The testes, for example, both produce sperm and secrete testosterone.1 Once released into the blood, hormones travel to tar- get organs—the intended recipients of the chemical "mes- sage." A single hormone can have more than one type of target organ and thus can generate more than one type of effect. Vasopressin acts as a vasoconstrictor throughout the

body in addition to promoting H2O reabsorption by kidney tubules. Some chemical messengers may function as a hormone or neurotransmitter depending on the sources and mode of delivery to the target cell. Norepinephrine is secreted as a hormone by the adrenal medulla and released as a neurotransmitter from sympathetic post-ganglionic nerve fibers. Some single hormones have assorted target- cell types and are capable of coordinating and integrating activities of various tissues toward a common end. Such is the effect of insulin on muscle, liver, and fat in the storage of nutrients after absorption.1 Secretion rates of specific hormones fluctuate in a cyclic pattern over time, providing chronological synchronization of function. Additionally, some hormones have a diurnal vari- ation, meaning that their levels fluctuate during the waking hours. Reproductive cycles, such as the menstrual cycle, are managed by endocrine hormones. Single target cells may be influenced by more than one hormone. Some cells contain an assortment of receptors for interacting in different ways with different hormones. Insulin promotes conversion of glu- cose into glycogen in liver cells by stimulating one particular hepatic enzyme, whereas glucagon activates another hepatic enzyme to enhance degradation of glycogen into glucose in liver cells. Specific functions of major hormones are listed in Table 17.1.

control. For individuals not meeting glycemic goals, or whose therapy has changed, A1c testing should be performed quar- terly.7 The A1c values are used to calculate the estimated aver- age glucose (EAG), a relatively new measure that is becoming a routine component of biochemical assessment in diabetes. Self-Monitoring of Blood Glucose Daily home glucose monitor- ing records the individual's glucose level at the very moment the measurement is taken. Information provided by self- monitoring of blood glucose (SMBG) can assist in adjusting daily eating patterns and medications as necessary to maintain glycemic control. SMBG is also useful in identifying patterns and the ways in which food, exercise, or other factors affect glycemic control. Adjustments to an individual's treatment pro- gram can be made immediately in order to prevent hyperglyce- mia, hypoglycemia, and long-term complications of diabetes. A typical SMBG test includes a drop of blood obtained via a finger prick that is then analyzed using a blood glucose meter. Frequency and timing of SMBG should be deter- mined by the specific needs and goals of the individual with diabetes and the health care team. As a means to monitor for asymptomatic hypoglycemia and hyperglycemia, daily SMBG is particularly valuable for all individuals with dia- betes. For individuals using MDI or pump therapy, SMBG is recommended prior to meals and snacks, occasionally post- prandially, prior to exercise, when hypoglycemia is suspected, or to evaluate treatment of hypoglycemia.7 Accuracy of SMBG is instrument and user dependent. For this reason, the patient's monitoring techniques should be assessed at the onset and at regular intervals thereafter. Patients should also be taught how to use SMBG data to modify food intake, exercise, and pharmacological therapy in order to realize individual glycemic goals.7 Characteristics to consider when choosing a meter include light, sound effects, size, memory, and cost of test strips.26 Continuous Glucose Monitoring Continuous glucose moni- toring uses a device that communicates with a sensor placed right under the skin (see Figure 17.12D). The sensor trans- mits the blood glucose reading to the receiver device, which is worn around the waist—similar to a pager. This allows for continual reading of blood glucose levels every 5 minutes. It is not meant to replace SMBG but does provide a more detailed picture of blood glucose fluctuations and can help direct more detailed insulin prescriptions. Testing for Ketones Ketones are produced as a by-product of lipolysis (see "Pathophysiology and Clinical Manifestations" section above). Ketones in the blood can lead to serious and life-threatening acid-base disturbances. Ketones can be mea- sured by using a special urine test strip or by certain blood glucose meters. Urine should be tested for the presence of ke- tones regularly during periods of illness, when insulin pumps fail, or when insulin is not taken. In individuals with T1DM, urine ketones should be tested when blood glucose is consis- tently over 300 mg/dL.7,27 Other Testing In addition to monitoring glycemic control, other parameters that should be monitored include lipids and blood pressure. Total cholesterol, low-density lipopro- teins (LDL-cholesterol), high-density lipoproteins (HDL- cholesterol), and triglycerides should be monitored annually

or more frequently as needed. The accuracy of these tests is dependent upon an overnight fast. Goal values are as follows:14 • LDL-cholesterol: ,100 mg/dL • HDL-cholesterol: .40 mg/dL (men); .50 mg/dL (women) • Triglycerides: ,150 mg/dL7 Physical Activity For most individuals with diabetes, the following are benefits of physical activity:7 • Improved glycemic control (A1c) • Improved blood lipids and blood pressure, with subse- quent lower cardiovascular risks and overall mortality • Positive impact on metabolic abnormalities characteristic of T2DM • Prevention or delay of onset of T2DM for individuals at high risk for developing diabetes or with prediabetes • Reduced risk of development of cardiovascular disease, since physical inactivity and diabetes are independent risk factors for it • Improved coping and stress management and reduced feelings of depression • Improved physical fitness and functional capacity • Enhanced quality of life Physical activity recommendations are as follows: • "Children with diabetes or prediabetes should be encour- aged to engage in at least 60 minutes of physical activity each day. • Adults with diabetes should be advised to perform at least 150 minutes/week of moderate-intensity aerobic activity (50%-70% of maximum heart rate), spread over at least 3 days/week with no more than 2 consecutive days without exercise. • In the absence of contraindications, adults with type 2 dia- betes should be encouraged to perform resistance training at least twice per week."7 Nutritional Implications Both hypoglycemia and hyper- glycemia are acute risks of exercise. Hypoglycemia can occur during exercise that lasts longer than 1 hour, and for up to 24 hours after unusually strenuous, prolonged, and/or spo- radic exercise. Blood glucose levels should be monitored, and carbohydrates should be increased and/or insulin adjust- ments should be made. In general, if pre-exercise glucose is ,100 mg/dL, extra carbohydrate will be needed. In those individuals whose diabetes is poorly controlled (underinsu- linized) and who are ketotic, exercise can cause or worsen hyperglycemia. When insulin is deficient, the rise in counter- regulatory hormones that takes place during exercise causes an increase in hepatic glucose production and free fatty acids. Cellular uptake of glucose is minimal, resulting in both hyper- glycemia and increased production of ketones.7 Nutrition Assessment Self-management records should be evaluated to determine how blood glucose levels are affected by carbohydrate intake before and after exercise as well as insulin administration.

BOX 17.5 CLINICAL APPLICATIONS Risk Factors for and Treatment of Complications of Diabetes Mellitus Short-Term Complications Complication/Symptoms1 Hyperglycemia Symptoms: Polyuria, polydipsia, blurred vision, polyphagia, weight loss, fatigue, low energy, delayed healing, irritability Dawn phenomenon Symptom: Unexplained fasting hyperglycemia in A.M. Ketoacidosis Symptoms: Nausea and/or vomiting; stomach pain, fruity (acetone) breath, heavy (or Kussmaul) breathing, mental status change Hyperglycemic hyperosmolar syndrome Symptoms: Polyuria, polydipsia, polyphagia, weight loss; symptoms persist and worsen over several days or as hydration status worsens Mild hypoglycemia Symptoms: Trembling, nervousness, trouble concentrating, anxiety, blurred vision, sweating, irritability, rapid heart rate, inability to think clearly, tingling in extremities, dizziness, hunger, nausea, fatigue, weakness, headache Part 4 Nutrition Therapy Causes Excess food and/or CHO; large meals or excess snacking Physical inactivity Lack of blood glucose monitoring Inadequate diabetes medication Inappropriate timing of medications Overtreatment of hypoglycemia Adverse effect of non-diabetes medications Illness Variability in insulin absorption Variability in rates of digestion/absorption of food Stress Overnight release of hormones Insufficient insulin in P.M. Excessive food at bedtime Lack of blood glucose self-monitoring Severe illness or infection Insulin omitted Increased insulin needs with growth spurts Dehydration Excessive fluid losses Prolonged hyperglycemia Excess medication or inappropriate timing of medications Overcorrection of hyperglycemia with insulin Too little food and/or CHO Missed or delayed meal Increased activity Side effects from non-diabetes medication Treatment Modification of dietary intake and/or adjustment of medication Begin planned physical activity Regular self-monitoring of blood glucose with appropriate education to apply data Add, adjust, or change medication(s) Coordinate timing of medication(s) and food Education for treatment of hypoglycemia Education for drug-nutrient interactions Education for illness management Proper site rotation Address issues of gastroparesis (delayed stomach emptying) Psychosocial assessment for depression, diabetes- related distress, anxiety, eating disorders, and cognitive impairment—referral to mental health specialist Adjust insulin dosages Adjustment of bedtime snack Regular self-monitoring; test for ketones if glucose .250 mg/dL Closely monitor effects of illness on blood glucose; increase frequency of glucose measurement; treat illness if indicated; take DM medications even when eating less; maintain hydration; plan for sick-day management Investigate reasons for omission Frequent blood glucose monitoring Monitor fluid intake; establish plan to take fluids regularly Monitor fluid status; address causal factors, replace fluids Monitor blood glucose regularly; treat mild hyperglycemia Adjust amount and/or type of medication; coordinate timing of medications with food and activity Use appropriate amount of insulin for correction Consume appropriate amount of food and/or CHO Eat meals on time or eat snack if meal will be late Follow guidelines for adjustment of medications or food intake Education for drug-nutrient interactions Complication Risk Factors Treatment Autonomic neuropathy • Cardiovascular (postural hypotension and "silent" heart disease) • Genitourinary (sexual dysfunction, bladder emptying problems) • Gastroparesis (delayed emptying of stomach) Long-standing DM • Optimized glycemic control • For gastroparesis: Therapeutic lifestyle and nutritional changes (small, frequent meals; reduce fat and fiber intakes; use foods with soft consistency; exercise after meals; adjust insulin doses and timing) • Pharmacologic options (cholinergic drugs, dopamine antagonists, motilin-receptor agonists) • Surgical treatment

table on 488

Examples of Algorithms Used to Determine Insulin Dose Diabetes Type T1DM or T2DM T1DM with trace to small amounts of ketones or T2DM with BMI #27 T1DM with moderate to large amounts of ketones or T2DM with BMI .27 T2DM with oral hypoglycemic medications Daily Insulin Dose (Dependent on age, body size, insulin sensitivity, hepatic function, and clinical MD decision) Total daily insulin requirement: weight (lbs) 4 4 OR 0.55 3 weight (kg) Dosage divided: 50% basal; 50% rapid with meals 0.2-0.5 units/kg 0.5-0.7 units/kg body weight for basal insulin Rapid-acting mealtime insulin: based on insulin-to-CHO ratio 0.1-0.3 units/kg body weight for basal insulin Rapid-acting mealtime insulin: based on insulin-to-CHO ratio For example, JP is a 52-year-old gentleman on T2DM medica- tions for the past 10 years. His A1c continues to be out of the acceptable range on his current oral medications. Insulin therapy can be initiated using a long-acting basal insulin (e.g., Lantus) at a dosage of 0.2 units/kg of body weight. If JP weighs 185 lbs, he could start at 17 units of Lantus given once daily. The next step would be to begin rapid-acting insulin based on an insulin-to-carbohydrate ratio for each meal and snack. Sources: Nolte Kennedy MS. Pancreatic hormones and antidiabetic drugs. In Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clini- cal Pharmacology. 12th ed. New York: McGraw-Hill; 2012. http:// accessmedicine.mhmedical.com/content.aspx?bookid5388&Section id545764265. Accessed February 14, 2014. Rystrom JK. Insulin therapy. In Ross TA, Boucher JL, O'Connell BS, eds. American Dietetic Association Guide to Diabetes: Medical Nutrition Therapy and Education. Chicago: American Dietetic Association; 2005: 150-163. Nelms, MN, Long S. Medical Nutrition Therapy: A Case Study Approach. 4th ed. Belmont, CA: Cengage Learning; 2013. Insulin Delivery Regimens Continuous subcutaneous insulin infusion (CSII). This method is an external closed-loop pump that provides a 24-hour programmable basal rate of insulin. The rate can be individualized for changes in insulin sensitivity, sleep, and activity. Additional boluses of insulin are given before meals and snacks. Intensive insulin therapy (multiple daily injections [MDIs]). Basal insulin or background insulin is provided with one to two injections of long-acting insulin such as Lantus. Rapid- or short-acting insulin is given prior to meals and snacks. Allows more flexibility in type and timing of meals. Amount of rapid- or short-acting insulin can be adjusted based on meal composition and/or its carbohydrate content. Conventional therapies ("split" or "mixed" dose). There are two basic conventional therapy regimens. Option #1: Short- or rapid-acting insulin mixed with intermediate-acting insulin1 given before breakfast and before evening meal. Option #2: Combination of short- and intermediate-acting insulin before breakfast, short-acting insulin before evening meals, and intermediate-acting insulin at bedtime.

table on 491

Class Generic Trade Name Action to Hypoglycemia Disadvantages Advantages Susceptibility α-Glucosidase inhibitors (AGIs) Amylin analogs (injectable medication) Biguanides Incretin mimetics (injectable medication) Meglitinides— insulin secretagogues SGLT2 inhibitors Sulfonylurea agents: Second generation Thiazolidinediones Acarbose Miglitol Pramlintide acetate Metformin Exenatide Repaglinide Nateglinide Dapagliflozin Canagliflozin Glipizide Glipizide-GITS Glyburide Glimepiride Pioglitazone Rosiglitazone Precose Glyset Symlin Glucophage Byetta Prandin Starlix Farxiga Invokana Glucotrol Glucotrol XL DiaBeta, Micronase, Glynase PresTab Amaryl Actos Avandia Competitive inhibitor of α-glucosidases— delays intestinal absorption of glucose Delays gastric emptying, suppresses post- prandial glucagon release, suppresses appetite Decreases hepatic glucose production, increases insulin uptake in muscles Mimics glucose- dependent insulin secretion, suppresses elevated glucagon secretion, delays gastric emptying Stimulates insulin secretion in presence of glucose; short- acting Reduces renal glucose reabsorption; increases urinary glucose excretion Stimulates insulin secretion Decreases insulin resistance No Increases risk of insulin-induced hypoglycemia (can be used to treat T1DM or T2DM treated with insulin) No Can cause hypoglycemia when used with sulfonylureas Yes Yes, when taken with insulin and insulin secretagogues Yes No Flatulence, diarrhea, less efficacy, frequent dosing; contraindicated in individuals with intestinal diseases; must take with meals three times/day GI complaints; must be used in syringe separate from insulin; hypersensitivity to pramlintide Transient diarrhea, nausea, bloating, anorexia, flatulence, lactic acidosis (rare); contraindicated in individuals with renal insufficiency or liver or heart failure May decrease absorption of orally administered drugs (drugs requiring rapid absorption such as oral contraceptives, antibiotics) Hypoglycemia, frequent dosing; expensive Hypotension; increased LDL, urinary tract infections Hypoglycemia (more with glyburide); contraindicated in individuals with renal insufficiency; weight gain Weight gain, edema; slow onset; contraindicated in individuals with heart failure Safety, postprandial effect Improves long-term control (A1c) compared to insulin alone; lowers insulin use and body weight Weight control, no hypoglycemia with monotherapy, may be cardiovascular benefits Better glycemic control 1 hour after ingestion/ 4-7 hrs duration; short action with less hypoglycemia at night or with missed meal; glucose- dependent effect on insulin; post-prandial effect Weight loss Inexpensive, long history of effectiveness, only needed once daily for most patients Very effective in insulin- resistant individuals; okay with renal insufficiency; potentially, reduced triglyceride levels Classification Mechanism Brand Names Possible Food-Drug Interactions Sources: Pronsky ZM. Food Medication Interactions. 17th ed. Birchrunville, PA: Food-Medication Interactions; 2012. Ahmann AJ, Riddle MC. Current oral agents for type 2 diabetes; many options, but which to choose when? Postgrad Med. 2002; 111: 32. Beebe CA. Nutrition therapy of type 2 diabetes. In Franz MJ, Bantle JP, eds. American Diabetes Association Guide to Medical Nutrition Therapy for Diabetes. Alexandria, VA: American Diabetes Association; 1999. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA. 2002; 287(3): 360-72. Luna B, Feinglos MN. Oral agents in the management of type 2 diabetes mellitus. American Family Physician. 2001; 63(9): 1747-56. Insulin Replaces endogenous insulin. See Table 17.6 Increased weight; use alcohol with caution. α-Glucosidase inhibitors (AGIs) Delays intestinal absorption of glucose. Precose, Glyset Take with first bite of meal; limit alcohol. Amylin analogs Delays gastric emptying, decreases post-prandial glucagon release, suppresses appetite. Symlin Caution with alcohol. Biguanides Decreases hepatic glucose production, increases insulin uptake in muscles. Glucophage Decreases folate and vitamin B12 absorption; avoid alcohol; take with meals to decrease GI distress. Incretin mimetics Mimics glucose-dependent insulin secretion, suppresses elevated glucagon secretion, delays gastric emptying. Byetta Caution with alcohol; may cause GI disturbances. Meglitinides Stimulates insulin secretion in presence of glucose. Prandin, Starlix Limit alcohol. Sulfonylurea agents (first generation) Stimulates insulin secretion. Dymelor, Diabinese, Tolinase, Orinase Avoid alcohol. Sulfonylurea agents (second generation) Stimulates insulin secretion. Glucotrol, Glucotrol XL, DiaBeta, Micronase, Glynase PresTab Avoid alcohol. Thiazolidinediones Decreases insulin resistance. Actos, Avandia None.

table on 494

Type 2 Diabetes Mellitus in Older Adults Colette LaSalle, PhD, RD San Jose State University Type 2 diabetes mellitus (T2DM) becomes increasingly common with age. Current estimates using standard criteria indicate that approximately one in five people over the age of 65 have elevated fasting blood glucose and/or elevated glycosylated hemoglobin A1c(HbA1c).1,2 However, this estimate does not include people with impaired glucose metabolism with insulin resistance and resultant post-prandial hyperglycemia.2 There are limited data concerning specific blood glucose criteria for the geriatric population, but in 2012 the American Diabetes Association (ADA) released a report, "Consensus Develop- ment Conference on Diabetes and Development," concerning people over the age of 65.3 This report recommends setting glycated hemoglobin (HbA1c) and blood glucose goals at levels similar to those for younger adults for those over age 65 who are healthy and do not have cognitive impairment. However, the older adults represent a very heterogeneous group in terms of functional ability, cognitive status, and years since disease onset, so it is important to individualize goals and interven- tions. For older adults who are not healthy or have some level of cognitive impairment, these goals should be relaxed with a focus on reducing or eliminating signs and symptoms associ- ated with hypo- and hyperglycemia rather than maintaining tight glucose control. Therefore, the desired HbA1c varies based on functional status. For example, the International Diabetes Foundation's (IDF) Global Guideline4 recommends the follow- ing A1c goals: While a carbohydrate-controlled diet can improve blood glucose control, dietary restrictions should also be relaxed in frail, cognitively impaired, very old, and institutionalized individuals because limiting carbohydrates does not improve outcomes and can reduce oral intake.2,5 In fact, frail older adults are more at risk for negative effects of hypoglycemia than from hyperglycemia, which can be addressed with insulin therapy. Therefore, dietitians working with this popu- lation must provide individualized nutrition interventions to minimize signs and symptoms while optimizing oral intake. References 1. Sinclair A, Morley JE, Rodriguez-Mañas L, et al. Diabetes mellitus in older people: position statement on behalf of the International Association of Gerontology and Geriatrics (IAGG), the European Dia- betes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes. J Am Med Dir Assoc. 2012; 13(6): 497-502. 2. Bernstein M, Munoz N; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: food and nutrition for older adults: promoting health and wellness. J Acad Nutr Diet. 2012; 112(8): 1255-77. 3. American Diabetes Association. Standards of Medical Care in Diabetes—2014. Diabetes Care. 2014; 37(Suppl 1): S14-80. 4. International Diabetes Federation. Managing older people with type 2 diabetes global guideline. Brussels, Belgium: International Diabetes Federation; 2013. Available from: http://www.idf.org/sites/ default/files/IDF%20Guideline%20for%20Older%20People.pdf. 5. Dorner B, Friedrich EK, Posthauer ME; American Dietetic Association. Position of the American Dietetic Association: individualized nutrition approaches for older adults in health care communities. J Am Diet Assoc. 2010; 110(10): 1549-53.

table on 497

Prediabetes (Increased Risk for Diabetes) The diagnosis of prediabetes is made for individuals who present with impaired fasting glucose or impaired glucose tolerance (see Box 17.2). These individuals are at high risk for development of diabetes. Early and aggressive intervention with nutrition and lifestyle changes can be crucial to prevent the further development of this disease. Nutrition therapy focused on weight loss where needed is an important first step. Further dietary modifications should include Therapeutic Lifestyle Changes; see Chapter 13 for these guidelines (Box 13.9) and further information on reducing cardiac risk and dyslipidemia with nutrition therapy.

Diagnostic criteria for diabetes are outlined in Box 17.2. There are four ways to diagnose diabetes. Diagnosis can be made on the basis of a fasting plasma glucose of $126 mg/dL ($7.0 mmol/L) or a casual plasma glucose $200 mg/dL ($11.1 mmol/L) with the presence of classic symptoms (unexplained weigh loss, polydipsia, polyuria). Other tests and laboratory measurements used in DM diagnosis and risk assessment are described below. Table 17.5 describes the components of a comprehensive diabetes evaluation as recommended in the 2014 Standards of Medical Care

tongue; thickened ribs [creating barrel chest]; coarsening of body hair as skin thickens and/or darkens); headaches; exces- sive sweating and oily skin; vision disturbances; sleep apnea (and snoring); joint pain; degenerative arthritis; enlarged heart; fatigue; irregular menstrual cycle and/or breast milk production in women; and impotence in men. Untreated, it can lead to severe illness and death. Treatment is dependent upon the cause of the disease. Ninety percent of acromegaly cases are caused by benign tumors; therefore, treatment may include surgery to remove the tumor, radiation, and injection of a GH-blocking drug. Untreated acromegaly can lead to diabetes mellitus and hypertension. It also increases risk for cardiovascular disease and colon polyps that may lead to cancer. Cushing's Syndrome Cushing's syndrome, also called hypercortisolism, is a rare disorder caused by chronic exposure to excessive circulating cortisol. The most common causes of Cushing's syndrome are Cushing's disease (an adrenocortico- tropic hormone-secreting tumor) or use of synthetic steroids to treat other conditions. Overproduction of adrenocorticotropic hormone (ACTH) in Cushing's disease stimulates the adrenal glands to overproduce the steroid hormone cortisol. Cushing's syndrome is found more often in women than in men and affects all age groups, but peak incidence is seen in middle age. Common symptoms of Cushing's syndrome (see Figure 17.17) include upper body obesity, moon face, redness of the face, severe fatigue and muscle weakness, infertility, hypertension, backache, hyperglycemia, easy bruising, bluish-red striae on skin, and development of diabetes mellitus. Women may expe- rience increased growth of facial hair and hirsutism (excessive body and facial hair), oligomenorrhea, or amenorrhea; males may experience impotence. Patients may also present with neurological symptoms, including memory difficulties and neuromuscular disorders. Cushing's progresses slowly and gradually in most cases, and can therefore go unrecognized for some time. Treatment of Cushing's syndrome is dependent on the cause of the excess cortisol. If the cause is long-term use of synthetic steroid medications, dosage may be reduced until symptoms are controlled. Surgery or radiation may be used Source: Wellcome Image Library/Custom Medical Stock Photo—All rights reserved. to treat pituitary tumors. Surgery, radiation, chemotherapy, immunotherapy, or a combination may be used to treat ecto- pic ACTH syndrome. Prognosis is also dependent upon cause of the disease. Most cases can be cured, although recovery may be complicated by various aspects of the causative illness. Hypopituitarism Pituitary tumors are the most common cause of hypopituitarism, which results in deficiencies of GH, gonadotropin, ACTH, and thyrotropin (TSH). Manifestations of these disorders are shown in Table 17.20. Diabetes Insipidus Diabetes insipidus (DI), not to be con- fused with diabetes mellitus, results from insufficient produc- tion of vasopressin by the hypothalamus (the portion of the brain that stimulates the pituitary gland). Vasopressin is produced by the hypothalamus, but stored and released into the blood- stream by the pituitary gland. Normally, vasopressin controls the kidneys' output of urine. DI causes polyuria (.3 L/24 hr) and polydipsia, resulting from excessive loss of fluid. Treatment of DI depends on its cause. Treatment of the cause usually resolves DI. Common causes of DI include the following: • Malfunctioning hypothalamus • Malfunctioning pituitary gland • Brain injury • Tumor • Tuberculosis • Blockage of cerebral arteries • Encephalitis • Meningitis • Sarcoidosis Adrenal Cortex Disorders A number of common deficiencies result from either insuf- ficient or excess secretion of adrenal cortex hormones. And, as with other endocrine disorders, symptoms are the result of either the absence or magnification of effects of the hormones involved.

Excess Secretion of Glucocorticoids Prolonged expo- sure to high levels of endogenous or exogenous glucocorti- coids results in the condition Cushing's syndrome. Insufficient Secretion of Adrenal Cortex Steroids Both adrenal glands must be nonfunctional (or removed) before adrenocortical insufficiency can occur.2 As a result of either occurrence, both glucocorticoid (cortisol) and mineral corti- coid (aldosterone) hormone production is lacking. Death may result from untreated adrenocortical insufficiency. Primary adrenal insufficiency is uncommon, but iatro- genic (caused by medical treatment) adrenal insufficiency is more frequent, although exact incidence is unknown. Auto- immune Addison's disease is the more common form of adre- nal insufficiency. Addison's afflicts men and women and can occur at any age, but is most common in people 30-50 years of age. Adrenal insufficiency can be classified as either primary or secondary. Primary adrenal insufficiency (Addison's dis- ease) is caused by a dysfunctional adrenal cortex that impairs both glucocorticoid and mineral corticoid production. Sec- ondary adrenal insufficiency results from inadequate ACTH production by the anterior pituitary, resulting primarily in deficient glucocorticoid secretion. Adrenal insufficiency can further be classified as congenital or acquired. Primary adrenal insufficiency results from destruction of the adrenal cortex. Aldosterone is produced by the medulla of the adrenal gland; cortisol is produced in the adrenal cor- tex. Clinical findings manifest after 90% of the adrenal cortex has been destroyed. Potential causes of this destruction are as follows: • Autoimmune • Infectious (e.g., mycobacterial, fungal) • Neoplastic (e.g., primary, metastatic) • Traumatic • Iatrogenic (e.g., surgery, medication) • Vascular (e.g., hemorrhage, emboli, thrombosis) • Metabolic (e.g., amyloidosis) With destruction of the adrenal cortex, feedback inhibition of the hypothalamus and anterior pituitary gland 516 Part 4 Nutrition Therapy is interrupted. Symptoms associated with aldosterone defi- ciency in Addison's disease progress slowly and insidiously. Typical symptoms of Addison's disease reflect loss of gluco- corticoid and mineral corticoid action. Since aldosterone is essential for life, the condition can be fatal. Aldosterone defi- ciency causes reduced potassium loss in the urine, resulting in hyperkalemia, which in turn results in disturbed cardiac rhythm. Hyponatremia caused by excessive urinary loss of sodium results in hypotension. Cortisol deficiency results in poor response to stress, hypoglycemia (resulting from reduced gluconeogenesis), and hyperpigmentation (from excessive secretion of ACTH).2 Addison's disease may coexist with other autoimmune dis- orders, especially thyroid disease, premature ovarian failure, and T1DM. Treatment of Addison's disease involves replacing or substituting hormones not being produced by the adrenal gland. Patients with Addison's disease should not restrict salt in their diets. Patients with concurrent primary hypertension may restrict salt intake rather than discontinue mineral cor- ticoid replacement. Patients living in warm climates should increase salt intake due to increased loss of salt through perspiration.

A1c (Glycosylated Hemoglobin) Glycosylated hemo- globin assays (hemoglobin A1c or A1c) measure the amount of glucose bound to hemoglobin protein. The higher the glucose concentration in the blood, the more hemoglobin is glycated (via addition of a glucose molecule to amino acid side-chains), thus making it a valid test to measure degree of hyperglycemia. Because red blood cells have a life span of 120 days, A1c can measure the average glucose concentration for the previous 2-3 months. This test his- torically has been used to monitor adequacy of glucose control after diagnosis. Now with standardization of the test, an A1c of $6.5% is being used as an additional option for diagnosis.7 Oral Glucose Tolerance Test Oral glucose tolerance tests (OGTTs) are rarely needed to diagnose T1DM due to the sudden onset of symptoms accompanied by hyper- glycemia. In fact, OGTT is contraindicated in infants and young children, but it is the standard screening for gesta- tional diabetes. The one-step OGTT is administered after at least 3 days of an unrestricted diet providing at least 150 grams of carbohydrate (CHO) daily and normal physi- cal activity. The test is preceded by an overnight fast of 8-14 hours, during which water may be drunk. Smoking is not permitted during the test. After collection of a fast- ing blood glucose sample, a drink containing 75 grams of anhydrous glucose in 250-300 mL of water is consumed over a 5-minute period. Timing of the test begins at the beginning of the drink. Blood samples are collected at the 1- and 2-hour mark after the test load. In a person with- out diabetes, blood glucose levels rise, then fall quickly to normal. In individuals with diabetes, blood glucose levels rise higher than normal, then fall slowly back to normal. A 2-hour plasma glucose of $200 mg/dL ($11.1 mmol/L) is diagnostic for DM (see Box 17.2). Islet Cell Autoantibodies Autoantibody testing is not compulsory to diagnose T1DM, but it can be valuable in screening individuals at high risk for developing diabetes. In daily clinical practice, diabetes-related autoantibody testing is largely performed to differentiate between autoimmune T1DM and T2DM. Islet cell autoantibodies serve as indi- cators of the body's destructive immune response against its own b cells. Diabetes-related autoantibodies that may be measured include islet cell cytoplasmic autoantibodies (ICA), insulin autoantibodies (IAA), glutamic acid decar- boxylase autoantibodies (GADA), GAD65 autoantibodies, insulinoma-associated-2 autoantibodies (IA-2A), ICA512 autoantibodies, and protein tyrosine phosphatase-like autoantibodies.3,14 Glutamic Acid Decarboxylase Autoantibodies Tests for glutamic acid decarboxylase autoantibodies (GADA) mea- sure specific islet cell antigens. GADA have been found in 70%-90% of individuals with T1DM, and have been shown to be the most sensitive marker for identifying persons at risk for developing T1DM. They are generally more preva- lent in older children and individuals diagnosed with T1DM at a later age

Islet Cell Autoantibodies The islet cell autoantibodies (ICA) test measures a group of islet cell autoantibodies. ICA have been found in 70%-80% of individuals younger than 30 years of age with newly diagnosed diabetes. Among individuals with T1DM, prevalence of ICA decreases the longer an individual has diabetes. Existence of ICA in relatives without diabetes has been shown to be a sign of increased risk for the disease. Individuals without diabetes who test positive for one or more islet autoantibodies are at increased risk for T1DM, but since there are currently no prevention strategies for T1DM, test- ing in this population is primarily used in conjunction with research protocols.3 Insulin Autoantibodies The presence of insulin autoantibod- ies (IAA) is evidence of ongoing destruction of b cells. IAA testing must be performed before insulin therapy is initiated since the test does not determine whether the body's im- mune system is making autoantibodies against endogenous or exogenous insulin.14 IAA are found primarily, though not exclusively, in young children developing T1DM as an early predictive marker. They are rarely established in adults with T1DM.14 C-Peptide As discussed earlier in this chapter, insulin is secreted as two polypeptide chains joined by disulfide bonds. C-peptide is released when the two chains separate. C-peptide levels then can be used to measure the insulin production in the body. Autoantibodies, as previously outlined, are not always useful in determining the overall beta cell function of the pancreas. C-peptide levels allow the determination of insulin production in both T1 and T2DM. Medical Treatment of Diabetes Mellitus To survive, individuals with T1DM must depend on daily administration of exogenous insulin in conjunction with nutrition therapy and physical activity to mimic the insulin secretion in an individual without diabetes.7 Treatment of T2DM utilizes a variety of medications (including insulin), nutrition therapy, and lifestyle changes. The first step in treat- ment for T2DM is weight loss and increased physical activity. The next step of treatment includes the initiation of pharma- cological agents, which are discussed below. Treatment goals for both T1 and T2DM include avoiding hyperglycemia and retarding development of complications within an acceptable level of treatment side effects. The closer to the normal range blood glucose can be maintained over the long term, the lower the risk of complications.3,7,15,16 Box 17.5 describes risk factors and treatments for short- and long-term complications of diabetes. Medical care of diabetes mellitus should be the coordi- nated effort of an interdisciplinary team with expertise and a special interest in diabetes. The team should be comprised of (but not limited to) the individual with diabetes and the fol- lowing care providers:17 • Physicians • Registered dietitian nutritionists (RD/RDN) or dietetic technicians, registered (DTR)

Glucose Note: 1All glucose is transported across plasma membranes by passive facilitated diffusion, except in the small intestine, where it is transported by active transport. Source: Sherwood L. Human Physiology: From Cells to Systems. 8th ed. Belmont, CA: Cengage; 2013. Transporter (GLUT)1 Substrate Tissue Distribution Function GLUT-1 Glucose Most cells Transports glucose across blood-brain barrier GLUT-2 Glucose, galactose, fructose Liver, b cells of pancreas, hypothalamus, basolateral membrane of small intestine, kidney tubules Transports glucose from kidney and intestinal cells into adjacent bloodstream by means of co-transport carriers GLUT-3 Glucose Brain (neurons), kidney, placenta, testes Transports glucose into neurons GLUT-4 Glucose Skeletal and cardiac muscle, white and brown adipose tissue Transports the majority of glucose used by most cells of the body via the influence of insulin GLUT-5 Fructose Mucosal surface of small intestine, adipose tissue, skeletal muscle, sperm Fructose transport

Table on 479

Hyperglycemic Hyperosmolar Syndrome and Diabetic Ketoacidosis Hyperglycemic Hyperosmolar Syndrome (HHS) Diabetic Ketoacidosis (DKA) Source: Powers AC. Chapter 344. Diabetes mellitus. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18e. New York: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid5331&Sectionid540727149. Accessed February 7, 2014. 506 Part 4 Nutrition Therapy Copyright 2016 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it. Characteristics • Adequate insulin to prevent lipolysis and ketogenesis but inadequate to maintain normoglycemia • Occurs most often in T2DM • Typically occurs in those .55 years old • Frequently occurs in residents of long-term care facilities • Hyperglycemia • Metabolic acidosis • Ketogenesis • Occurs most often in T1DM and those with new-onset T2DM who are obese and have impaired insulin secretion and insulin action Causes • Dehydration from inadequate fluid intake or excess fluid losses • Prolonged hyperglycemia • Infections • Acute illnesses (cerebrovascular accident, alcohol/drug abuse, pancreatitis, pulmonary embolism, myocardial infarction, trauma) • Inadequate insulin • Pump malfunction • Drug abuse • Pregnancy Symptoms • Progresses slowly (over days and weeks) • Polyuria • Polydipsia • Progressive decline in level of consciousness • Fever (due to underlying infection) • Volume depletion • Polyuria • Polydipsia • Vomiting • Abdominal pain • Dehydration (loss of skin turgor, dry mucous membranes, tachycardia, hypotension) • Acetone breath • Kussmaul respirations • Lethargy, cerebral edema; may lead to coma Laboratory findings: Plasma glucose Arterial pH Serum bicarbonate Urine ketones Serum ketones Serum osmolality .250-600 mg/dL .7.3 Normal to slightly ↓ Small Small .330-380 mOsm/kg 600-1200 mg/dL 6.8 to 7.3 ,15 mEq/L Positive Positive 300-320 mOsm/kg Treatment • Hospitalization for slow rehydration • Treatment for underlying medical problems • Insulin may or may not be required • Hospitalization for administration of IV fluids • Insulin • Control of serum electrolytes Prevention • Routine hydration • Adequate monitoring Identify cause(s) to determine approach to prevention. Can include: • Regular self-monitoring • Test for ketones if BG .250 mg/dL • Monitor effects of illness on BG closely • Take medications even when eating less • Sick-day management plan • Probe rationale for omitting insulin

Table on 506

• Bradycardia • Slow reflexes and movement • Slow mental responsiveness (diminished alertness, slow speech, poor memory) • Pitting edema of lower extremities • Periorbital puffiness • Myxedema • Goiter (see Figure 17.14) • Loss of scalp hair, axillary hair, pubic hair, or a combination • Abdominal distension Medical Treatment Treatment of hypothyroidism consists of administration of exogenous thyroid hormone to supple- ment or replace endogenous thyroid hormone production, with one exception. If hypothyroidism is caused by iodine deficiency, it can be remedied through adequate intake of dietary iodine.35 Clinical benefits of either treatment begin in 3-5 days and level off after 4-6 weeks. Patients should be monitored for signs and symptoms of overtreatment (tachycardia, pal- pitations, nervousness, tiredness, headache, increased excit- ability, sleeplessness, tremors, possible angina).35 Nutrition Therapy for Hypothyroidism No special nutrition therapy is required for patients with hypothyroidism other than correcting iodine deficiency where it exists. However, there are nutrition implications for patients receiving hypothyroidism medications. For example, iron, calcium, and magnesium supplements should be t®aken atleast4hoursbeforeorafterlevothyroxine(Synthroid ). Hyperthyroidism Definition Hyperthyroidism or thyrotoxicosis is character- ized by excessive secretion of thyroid hormones.2,35 Table 17.19 Common Causes of Hyperthyroidism Graves' disease Autoimmune thyroid disease distinguished by Sources: Fitzgerald PA. Endocrine disorders. In Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis and Treatment 2014. New York: McGraw-Hill; 2014. http://accessmedicine.mhmedical.com/content .aspx?bookid5330&Sectionid544291028. Accessed February 15, 2014. Epidemiology and Etiology The most common cause of hyperthyroidism is Graves' disease (see Table 17.19), which accounts for approximately 60%-80% of cases.36 Graves' dis- ease is an autoimmune disease resulting in excessive produc- tion of thyroid hormones. Pathophysiology Graves' disease is an organ-specific autoimmune disease in which an antibody (thyroid- stimulating immunoglobulin [TSI]) mistakenly targets TSH receptors on the thyroid cells. This antibody stimulates both secretion and growth of the thyroid in a manner similar to TSH, but it is not subject to negative-feedback inhibition by thyroid hormone.2,36 Clinical Manifestations The hypermetabolic effects of hyperthyroidism affect every organ in the body. Key symp- toms include palpitation, nervousness, sweating, hyperdef- ecation, heat intolerance, and oligomenorrhea. General signs of hyperthyroidism include weight loss despite increased appetite, drooping eyelids and stare, sinus tachycardia, atrial fibrillation, tremor, and muscle weakness. A well-known char- acteristic of Graves' disease, but not other types of hyperthy- roidism, is exophthalmos (bulging eyes) (see Figure 17.15). Medical Treatment Three general methods of treatment are used to suppress excess thyroid hormone secretion:2,36 • Surgical removal of the oversecreting portion of the thyroid gland • Administration of radioactive iodine to selectively destroy thyroid glandular tissue • Antithyroid drugs that specifically interfere with thyroid hormone synthesis

Thyroidectomy is the oldest manner of treatment for hyper- thyroidism. Nevertheless, because hyperthyroidism can usually be successfully treated with antithyroid medications and radio- active iodine, thyroidectomy is reserved for cases where these treatments fail. Antithyroid drugs (e.g., methimazole, propyl- thiouracil) have been used since their introduction in the 1940s. These drugs inhibit synthesis of T4 and T3, leading to a gradual decline in thyroid hormone levels over a period of 2-8 weeks. Radioactive iodine therapy is the most widespread treatment of hyperthyroidism in the United States. Administered orally as a single dose (capsule or liquid), radioactive iodine acts less rap- idly than antithyroid medications or thyroidectomy, but it is suc- cessful and reliable, and does not necessitate hospitalization.36 Table 17.20 Hyperpituitarism and Hypopituitarism Disorder Symptoms Source: © Cengage Learning. 514 Part 4 Nutrition Therapy Nutrition Therapy for Hyperthyroidism While no special diet must be followed by individuals with hyperthyroidism, they should be monitored for drug-nutrient interactions related to any medications they receive. Pituitary Disorders Pituitary disorders are a result of hypersecretion or hyposecre- tion. The most common disorders include pituitary tumors, acromegaly, Cushing's disease, and diabetes insipidus. Pituitary Tumors Pituitary tumors are adenomas found in the pituitary gland. They are slow growing and most are benign. Autopsy data from the National Institute of Diabetes and Digestive and Kidney Diseases indicates that 25% of the U.S. population has some form of small pituitary tumor. Pitu- itary tumors often present with signs and symptoms related to hypofunction or hyperfunction. Tumors that produce hor- mones are called functioning tumors, whereas those that do not produce hormones are called nonfunctioning tumors. Hyperpituitarism Increased secretion of pituitary hor- mones can result in prolactinoma, acromegaly, Cushing's disease, and thyroid-stimulating hormone-secreting tumor. Prolactinoma and thyroid-stimulating hormone-secreting tumor are summarized in Table 17.20. Acromegaly Acromegaly is a Greek word that means "extremities enlargement." It results from growth hormone (GH) hypersecretion, which causes excessive growth (see Figure 17.16). Affecting mostly middle-age (35- to 50-year-old) adults, elevated GH levels are associated with changes in appearance (coarsening of facial features as bones grow; enlarged hands and feet; protruding jaw; enlarged lip, nose,

Normal Anatomy and Physiology of the Endocrine System Many functional interactions take place among the various ductless glands (see Figure 17.1) that make up the endocrine system. This chapter focuses only on endocrine glands and disorders related to nutrition and nutritional status. Classification of Hormones Hormones released from endocrine glands regulate activities throughout the body. In a healthy state, hormones are released when their actions are required and inhibited when effects are achieved. Endocrine diseases manifest through either hyperfunction (exceptionally high blood concentrations of a hormone), hypofunction (depressed levels of hormones in the blood), or abnormal target-cell responsiveness.1,2 The functions of hormones may be grouped into four categories:3 • • • Homeostasis • Regulation of metabolism and nutrient supply There are three chemical classes of hormones: (1) peptides and proteins, (2) amines, and (3) steroids.1 The majority of hormones fall into the category of peptides and proteins, which are amino acid derivatives. Peptide hormones are secreted by the following glands: hypothalamus, anterior and posterior pituitary glands, pineal gland, pancreas, para- thyroid gland, gastrointestinal tract, kidney, liver, thyroid C cells, heart, and thymus. Amines are derivatives of the amino acid tyrosine. They are secreted by the thyroid gland and adrenal medulla. Steroid hormones, derived from cho- lesterol, are secreted by the adrenal cortex, gonads, and placenta.1 Endocrine Function Pituitary Gland The pituitary gland is located in the bony cavity at the base of the brain just below the hypothalamus (see Figure 17.2). It is connected to the hypothalamus by a thin connecting stalk called the pituitary stalk. The pituitary gland actually consists of two anatomically and functionally distinct glands: the anterior pituitary and the posterior pituitary. Location is the only thing they have in common. The anterior pituitary secretes six hormones (see Figure 17.3) that control secretion of various other hor- mones. None of the hormones is secreted at a constant rate; rather, secretion is regulated by hypothalamic hormones and feedback from target gland hormones. The posterior pituitary releases vasopressin and oxytocin, hormones synthesized by the hypothalamus. Thyroid Gland The thyroid gland, which is responsible for controlling metabolic rate, lies over the trachea just below the larynx, and consists of two lobes connected by a thin strip called the isthmus (see Figure 17.4). The thyroid hormones are two iodine-containing hor- mones derived from the amino acid tyrosine: thyroxine (T4 or tetraiodothyronine) and triiodothyrone (T3). The pre- fixes tetra- and tri- and subscripts 4 and 3 denote the number of iodine atoms incorporated into each of these hormones. T4 is the major hormone secreted by the thyroid, but T3 is more active. The conversion of T4 to T3 within the anterior

pituitary, liver, and kidney accounts for approximately two- thirds of T3 production. Response from increased secretion of thyroid hormone (which may affect several different organs and processes in the body) takes several hours to become apparent. Maximal response does not become apparent for several days. Because thyroid hormone is not rapidly degraded, the response to increased secretion continues to be expressed over a period of days or even weeks after plasma thyroid hormone concentrations return to normal.2 Adrenal Glands The two adrenal glands are embedded above each kidney (see Figure 17.1) and are encapsulated in fat. Each adrenal gland is composed of two endocrine organs. The inner portion, the adrenal medulla, forms part of the sym- pathetic nervous system and secretes epinephrine, norepi- nephrine, and catecholamines.2 The outer layers, known as the adrenal cortex, compose 80%-90% of the adrenal gland and produce over 50 known adrenocortical hormones. Structural variations in these hor- mones confer different functional capabilities and allow them to perform different primary actions.1,3 Aldosterone directly influences the kidney to retain sodium, and thus has an integral role in regulating fluid bal- ance and blood volume. Cortisol, a glucocorticoid, is secreted in response to physical (trauma, surgery, intense heat or cold), chemical (reduced O2 supply), physiologic (heavy exercise, hemorrhagic shock, pain), psychological or emotional (anxi- ety, fear, sorrow), and social (personal conflict, change in lifestyle) stresses. Cortisol stimulates hepatic gluconeogen- esis; inhibits glucose uptake and use by tissues (except brain); stimulates protein degradation (especially in muscle) for use in gluconeogenesis or protein synthesis; and facilitates lipol- ysis. Administration of glucocorticoids inhibits almost every step of the inflammatory process, making them effective anti- inflammatory drugs. Lastly, cortisol permits catecholamines to induce vasoconstriction. Dehydroepiandrosterone (a male "sex" hormone) produced in the adrenal cortex is identical or similar to that produced by the gonads.2 Endocrine Pancreas The pancreas is located in the abdom- inal cavity adjacent to the upper part of the small intestine (see Figure 17.1). Different groups of cells within the pancreas carry out different functions. Cells making up the exocrine pancreas are responsible for secretion of fluid and various digestive enzymes that are secreted via the pancreatic duct into the duodenum (see Chapter 16). The endocrine cells of the pancreas (see Figure 17.5) include the alpha cells, which secrete glucagon and GLP-1 (glucagon-like-peptide); beta cells, which secrete insulin; delta cells, which secrete somatostatin; and the F cells, which secrete pancreatic polypeptide. These cells make up an anatomically small por- tion of the pancreas, but the hormones they secrete play a vital role in energy regulation and fuel homeostasis. Endocrine Control of Energy Metabolism Energy use in the body is constant, but ingestion of energy- yielding nutrients is sporadic. This means that excess energy taken in meals must be stored for later use between meals. About 1500 kcalories (less than a day's worth of energy) are stored as carbohydrate in the form of glucose (circulating in blood) and as glycogen (liver and muscle cells). Carbohydrate is the body's primary energy source and the preferred source of energy for brain cells. Excess carbohydrate (beyond what is used for glucose and glycogen) is converted to and stored as fat (triglycerides). Fat, the body's primary energy reser- voir, can provide about 2 months' worth of energy during a prolonged fasting period. Fat is stored in adipose tissue in the form of triglycerides, and also circulates in the blood as free fatty acids. Protein is not stored as an energy source in the same manner as carbohydrate and fat, but can be used for energy as a "last resort." Protein can be converted to glu- cose (gluconeogenesis) to provide energy for the brain dur- ing a prolonged fast. Following meals, ingested nutrients are absorbed and enter the bloodstream; this period is termed the fed state, and its major metabolic pathways are represented by the blue anabolism arrows in Figure 17.6. During this period of time, glucose functions as the main energy source because most cells have a preference to use glucose. Additional amounts of glucose or fat not immediately used for energy or structural repairs are converted into their storage forms: glycogen or triglycerides, respectively. It takes approximately 4 hours for a typical meal to be absorbed. During the time period when no nutrients are in the gastrointestinal tract (fasting state), endogenous energy stores are mobilized for energy, as indicated by the red catabolism arrows in Figure 17.6. Synthesis of protein and fat is abbreviated, and stored forms of these nutrients are catabolized for glucose formation and energy produc- tion, respectively. Through mechanisms of gluconeogenesis and glucose sparing, the blood glucose level is sustained to nourish the brain. As outlined in Table 17.2, hormones—in particular the pancreatic hormones—afford the means to manage and control fuel homeostasis.4 While cortisol, growth hormone (GH), and epinephrine have effects that influence blood glu- cose concentration, insulin and glucagon (as illustrated in Figure 17.7) are the primary hormones that maintain normal blood glucose concentration (70-110 mg/100 mL). Insulin Insulin is initially secreted as a prohormone, pre- proinsulin. Preproinsulin is processed first to proinsulin and then, with the removal of a peptide sequence (c-peptide) and the subsequent disulfide bonding between two peptide chains (see Figure 17.8), active insulin is produced. Active insulin enters the blood via the portal vein and has an approximate half-life of 5 minutes. It is then degraded back into the two separate chains and becomes inactive.3 Insulin is an anabolic hormone that controls the meta- bolic fate of carbohydrate, protein, and lipid (Table 17.2 sum- marizes its effects). In general, insulin promotes the uptake of glucose into hepatic, muscle, and adipose cells as well as the stimulation of glycogen, triglyceride, and protein synthesis. Insulin secretion is stimulated by an increased level of blood glucose and by the action of counter-regulatory hormones including growth hormone. In order for glucose, fructose, or galactose to be absorbed into the cell, transport molecules—GLUT-1 through -5, listed in Table 17.3—are necessary. GLUT-4 is insulin dependent, as described further below. Most cells, such as the enterocytes in the small intestine, need more than one type of transport molecule. The type of transporter available on the cell reflects the individual cell requirements for fuel. Most tissues in the body depend on insulin for transpor- tation of glucose from the bloodstream into cells to be used for energy. There are exceptions: cells of the brain, and liver, are readily permeable to glucose even in the absence of insu- lin.1,4 The GLUT-4 transporter (which is insulin dependent) is present in skeletal and cardiac muscle and in the adipocytes. Insulin allows the translocation of the GLUT-4 from the inte- rior of the cell to the cell membrane, where it transports glu- cose into the cell (see Figure 17.9). The net effect of insulin is to promote glucose oxidation, glycogen storage, and triglycer- ide storage.3,4 The most pronounced effect of insulin on protein metabolism is seen in skeletal muscle and the liver. It pro- motes active transport of amino acids from the blood into muscle and other tissues, thus promoting protein synthesis within cells. This anabolic effect of insulin on protein metab- olism produces a positive nitrogen balance. When insulin is deficient, there is net loss of protein, or negative nitrogen balance. These effects demonstrate the importance of insulin in tissue growth. Glucagon Glucagon is the hormone released from alpha cells of the pancreas when blood glucose levels fall below the normal range, necessitating a source of energy to maintain homeostasis. Glucagon stimulates the break- down of stored glycogen (glycogenolysis) and the produc- tion of new glucose from amino acids (gluconeogenesis), and thus raises blood glucose. Glucagon also stimulates

• Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) • Eating patterns, physical activity habits, nutritional status, and weight history; growth and development in children and adolescents • Diabetes education history • Review of previous treatment regimens and response to therapy (A1C records) • Current treatment of diabetes, including medications, medication adherence and barriers thereto, meal plan, physical activity patterns, and readiness for behavior change • Results of glucose monitoring and patient's use of data • DKA frequency, severity, and cause • Hypoglycemic episodes ◆ Hypoglycemia awareness ◆ Any severe hypoglycemia: frequency and cause • History of diabetes-related complications ◆ Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of foot lesions; autonomic, including sexual dysfunction and gastroparesis) ◆ Macrovascular: CHD, cerebrovascular disease, and PAD ◆ Other: psychosocial problems,* dental disease* Physical Examination • Height, weight, BMI • Blood pressure determination, including orthostatic measurements when indicated • Fundoscopic examination* • Thyroid palpation • Skin examination (for acanthosis nigricans and insulin injection sites) • Comprehensive foot examination ◆ Inspection ◆ Palpation of dorsalis pedis and posterior tibial pulses ◆ Presence/absence of patellar and Achilles reflexes ◆ Determination of proprioception, vibration, and monofilament sensation Laboratory Evaluation • A1c, if results not available within past 2-3 months • If not performed/available within past year ◆ Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides ◆ Liver function tests ◆ Test for urine albumin excretion with spot urine albumin-to-creatinine ratio ◆ Serum creatinine and calculated GFR ◆ TSH in type 1 diabetes, dyslipidemia, or women over age 50 Referrals • Eye care professional for annual dilated eye exam • Family planning for women of reproductive age • Registered dietitian for MNT • Diabetes self-management education • Dentist for comprehensive periodontal examination • Mental health professional, if needed

table on 486

Insulin Type Brand Name Onset of Action Peak of Action (hours) Duration of Action (hours) Comments Rapid-Acting Insulin Analogs Lispro Aspart Glulisine Short-Acting Regular Intermediate-Acting NPH Humalog Novolog Apidra Humulin R, ReliOn Humulin N, ReliOn 5-15 min 5-15 min 5-15 min 30-60 min 30-90 3-5 30-90 3-5 30-90 3-5 2-4 5-8 Can be used in pump therapy Can be used in pump therapy Can be used in pump therapy Can be mixed with longer- acting insulin Usually given in 2 daily doses Cannot be mixed with other insulin Cannot be mixed with other insulin 70% NPH, 30% regular 75% intermediate, 25% lispro 70% intermediate, 30% aspart Extended Long-Acting Analog 2-4 hrs 4-10 2-4 hrs Peakless 1-3 hrs 6-8 30-60 min Dual 5-15 min Dual 5-15 min Dual 10-18 20-24 18-22 10-16 12-20 12-20 Insulin glargine Insulin detemir Premixed 70/30 75/25 lispro analog mix 70/30 aspart analog mix Lantus Levemir Humulin 70/30, Novolin 70/30 Humalog mix 75/25 Novolog mix 70/30 S

table on 491

Table 17.9 Nutrition Assessment for Diabetes Mellitus Client History • Previous medical conditions or surgeries (personal, patient, family, medical, and social) • Medications: both prescription and over-the- counter (laxatives, fiber supplements) • Socioeconomic status/food security • Support systems • Education—primary language Food-/Nutrition- Related History • Ability to chew; use and fit of dentures • Problems swallowing • Nausea, vomiting • Constipation, diarrhea • Heartburn • Any other symptoms interfering with ability to ingest normal dietFood-/Nutrition- Related History (continued) • Ability to consistently purchase adequate amounts of food on a daily basis • Ability to feed self • Ability to cook and prepare meals • Food allergies, preferences, or intolerances • Previous food restrictions • Ethnic, cultural, and religious influences • Use of alcohol, vitamin, mineral, herbal, or other type of supplements • Previous nutrition education or medical nutrition therapy • Eating pattern: 24-hour recall, diet history, food frequency Anthropometric Measurements • Height • Current weight • Weight history: highest adult weight; usual body weight • Reference weight (BMI) Biochemical Data, Medical Tests and Procedures Visceral Protein Assessment • Albumin • Prealbumin • Transferrrin • Retinol-binding protein • C-reactive protein Hematological Assessment • Hemoglobin • Hematocrit • MCV • MCHC • MCH • TIBC Lipid Assessment • Total cholesterol • HDL • LDL • Triglyceride Renal Assessment • BUN • Creatinine • Creatinine clearance • Spot urinalysis for albumin: creatinine ratio • Glomerular filtration rate (GFR) Endocrine- Specific Biochemical Data, Medical Tests and Procedures • Fasting plasma glucose • Oral glucose tolerance test • Hemoglobin A1c • C peptide • Islet cell autoantibodies, insulin autoantibodies, glutamic acid decarboxylase autoantibodis • Screening for celiac disease: transglutaminase or anti-endomysial antibodies • T3 (triiodothyronine) • T4 (thyroxine) • TSH (thyroid-stimulating hormone) • TRH (thyrotropin-releasing hormone)

table on 495 and 496

Academy of Nutrition and Dietetics evidence-based nutrition practice guidelines recommend the following structure for the implementation of medical nutrition therapy (MNT) for adults with diabetes: • A series of three to four encounters with an RD lasting from 45 to 90 minutes. • The series of encounters should begin at diagnosis of diabetes or at first referral to an RD for MNT for diabetes and should be completed within 3-6 months. • The RD should determine whether additional MNT encounters are needed. • At least one follow-up encounter is recommended annually to reinforce lifestyle changes and to evaluate and monitor outcomes that indicate the need for changes in MNT or medication(s); an RD should determine whether additional MNT encounters are needed.

table on 496

BOX 17.11 CLINICAL APPLICATIONS Estimating Energy Requirements in GDM To calculate a woman's (19 years and older) energy needs during pregnancy, Estimated Energy Requirements (EER) must first be calculated: EER5354 2(6.93A)1PA3(9.363W17263H) Where A 5 age in years; PA 5 physical activity coefficient (1.0 [sedentary], 1.12 [low active], 1.27 [active], 1.45 [very active]); W 5 weight in kg; H 5 height in meters. To estimate energy requirements for pregnant women who are at a normal weight: • 1st trimester 5 Adult EER 1 0 • 2nd trimester 5 Adult EER 1 160 kcal 1 180 kcal • 3rd trimester 5 Adult EER 1 272 kcal Institute of Medicine guidelines for recommended total (cumulative) weight gain during pregnancy are based on prepregnancy BMI. These recommendations are: • Underweight (,18.5 kg/m2): 28-40 pounds • Normal weight (18.5-24.9 kg/m2): 25-35 pounds • Overweight (25.0-29.9 kg/m2): 15-25 pounds • Obese ($30.0 kg/m2): 11-20 pounds. Sources: Academy of Nutrition and Dietetics. Gestatio

table on 509

Nutrient or Food Type Recommendation Meal Planning Tips Sources: Adapted from American Dietetic Association. Gestational Diabetes Mellitus (GDM) Evidence-Based Nutrition Practice Guideline; 2009. Academy of Nutrition and Dietetics. Gestational diabetes. In Nutrition Care Manual. http://www.nutritioncaremanual.org. Accessed February 15, 2013. Energy Intake should be sufficient to promote adequate, but not excessive, weight gain to support fetal development and to avoid ketonuria. Daily minimum of 1700-1800 kcal is an appropriate starting goal. Include 3 small- to moderate-sized meals and 2-4 snacks. Space snacks and meals at least 2 hours apart. A bedtime snack (or even a snack in the middle of the night) is recommended to diminish the number of hours fasting. Carbohydrate A minimum of 175 g CHO daily, allowing for the approximately 33 g needed for fetal brain development. Recommendations are based on effect of intake on blood glucose levels. Intake should be distributed throughout the day. Frequent feedings, smaller portions, with intake sufficient to avoid ketonuria. Common carbohydrate guidelines: 2 carbohydrate choices (15-30 g) at breakfast, 3-4 choices (45-60 g) for lunch and evening meal, and 1-2 choices (15 to 30 g) for snacks. Recommendations should be modified based on individual assessment and blood glucose self-monitoring test results. Protein 1.1 g/kg Protein foods do not raise post-meal blood glucose levels. Add protein to meals and snacks to help provide enough calories and to satisfy appetite. Fat Limit saturated fat. Fat intake may be increased because of increased protein intake; focus on leaner protein choices. Sodium Not routinely restricted. Fiber For relief of constipation, gradually increase intake and increase fluids. Use whole grains and raw fruits and vegetables. Activity and fluids help relieve constipation. Non-nutritive sweeteners Use only FDA-approved sweeteners. Saccharin crosses the placenta but has not been shown to be harmful. Vitamins and minerals Preconception folate. Assess for specific individual needs: multivitamin throughout pregnancy, iron at 12 weeks, and calcium, especially in the last trimester and while lactating. Take prenatal vitamin. If it causes nausea, try taking at bedtime.

table on 510

moto's thyroiditis Inherited autoimmune disease; 5-10 times more common in women Presence of anti-TPO (antithyroid peroxidase) antibodies in blood Lymphocytic thyroiditis (following hyperthyroidism) Inflammation of thyroid gland; common after pregnancy, majority affected ultimately regain normal thyroid function (remaining hypothyroid is a possibility) Usually a hyperthyroid phase (excessive amounts of thyroid hormone leak from inflamed gland) followed by hypothyroid phase Thyroid destruction Secondary to radioactive iodine treatment (for Graves' disease, for example) or surgery to remove thyroid gland Little or no functioning thyroid tissue Pituitary or hypothalamic Pituitary gland or hypothalamus unable to signal thyroid gland to produce thyroid hormones; labeled secondary hypothyroidism if caused by pituitary tumors or disease, and tertiary hypothyroidism if caused by hypothalamic tumors or disease Decreased levels of T4 and T3 even if thyroid gland is normal Pituitary injury May result after brain surgery or decreased supply of blood to area; in cases of pituitary injury, TSH (produced by pituitary gland) is deficient and blood levels are low TSH levels elevated Medications Medications used to treat overactive thyroid (methimazole [Tapezole] and propylthiouracil [PTU]); psychiatric medication lithium; drugs containing large amounts of iodine (amiodarone [Cardorone], SSKI, Lugol's solution) Decreased thyroid function; low blood levels of thyroid hormone

table on 512

Endocrine Gland Hormones Target Cells Major Functions of Hormones Promotes follicular development; governs development of secondary sexual characteristics: stimulates uterine and breast growth Promotes closure of the epiphyseal plate Prepares for pregnancy Stimulates sperm production; governs development of secondary sexual characteristics; promotes sex drive Enhances pubertal growth spurt; promotes closure of the epiphyseal plate Inhibits secretion of follicle-stimulating hormone Entrains body's biological rhythm with external cues; believed to inhibit gonadotropins; initiation of puberty possibly caused by a reduction in melatonin secretion; acts as an antioxidant; enhances immunity Help maintain pregnancy; prepare breasts for lactation Maintains corpus luteum of pregnancy Stimulates aldosterone secretion Stimulates erythrocyte production Control of motility and secretion to facilitate digestive and absorptive processes Same as for gastrin Stimulates insulin secretion Promote growth Stimulates platelet production Increases absorption of ingested calcium and phosphate Enhances T lymphocyte proliferation and function Inhibits Na1 reabsorption Gonads Female: ovaries Male: testes Testes and ovaries Pineal gland Placenta Kidneys Stomach Duodenum Liver Skin Thymus Heart Estrogen (estradiol) Progesterone Testosterone Inhibin Melatonin Estrogen (estradiol); progesterone Chorionic gonadotropin Renin (→ angiotensin) Erythropoietin Gastrin Secretin; cholecystokinin Glucose-dependent insulinotropic peptide Somatomedins Thrombopoietin Vitamin D Thymosin Atrial natriuretic peptide Female sex organs; body as a whole Bone Uterus Male sex organs; body as a whole Bone Anterior pituitary Brain; anterior pituitary; reproductive organs; immune system; possibly others Female sex organs Ovarian corpus luteum Zona glomerulosa of adrenal cortex (acted on by angiotensin, which is activated by renin) Bone marrow Digestive-tract exocrine glands and smooth muscles; pancreas; liver; gallbladder Same as for gastrin Endocrine pancreas Bone; soft tissues Bone marrow Intestine T lymphocytes Kidney tubules

this is a table on 472

Hypothalamus Posterior pituitary (hormones stored in) Anterior pituitary Thyroid gland follicular cells Thyroid gland C cells Adrenal cortex zona glomerulosa Adrenal cortex zona fasciculata and zona reticularis Adrenal medulla Endocrine pancreas (islets of Langerhans) Parathyroid gland Hormones Releasing and inhibiting hormones (TRH, CRH, GnRH, GHRH, GHIH, PRH, PIH) Vasopressin (antidiuretic hormone) Oxytocin Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Growth hormone Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) (interstitial cell-stimulating hormone [ICSH]) Prolactin Tetraiodothyronine (T4 or thyroxine); triiodothyronine (T3) Calcitonin Aldosterone (mineralocorticoid) Cortisol (glucocorticoid) Androgens (dehydroepiandrosterone) Epinephrine and norepinephrine Insulin (b cells) Glucagon (a cells) Somatostatin (Δ cells) Pancreatic polypeptide (F or PP cells) Parathyroid hormone (PTH) Target Cells Anterior pituitary Kidney tubules Arterioles Uterus Mammary glands (breasts) Thyroid follicular cells Zona fasciculata and zona reticularis of adrenal cortex Bone; soft tissues Liver Females: ovarian follicles Males: seminiferous tubules in testes Females: ovarian follicle and corpus luteum Males: interstitial cells of Leydig in testes Females: mammary glands Males Most cells Bone Kidney tubules Most cells Females: bone and brain Sympathetic receptor sites throughout the body Most cells Most cells Digestive system Pancreatic islet cells Anterior pituitary gland Pancreas Bone, kidneys, intestine Major Functions of Hormones Controls release of anterior pituitary hormones Increases H2O reabsorption Produces vasoconstriction Increases contractility Causes milk ejection Stimulates T3 and T4 secretion Stimulates cortisol secretion Essential but not solely responsible for growth; stimulates growth of bones and soft tissues; metabolic effects include protein anabolism, fat mobilization, and glucose conservation Stimulates somatomedin secretion Promotes follicular growth and development; stimulates estrogen secretion Stimulates sperm production Stimulates ovulation, corpus luteum development, and estrogen and progesterone secretion Stimulates testosterone secretion Promotes breast development; stimulates milk secretion Uncertain Increases the metabolic rate; essential for normal growth and nerve development Decreases plasma calcium concentration Increases Na1 reabsorption and K1 secretion Increases blood glucose at the expense of protein and fat stores; contributes to stress adaption Responsible for the pubertal growth spurt and sex drive in females Reinforces the sympathetic nervous system; contributes to stress adaption and blood pressure regulation Promotes cellular uptake, use, and storage of absorbed nutrients Important for maintaining nutrient levels in blood during post-absorptive state Inhibits digestion and absorption of nutrients Inhibits secretion of all pancreatic hormones Controls secretion of growth hormone Plays possible role in reducing appetite and food intake by inhibiting post-prandial pancreatic exocrine secretion Increases plasma calcium concentration; decreases plasma phosphate concentration; stimulates vitamin D activation

this is a table on page 471

Table 17.11 outlines the current evidence for nutrition therapy recommendations, and Table 17.12 summarizes nutrition strategies for all persons with diabetes. Meal Patterns and Planning Numerous meal patterns dis- cussed within the literature can be used to achieve glycemic and metabolic goals. These include the Mediterranean diet, Table 17.12 Nutrition Strategies for Individuals with Diabetes Strategies for all people with diabetes: 500 Part 4 Nutrition Therapy the DASH diet, and vegetarian or vegan diets as well as low- fat and low-carbohydrate diets. Personal choice and individ- ual metabolic parameters will assist in using these patterns to make individual food choices. Registered dietitians and certi- fied diabetes educators may teach the individual with diabetes a variety of meal planning methods they can use to coordinate their food intake with their medications. Every meal planning

• Portion control should be recommended for weight loss and maintenance. • Carbohydrate-containing foods and beverages and endogenous insulin production are the greatest determinant of the post-meal blood glucose level; therefore, it is important to know what foods contain carbohydrates: starchy vegetables, whole grains, fruit, milk and milk products, vegetables, and sugar. • When choosing carbohydrate-containing foods, choose nutrient-dense, high-fiber foods whenever possible instead of processed foods with added sodium, fat, and sugars. Nutrient-dense foods and beverages provide vitamins, minerals, and other healthful substances with relatively few calories. Calories have not been added to them from solid fats, sugars, or refined starches. • Avoid sugar-sweetened beverages. • For most people, it is not necessary to subtract the amount of dietary fiber or sugar alcohols from total carbohydrates when carbohydrate counting. • Substitute foods higher in unsaturated fat (liquid oils) for foods higher in trans or saturated fat. • Select leaner protein sources and meat alternatives. • Vitamin and mineral supplements, herbal products, or cinnamon to manage diabetes are not recommended due to lack of evidence. • Moderate alcohol consumption (one drink/day or less for adult women and two drinks/day or less for adult men) has minimal acute or long-term effects on blood glucose in people with diabetes. To reduce risk of hypoglycemia for individuals using insulin or insulin secretagogues, alcohol should be consumed with food. • Limit sodium intake to 2300 mg/day. Priority should be given to coordinating food with type of diabetes medicine for those individuals on medicine. • For individuals who take insulin secretagogues: ◆ Moderate amounts of carbohydrate at each meal and snacks. ◆ To reduce risk of hypoglycemia:* ♦ Eatasourceofcarbohydratesatmeals. ♦ Moderateamountsofcarbohydratesateachmealandsnacks. ♦ Donotskipmeals. ♦ Physicalactivitymayresultinlowbloodglucosedependingonwhenitisperformed.Alwayscarryasourceofcarbohydratestoreduceriskof hypoglycemia.* ◆ For individuals who take biguanides (metformin): ◆ Gradually titrate to minimize gastrointestinal side effects when initiating use: ♦ Takemedicationwithfoodor15minutesafteramealifsymptomspersist. ♦ Ifsideeffectsdonotresolveovertime(afewweeks),followupwithhealthcareprovider. ♦ Iftakingalongwithaninsulinsecretagogueorinsulin,mayexperiencehypoglycemia.* • For individuals who take a-glucosidase inhibitors: ◆ Gradually titrate to minimize gastrointestinal side effects when initiating use. ◆ Take at start of meal to have maximal effect: ♦ Iftakingalongwithaninsulinsecretagogueorinsulin,mayexperiencehypoglycemia. ♦ Ifhypoglycemiaoccurs,eatsomethingcontainingmonosaccharidessuchasglucosetabletsasdrugwillpreventthedigestionof polysaccharides. • For individuals who take incretin mimetics (GLP-1): ◆ Gradually titrate to minimize gastrointestinal side effects when initiating use: ♦ Injectionofdailyortwice-dailyGLP-1sshouldbepre-meal. ♦ Ifsideeffectsdonotresolveovertime(afewweeks),followupwithhealthcareprovider. ♦ Iftakingalongwithaninsulinsecretagogueorinsulin,mayexperiencehypoglycemia.* ♦ Once-weeklyGLP-1scanbetakenatanytimeduringthedayregardlessofmealtimes. • For individuals with type 1 diabetes and insulin-requiring type 2 diabetes: ◆ Learn how to count carbohydrates or use another meal planning approach to quantify carbohydrate intake. The objective of using such a meal planning approach is to "match" mealtime insulin to carbohydrates consumed. ◆ If ♦ ♦ ♦ ◆ If ♦ ♦ ♦ ♦ ◆ If ♦ on a multiple-daily injection plan or on an insulin pump: Takemealtimeinsulinbeforeeating. Mealscanbeconsumedatdifferenttimes. Ifphysicalactivityisperformedwithin1-2hoursofmealtimeinsulininjection,thisdosemayneedtobeloweredtoreduceriskof hypoglycemia.* on a premixed insulin plan: Insulindosesneedtobetakenatconsistenttimeseveryday. Mealsneedtobeconsumedatsimilartimeseveryday. Donotskipmealstoreduceriskofhypoglycemia. Physicalactivitymayresultinlowbloodglucosedependingonwhenitisperformed.Alwayscarryasourceofquick-actingcarbohydratestoreduce risk of hypoglycemia.* on a fixed insulin plan: Eatsimilaramountsofcarbohydrateseachdaytomatchthesetdosesofinsulin.