Patho Ch 33 best set: Diabetes Mellitus and the Metabolic Syndrome: Hormonal Control of Nutrient Metabolism and Storage

IFG

(impaired fasting plasma glucose)

HHS signs and symptoms

-Shallow respirations -Absent deep tendon reflexes -Paresis -Positive babinski sign The most prominent manifestations are weakness, dehydration, polyuria, neurologic signs and symptoms, and excessive thirst. The neurologic signs include hemiparesis (weakness on one side of the body), Babinski reflex (the sole of the foot has been firmly stroked, the toes flex and flare out), aphasia (unable to respond verbally to questions), muscle fasciculations (uncontrollable twitching of a muscle group), hyperthermia, hemianopia, nystagmus, visual hallucinations, seizures, and coma. The onset of HHS often is insidious, and because it occurs most frequently in older people, it may be mistaken for a stroke.

Criteria for Diagnosis of Diabetes

1. A1C ≥ 6.5%. OR 2. Fasting Plasma Glucose (FPG) ≥ 126 mg/dL. OR 3. 2-hour plasma glucose ≥ 200 mg/dL during an Oral Glucose Tolerance Test (OGTT) using a 75 g glucose load. OR 4. When a patient has symptoms of a hyperglycemic crisis, a random plasma glucose of ≥ 200 mg/dL.

Normal FPG (fasting plasma glucose)

<100 mg/dL The FPG represents plasma glucose levels after food has been withheld for at least 8 hours. An FPG level below 100 mg/dL (5.6 mmol/L) is considered normal

Glucagon

A protein hormone secreted by pancreatic endocrine alpha cells that raises blood glucose levels; an antagonistic hormone to insulin.

Incretin based agents

The incretins are the dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists

diabetic foot problems

They represent the effects of neuropathy and vascular insufficiency.

what promotes glycogenolysis?

glucagon not insulin

α-glucosidase inhibitors

"Starch blockers" Slow down absorption of carbohydrate in small intestine Example Acarbose (Precose) (acarbose, miglitol) block the action of intestinal brush border enzymes that break down complex carbohy- drates. By delaying the breakdown of complex carbohydrates, the α-glucosidase inhibitors delay the absorption of carbohydrates from the gut and blunt the postprandial increase in plasma glucose and insulin levels. Although not a problem with monotherapy or combination therapy with a biguanide, hypoglycemia may occur with concur- rent sulfonylurea treatment. If hypoglycemia does occur, it should be treated with glucose (dextrose) and not sucrose (table sugar), whose breakdown may be blocked by the action of the α-glucosidase inhibitors.

Metabolic Abnormalities Involved in Type 2 Diabetes

(1) insulin resistance, (2) increased glucose production by the liver, and (3) impaired secretion of insulin by the pancreatic beta cells The metabolic abnormalities that lead to type 2 diabetes include (1) peripheral insulin resistance, (2) deranged secretion of insulin by the pancreatic beta cells, and (3) increased glucose production by the liver. In skeletal muscle, insulin resistance prompts decreased uptake of glucose.

Actions of insulin (3)

(1) it promotes glucose uptake by target cells and provides for glucose storage as glycogen; (2) it prevents fat and glycogen breakdown; and (3) it inhibits gluconeogenesis and increases protein synthesis. 1.decreases blood glucose by: a. increasing uptake of glucose b. promotes formation of glycogen c. decreases gluconeogenesis 2. decreases blood fatty acid and ketoacid concentrations a. stimulates fat deposition and inhibits lipolysis b. inhibits ketoacid formation in liver 3. decreases blood amino acid concentration a. stimulates amino acid uptake into cells, increases protein synthesis, and inhibits protein degradation decreases blood K+ 1. Facilitates transport of glucose out of the blood stream and into cells 2. Affects carb metab by increasing the use of glucose, decreases blood glucose levels, increases glycogen stores in liver and muscle 3. Affects fat metabolism by increasing formation of lipids from fatty acids, promotes fat storage in adipose tissue 4. increases protein storage and synthesis

Signs and symptoms of diabetes are often referred to as the three polys:

(1) polyuria (i.e., excessive urination), (2) polydipsia (i.e., excessive thirst), and (3) polyphagia (i.e., excessive hunger).

Hyperglycemic Hyperosmolar State (HHS)

*Usually Type 2 DM *Profound dehydration *Glucose may be >600 *Small ketonuria and absent-to-low ketonemia *pH greater than 7.30 *Bicarbonate concentration greater than 15 mEq/L characterized by hyperglycemia (blood glucose >600 mg/dL, hyperosmolarity (plasma osmolarity >320 mOsm/L) and dehydration, the absence of ketoacidosis, and depression of the sensorium. Hyperglycemic hyperosmolar state may occur in various conditions, including type 2 diabetes, acute pancreatitis, severe infection, myocardial infarction, and treatment with oral or parenteral nutrition solutions. It is seen most frequently in people with type 2 diabetes. A partial or relative insulin deficiency may initiate the syndrome by reducing glucose utilization while inducing a glucagon-stimulated increase in hepatic glucose output. With massive glycosuria, obligatory water loss occurs. If the person is unable to maintain adequate fluid intake because of associated acute or chronic illness or has excessive fluid loss, dehydration develops. As the plasma volume contracts, renal insufficiency develops and the resultant limitation of renal glucose losses leads to increasingly higher blood glucose levels and an increase in severity of the hyperosmolar state. the increased serum osmolarity has the effect of pulling water out of body cells, including brain cells.

Glucocorticoid hormones

-Direct effects on carbohydrate metabolism -Anti-inflammatory and growth-suppressing effects -Influence awareness and sleep habits -Most potent naturally occurring glucocorticoid is cortisol

somatic neuropathy s/s

-diminished perception of vibration, pain, and temp -hypersensitivity to light touch; occasionally severe "burning" pain Both legs appear to be the same as far as numbness is involved. Bilateral cool ankles and feet. With eyes closed, the client cannot identify where the HCP is touching his feet.

insulin secretagogues

-sulfonylurea; meglitinides (Glucotrol) PROMOTE INSULIN SECRETION act at the level of the pancreatic beta cells to stimulate insulin secretion. There are two general classes of insulin secretagogues: (1) sulfonylureas and (2) meglitinides. Both types require the presence of functioning beta cells, are used only in the treatment of type 2 diabetes, and have the potential for producing hypoglycemia. The sulfonylureas (e.g., glipizide, glyburide, glimepiride) act by binding to a high-affinity sulfonylurea receptor on the beta cell that is linked to an ATP-sensitive potassium channel. Binding of a sulfonylurea closes the channel, resulting in a coupled reaction that leads to an influx of calcium ions and insulin secretion. The meglitinides (repaglinide) and related drugs (nat- eglinide) are shorter-acting insulin secretagogues (termed glinides) that target post-prandial glucose elevation. These agents, which are rapidly absorbed from the gas- trointestinal tract, are taken shortly before meals. Both drugs can produce hypoglycemia; thus, proper timing of meals in relation to drug administration is essential.

casual Blood glucose test indicating diabetes

A casual (or random) plasma glucose is one that is done without regard to the time of the last meal. A casual plasma glucose concentration that is unequivocally elevated (≥200 mg/dL [11.1 mmol/L]) in the presence of classic symptoms of diabetes such as polydipsia, polyphagia, polyuria, and blurred vision is diagnostic of diabetes mellitus at any age.

somatic peripheral neuropathies

A distal symmetric polyneuropathy, in which loss of function typically occurs in a stocking-glove pattern, is the most common form of peripheral neuropathy. Somatic sensory involvement usually occurs first, often is bilateral and symmetric, and is associated with diminished perception of vibration, pain, and temperature, particularly in the lower extremities. In addition to the discomforts associated with the loss of sensory or motor function, lesions in the peripheral nervous system predispose a person with diabetes to other complications. The loss of feeling, touch, and position sense increases the risk of falling. Impairment of temperature and pain sensation increases the risk of serious burns and injuries to the feet. Denervation of the small muscles of the foot result in clawing of the toes and displacement of the submetatarsal fat pad ante- riorly. These changes, together with joint and connective tissue changes, alter the biomechanics of the foot, increasing plantar pressure and predisposing to development of foot trauma and ulcers.

Prediabetes Lab Values

A1C 5.7-6.4% Persons with IFG defined by an elevated FPG of 100 to 125 mg/dL) and/or IGT (impaired glucose tolerance [IGT] plasma glucose levels of 140 to 199 mg/dL with an OGTT) are often referred to as having prediabetes, meaning they are at relatively high risk for the future development of diabetes as well as cardiovascular disease.

diabetes mellitus (DM)

Abnormality in blood glucose regulation and nutrient storage related to an absolute or relative deficiency of insulin and/or resistance to the actions of insulin. Metabolic disorder caused by the absence or insufficient production of insulin secreted by the pancreas, resulting in hyperglycemia and glucosuria (resulting from defects in insulin secretion, insulin action, or both) An endocrine disorder marked by an inability to maintain glucose homeostasis. The type 1 form results from autoimmune destruction of insulin-secreting cells; treatment usually requires daily insulin injections. The type 2 form most commonly results from reduced responsiveness of target cells to insulin; obesity and lack of exercise are risk factors. Diabetes is a disorder of carbohydrate, protein, and fat metabolism resulting from a lack of insulin avail- ability or a reduction in the biologic effects of insulin. It can represent an absolute insulin de ciency, impaired release of insulin by the pancreatic beta cells, inadequate or defective insulin receptors or postreceptor regulation, or the production of inactive insulin or insulin that is destroyed before it can carry out its action.

alcohol consumption affect on glucose in diabetics

Alcohol decreases liver gluconeogenesis, and people with diabetes need to be cautioned about its potential for causing hypoglycemia, especially if it is consumed in large amounts or on an empty stomach.

gestational diabetes

Any degree of glucose intolerance that develops during pregnancy that is not clearly diabetes (either type 1 or type 2). caused by Combination of insulin resistance and impaired insulin secretion.

diagnostic criteria for metabolic syndrome

At least three of the following: Fasting glucose of 110 or greater abdominal obesity men > 40 inches, > 35 inches women Serum triglyceride level > or equal to 150mg/dL HDL < 40 men , < 50 women BP > or equal to 130/85 mm Hg

DKA treatment

Begin a loading dose of IV regular insulin followed by a continuous insulin infusion. High IV flow rate (150-200hr) with insulin R in prescribed mixture (Rehydrate and push K back into cell, Oxygenate) The goals in treating DKA are to improve circulatory volume and tissue perfusion, decrease blood glucose, and correct the acidosis and electrolyte imbalances. administration of insulin and intravenous fluid and electrolyte replacement solutions. Because insulin resistance accompanies severe acidosis, low-dose insulin therapy is used. An initial loading dose of short-acting (i.e., regular) or rapid-acting insulin often is given intravenously, followed by continuous low-dose short-acting insulin infusion. Frequent laboratory tests are used to monitor blood glucose and serum electrolyte levels and to guide fluid and electrolyte replacement. It is important to replace fluid and electrolytes and correct pH while bringing the blood glucose concentration to a normal level. Too rapid a drop in blood glucose may cause hypoglycemia that can occur with a large dose of regular insulin. A sudden change in the osmolality of extracellular fluid can also occur when blood glucose levels are lowered too rapidly, and this can cause cerebral edema. Serum potassium levels often fall as acidosis is corrected and potassium moves from the extracellular into the intracellular compartment. Thus, it may be necessary to add potassium to the intravenous infusion. Identification and treatment of the underlying cause, such as infection, also are important. The client may require bicarbonate, but glucose levels are lowered with insulin in this emergency situation, not by oral medication.

pathophysiologic processes underlies type 2 diabetes

Beta cell exhaustion due to long-standing insulin resistance

risk factors for foot ulcers in diabetics

Bilateral distal loss of pain sensation. Motor neuropathy related to improperly fitted shoes Smoking history averaging 2 packs/day. Distal symmetric neuropathy is a major risk factor for foot ulcers. People with sensory neuropathies have impaired pain sensation and often are unaware of the constant trauma to the feet caused by poorly fitting shoes, improper weight bearing, hard objects or peb- bles in the shoes, or infections such as athlete's foot. Neuropathy may prevent people from detecting pain; they are unable to adjust their gait to avoid walking on an area of the foot where pressure is causing trauma and necrosis. Motor neuropathy with weakness of the intrinsic muscles of the foot may result in foot deformities, which lead to focal areas of high pressure. When the abnormal focus of pressure is coupled with loss of sensation, a foot ulcer can occur. Smoking should be avoided because it causes vasoconstriction and contributes to vascular disease.

SGLT2 inhibitors

Canagliflozin (Invokana) Dapagliflozin (Farxiga) Empagliflozin (Jardiance) canagliflozin. This agent, which works by inhibiting glucose reabsorption from the kidney, results in about 70 g (approximately 300 Kcal) glucose loss per day. The adverse effects are understandable, including polyuria due to osmotic diuresis and increased urinary tract infections and genitourinary Candida infections.

common infections in diabetics

Certain types of infections occur with increased frequency in people with diabetes: soft tissue infections of the extremities, osteomyelitis, urinary tract infections and pyelonephritis, candidal infections of the skin and mucous surfaces, dental caries and periodontal disease, and tuberculosis. Suboptimal response to infection in a person with diabetes is caused by the presence of chronic complications, such as vascular disease and neuropathies, poorly controlled hyperglycemia, and altered immune cell and neutrophil function. Sensory deficits may cause a person with diabetes to ignore minor trauma and infection, and vascular disease may impair circulation and delivery of blood cells and other substances needed to produce an adequate inflammatory response and effect healing.

The destruction of beta cells and absolute lack of insulin in people with type 1 diabetes mellitus mean that they are particularly prone to the development of

DKA

Macrovascular complications

Diabetes mellitus is a major risk factor for atheroscle- rotic coronary artery disease, cerebrovascular disease, and peripheral vascular disease. The prevalence of these macrovascular complications is increased two- to four- fold in people with diabetes. Multiple risk factors for macrovascular disease, including obesity, hypertension, hyperglycemia, hyper- insulinemia, hyperlipidemia, altered platelet function, endothelial dysfunction, systemic in ammation (as evidenced by increased CRP), and elevated brinogen levels, frequently are found in people with diabetes. There appear to be differences between type 1 and type 2 diabetes in terms of duration and development of macrovascular disease, with type 2 diabetics more com- monly manifesting macrovascular disease at the time of diagnosis. This greater prevalence has been attributed to the associated cardiovascular risk factors that are part of the metabolic syndrome and which may have been present for many years before the diagnosis of type 2 diabetes. Aggressive management of cardiovascular risk factors should include smoking cessation, lifestyle changes including weight loss, and measures to control blood lipids, hypertension, and blood glucose, as appropri- ate. Antiplatelet agents (aspirin or clopidogrel) may be prescribed to reduce the threat of blood clots. If treatment is warranted for peripheral arterial disease, the peroneal arteries between the knees and ankles commonly are involved in diabetes, making revascular- ization difficult.

Chronic complications of DM

Diabetic neuropathies- effects nerve ending microvascular disease- little blood vessels macrovascular disease infection all related to chronic hyperglycemia leads to cell injury in blood vessels and nerves include disorders of the microvasculature (i.e., neuropathies, nephropathies, and retinopathies), macrovascular complications (i.e., coronary artery, cerebrovascular, and peripheral arterial disease), and foot ulcers.

prevention and treatment of diabetic nephropathy

Diet, exercise, and prescriptions to lower blood pressure below 140/80 mm Hg. Both systolic hypertension and diastolic hypertension accelerate the progression of diabetic nephropathy. Even moderate lowering of blood pressure can decrease the risk of chronic kidney disease. glycemic control, maintenance of blood pressure control (<140/80 mm Hg), prevention or reduction in the level of proteinuria (using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or protein restriction in selected patients), treatment of hyperlipidemia, and smoking cessation in people who smoke. Smoking increases the risk of CKD in both persons with and without diabetes. People with type 2 diabetes who smoke have a greater risk of increased urinary albumin excretion, and their rate of progression to CKD is approximately twice as rapid as in those who do not smoke.

Islet of Langerhans in the pancreas

Each islet is composed of: beta cells that secrete insulin and amylin, alpha cells that secrete glucagon, and delta cells that secrete somatostatin. Blood glucose regulation is also influenced by several gut-derived hormones that increase insulin release after nutrient intake and by counterregulatory hormones that help to maintain blood glucose levels during periods of limited glucose intake or excessive glucose use.

Dawn phenomenon

Early morning glucose elevation produced by the release of growth hormone, which decreases peripheral uptake of glucose resulting in elevated morning glucose levels. Admin of insulin at a later time in day will coordinate insulin peak with the hormone release. The dawn phenomenon is characterized by increased levels of fasting blood glucose, or insulin requirements, or both, between 5 AM and 9 AM without antecedent hypoglycemia. It occurs in people with type 1 or type 2 diabetes. It has been suggested that a change in the normal circadian rhythm for glucose tolerance, which usually is higher during the latter part of the morning, is altered in people with diabetes. Growth hormone has been suggested as a possible factor. abnormal nighttime growth hormone secretion as a possible factor. When the dawn phenomenon occurs alone, it may produce only mild hyperglycemia, but when it is combined with the Somogyi effect, it may produce profound hyperglycemia.

Incretin Mimetics

Exenatide, liraglutide, albiglutide, dulaglutide Incretins are hormones released into the circulation by the gastrointestinal tract after a meal, especially one high in carbohydrates, that amplify the glucose-induced release of insulin. The main incretins secreted are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both GLP-1 and GIP are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 enzyme inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels, which then increase insulin release. Glucagon-like peptide 1 also helps to suppress glucagon release. Exenatide, a synthetic analog of GLP-1 that is resistant to DPP-4 degradation, is approved as an injectable adjunctive therapy for people with type 2 diabetes. The drug has been shown to have multiple actions such as potentiation of glucose-mediated insulin release, slowed gastric emptying, and a central loss of appetite.

normal labs for blood glucose

FPG‡ N o r m o g l y c e m i a<100 mg/dL 2-h plasma glucose in 75-g OGTT <140 mg/dL(7.8 mmol/L) A1C: 3.9%-5.6%

Criteria for Diagnosis of Diabetes

FPG≥126mg/dL(7.0mmol/L) or OGTT≥200mg/dL(11.1mmol/L) or A1C≥6.5% or hyperglycemia or hyperglycem ic crisis and a plasma glucose ≥200 mg/dL (11.1 mmol/L)

nutritional goals for diabetes

For a person with type 1 diabetes, eating consistent amounts and types of food at specific and routine times is encouraged. Home blood glucose monitoring is used to fine-tune the plan. Most people with type 2 diabetes are overweight; thus nutrition therapy focuses on achieving glucose, lipid, and blood pressure goals, and weight loss if indicated. Mild to moderate weight loss (5% to 10% of total body weight) has been shown to improve diabetes control

DKA signs and symptoms

Fruity breath (from acetone), dry mucous membranes from polyuria Deep respirations possibly kussmaul respirations Drowsiness, stupor or coma Low BP from polyuria Glucosuria, ketonuria, Polyuria and polydipsia, n/v, not necessarily hunger Glucose at 300-800mg/dl The development of DKA is commonly preceded by a day or more of polyuria, polydipsia, nausea, vomiting, and marked fatigue, with eventual stupor that can prog- ress to coma. Abdominal pain and tenderness may be experienced without abdominal disease. The breath has a characteristic fruity smell because of the presence of volatile ketoacids. Hypotension and tachycardia may be present because of a decrease in blood volume. A number of the signs and symptoms that occur in DKA are related to compensatory mechanisms. The heart rate increases as the body compensates for a decrease in blood vol- ume, and the rate and depth of respiration increase (i.e., Kussmaul respiration) as the body attempts to prevent further decreases in pH .

Growth Hormone

Growth hormone has many met- abolic effects. It increases protein synthesis in all cells of the body, mobilizes fatty acids from adipose tissue, and antagonizes the effects of insulin. Growth hormone decreases cellular uptake and use of glucose, thereby increasing the level of blood glucose. The increased blood glucose level stimulates further insulin secretion by the beta cells. The secretion of growth hormone normally is inhibited by insulin and increased levels of blood glucose. During periods of fasting, when both blood glucose levels and insulin secretion fall, growth hormone levels increase. Exercise, such as running and cycling, and various stresses, including anesthesia, fever, and trauma, also increase growth hormone levels. Chronic hypersecretion of growth hormone, such as occurs in acromegaly, can lead to glucose intolerance and the development of diabetes mellitus. In people who already have diabetes, moderate elevations in growth hormone levels that occur during periods of stress and periods of growth in children can produce the entire spectrum of metabolic abnormalities associated with poor regulation, despite optimized insulin treatment.

metabolic syndrome

Hyperglycemia in diabetics with insulin resistance is frequently associated with intra-abdominal obesity, high levels of plasma triglycerides and low levels of high-density lipoproteins (HDLs), hypertension, systemic in flammation (as detected by C-reactive protein [CRP] and other mediators), abnormal fibrinolysis, abnormal function of the vascular endothelium, and macrovascular disease (coronary artery, cerebrovas- cular, and peripheral arterial disease). This constellation of abnormalities often is referred to as the insulin resis- tance syndrome, syndrome X, or, the preferred term, metabolic syndrome.

Categories of Increased Risk for Diabetes

Impaired fasting glucose (IFG)100 mg/dL(5.6 mmol/L) to 125 mg/dL(6.9 mmol/L) Impaired glucose tolerance (IGT) 140mg/dL(7.8mmol/L) to 199 mg/dL(11.0 mmol/L) A1C 5.7%-6.4%

autonomic peripheral neuropathies classification

Impaired vasomotor function: Postural hypotension Impaired gastrointestinal function: Gastric atony Diarrhea, often postprandial and nocturnal Impaired genitourinary function: Paralytic bladder Incomplete voiding Erectile dysfunction Retrograde ejaculation Cranial nerve involvement: Extraocular nerve paralysis Impaired pupillary responses Impaired special senses

ED in diabetes

In the male, disruption of sensory and autonomic ner- vous system function may cause sexual dysfunction . Diabetes is the leading pathophysiological cause of erectile dysfunction (ED), and it occurs in both type 1 and type 2 diabetes.

Diabetes Mellitus, four clinical classes

Included are the categories of type 1 diabetes (i.e., diabetes resulting from beta cell destruction and an absolute insulin deficiency); type 2 diabetes (i.e., diabetes due to insulin resistance and a relative insulin deficiency); gestational diabetes mellitus (i.e., glucose intolerance that develops during pregnancy that is not clearly overt diabetes [either type 1 or type 2]); and other specific types of diabetes, many of which occur secondary to other conditions (e.g., Cushing syndrome, acromegaly, and pancreatitis). Person with a FPG greater than or equal to 126 mg/dL (7.0 mmol/L) or an OGTT 2-hour glucose level greater than or equal to 200 mg/dL (11.1 mmol/L) are considered to have provisional diabetes. diagnosis of diabetes, with an A1C threshold of greater than 6.5% .

HHS treatment

Insulin: lower BG slowly (no more than 75-100 mg/dL/hr to prevent cerebral edema) replace fluids w hypotonic solutions The treatment of HHS requires judicious medical observation and care as water moves back into brain cells, posing a threat of cerebral edema. Extensive potassium losses that also have occurred during the diuretic phase of the disorder require correction. Because of the problems encountered in the treatment and the serious nature of the disease conditions that cause HHS, the prognosis for this disorder is less favorable than that for ketoacidosis.

One of the first manifestations of diabetic nephropathy is

Microalbuminuria an increase in urinary albumin excretion, which is defined as a urine protein loss greater or equal to 30 mg/day or an albumin-to-creatinine ratio (A/C ratio) greater or equal to 30 μg/mg (normal <30 μg/mg) from a spot urine collection. It is recommended that the A/C ratio be the preferred screen for increased urinary albumin excretion. Both systolic and diastolic forms of hypertension accelerate the progression of diabetic nephropathy. Even moderate lowering of blood pressure can decrease the risk of CKD. The estimated glomerular filtration rate (eGFR) should also be monitored on a regular basis. Risk factors, rather than renal manifestations, include glycosylated hemoglobin levels greater than 8.1%, genetic and familial predisposition, hypertension, poor glycemic control, smoking, and hyperlipidemia. Usually, serum potassium levels are elevated (hyperkalemia) in diabetic nephropathy.

increased risk of GDM

Obesity is among the risk factors for gestational diabetes mellitus (GDM). Obstetric complications, multiple pregnancies, high triglycerides, and hypertension are not specific risk factors for GDM.

OGTT

Overnight fasting, avoid caffeine, no smoking for 12 hours prior to test, fasting glucose is obtained, 100 g glucose load is given, and serum glucose levels are determined at 1, 2, and 3 hours following ingestion

impaired fasting plasma glucose (IFG) and/or impaired glucose tolerance (IGT).

Persons whose glucose levels, although not meeting the criteria for diabetes, are too high to be considered normal. IFG is defined by an elevated FPG of 100 to 125 mg/dL and IGT as plasma glucose levels of 140 to 199 mg/dL with an OGTT. Persons with IFG and/or IGT are often referred to as having prediabetes, meaning they are at relatively high risk for the future development of diabetes as well as cardiovascular disease. Thus, calorie restriction and weight reduction (even 5% to 10%) are important in overweight people with prediabetes.

somatic diabetic neuropathy classification

Polyneuropathies (bilateral sensory): Paresthesias, including numbness and tingling Impaired pain, temperature, light touch, two-point discrimination, and vibratory sensation Decreased ankle and knee-jerk reflexes Mononeuropathies: Involvement of a mixed nerve trunk that includes loss of sensation, pain, and motor weakness Amyotrophy: Associated with muscle weakness, wasting, and severe pain of muscles in the pelvic girdle and thigh

Epinephrine (adrenaline)

Produced by adrenal medulla. Targets liver, muscle, and adipose tissue to raise blood level of sugar and fatty acids; increases heart rate and force of contraction.

insulin types (4)

Rapid-acting (clear) , Short-acting (clear), Intermediate (cloudy), Long acting , Combination Four insulin types are classfied by length and peaking of action: short acting, rapid acting, intermediate act- ing, and long acting. Short-acting insulin (regular) is a soluble crystalline insulin whose effects begin within 30 minutes after subcutaneous injection and generally last for 5 to 8 hours. The rapid-acting insulins (lispro, aspart, glulisine) are produced by recombinant technology and have a more rapid onset, peak, and duration of action than short-acting regular insulin. The rapid-acting insulins, which are used in combination with intermediate or long-acting insulins, are usually administered immediately before a meal. Intermediate- to long-acting insulins (neutral protamine Hagedorn [NPH], glargine, and detemir) have slower onsets and a longer duration of action. They require several hours to reach therapeutic levels, so their use in type 1 diabetes requires supplemen- tation with rapid- or short-acting insulin. All forms of insulin have the potential to produce hypoglycemia or "insulin reaction" as a side effect

II. Diabetes Mellitus 1. Classification and Etiology a. Categories of Risk for Diabetes b. Type 1 Diabetes Mellitus c. Type 2 Diabetes Mellitus and the Metabolic Syndrome d. Other Specific Types of Diabetes e. Gestational Diabetes 2. Clinical Manifestations of Diabetes 3. Diagnostic Tests a. Blood Tests b. Urine Tests 4. Diabetes Management a.Dietary Management b. Exercise c. Oral and Injectable Antidiabetic Agents d. Insulin e. Pancreas or Islet Cell Transplantation f. Management of Diabetes in Children 5. Acute Complications a. Diabetic Ketoacidosis b.Hyperglycemic Hyperosmolar State c. Hypoglycemia 6. The Somogyi Effect and Dawn Phenomenon 7. Chronic Complications a. Theories of Pathogenesis b. Diabetic Neuropathies c. Diabetic Nephropathies d. Diabetic Retinopathies e. Macrovascular Complications f. Diabetic Foot Ulcers g. Infections

SUMMARY CONCEPTS Diabetes mellitus is a disorder of carbohydrate, protein, and fat metabolism resulting from an imbalance between insulin availability and insulin need. In type 1 diabetes, there is destruction of beta cells and an absolute insulin deficiency.Type 2 diabetes is characterized by a lack of insulin availability or effectiveness. Diabetes can also occur secondary to some other condition that destroys beta cells (e.g., pancreatic disorders) or endocrine diseases that cause increased production of glucose by the liver and decreased use of glucose by the tissues (e.g., Cushing syndrome). Gestational diabetes develops during pregnancy. The metabolic syndrome represents a constellation of metabolic abnormalities characterized by obesity, insulin resistance, high triglyceride levels and low HDL levels, hypertension, cardiovascular disease, and increased risk for development of type 2 diabetes. The most commonly identified symptoms of type 1 diabetes are polyuria, polydipsia, polyphagia, and weight loss despite normal or increased appetite. Although persons with type 2 diabetes may present with one or more of these symptoms, they are often asymptomatic initially. The diagnosis of diabetes mellitus is based on clinical signs of the disease, fasting blood glucose levels, random plasma glucose measurements, and results of the glucose tolerance test. Glycosylation involves the irreversible attachment of glucose to the hemoglobin molecule; the measurement of glycosylated hemoglobin (A1C) provides an index of blood glucose levels over several m onths. Self-monitoring of capillary blood glucose provides a means of maintaining near-normal blood glucose levels through adjustment of insulin dosage. Dietary management of diabetes focuses on maintaining a well-balanced diet, controlling calories to achieve and maintain an optimum weight, and regulating the distribution of carbohydrates, proteins, and fats. Pharmacologic agents used in the management of diabetes include injectable insulin, injectable non-insulin agents including amylin and GLP-1 analogs, and oral diabetic drugs. Type 1 diabetes (and sometimes type 2 diabetes) requires treatment with injectable insulin. Oral antidiabetic drugs include the insulin secretagogues, biguanides, α-glucosidase inhibitors, thiazolidinediones, and incretin-based therapies. These drugs require a functioning pancreas and may be used in the treatment of type 2 diabetes. The metabolic disturbances associated with diabetes affect almost every body system. The acute complications of diabetes include diabetic ketoacidosis, hyperglycemic hyperosmolar state, and hypoglycemia in people with insulin-treated diabetes.The chronic complications of diabetes affect the microvascular system (including the retina, kidneys, and peripheral nervous system) and the macrovascular system (coronary, cerebrovascular, and peripheral arteries). The diabetic foot is usually a combination of both microvascular and macrovascular dysfunction. Infection is also a frequent occurrence and is more likely to be severe in the diabetic patient.

topics: I. Hormonal Control of Nutrient Metabolism and Storage 1. Nutrient Metabolism and Storage a. Glucose Metabolism and Storage b. Fat Metabolism and Storage c. Protein Metabolism and Storage 2. Glucose-Regulating Hormones a. Insulin b. Glucagon c. Amylin, Somatostatin, and Gut-Derived Hormones d.. Counterregulatory Hormones

SUMMARY CONCEPTS The body predominantly metabolizes glucose and fatty acids for energy.The brain depends exclusively on glucose for its energy. The liver stores excess glucose as glycogen. Fats, which serve as an ef cient source of fuel for the body, are stored in adipose tissue as triglycerides, which consist of three fatty acids linked to a glycerol molecule. In situations that favor fat breakdown, such as fasting or diabetes mellitus, the triglycerides in adipose tissue are broken down and the fatty acids are used as fuel or transported to the liver, where they are converted to ketones. Proteins, which are made up of amino acids, are essential for the formation of all body structures. Unlike glucose and fatty acids, there is onlya lim ited facility for storage of excess amino acids in the body. Because fatty acids cannot be converted to glucose, the body must break down proteins and use the amino acids for gluconeogenesis. Energy metabolism is controlled by a number of hormones, including insulin, glucagon, epinephrine, growth hormone, and the glucocorticoids. Of these hormones, only insulin has the effect of lowering the blood glucose level. It does this by facilitating the transport of glucose into body cells and decreasing the liver's production and release of glucose into the bloodstream. Insulin also has the effect of decreasing lipolysis and the use of fats as a fuel source. Other hormones—glucagon, epinephrine, growth hormone, and the glucocorticoids—maintain or increase blood glucose concentrations. Glucagon and epinephrine prom ote glycogenolysis, and glucagon and the glucocorticoids increase gluconeogenesis. Epinephrine and glucagon also increase the use of fat for energy by increasing the release of fatty acids from adipose tissue cells. Growth hormone decreases the peripheral utilization of glucose.

insulin levels in response to food

Serum insulin levels begin to rise within minutes after a meal, reach a peak in approximately 3 to 5 minutes, and then return to baseline levels within 2 to 3 hours.

medication that affect insulin

Several diuretics—thiazide and loop diuretics—can elevate blood glucose. These diuretics increase potas- sium loss, which is thought to impair beta cell release of insulin. Other drugs and therapies known to cause hyperglycemia include diazoxide, glucocorticoids, oral contraceptives, antipsychotic agents, and total paren- teral nutrition (i.e., hyperalimentation). glucocorticoids (which can increase insulin resistance) and certain immunosuppressants such as cyclosporine (which are beta-cell toxic)

Diabetic Ketoacidosis (DKA)

Shortage of insulin resulting in hyperglycemia and production of ketones. characterized by hyperglycemia, ketosis, and metabolic acidosis, is an acute life- threatening complication of uncontrolled diabetes. Diabetic ketoacidosis primarily affects persons with type 1 diabetes, but may also occur in persons with type 2 diabetes when severe stress such as sepsis or trauma is present. It may be an initial manifestation of previously undiagnosed type 1 diabetes or may result from increased insulin requirements in type 1 diabetes during stress situations, such as infection or trauma, that increase the release of stress hormones. A lack of insulin results in the rapid breakdown of energy stores from muscle and fat deposits, leading to increased movement of amino acids to the liver for conversion to glucose and of fatty acids for conversion to ketones. In the presence of ketosis, the levels of glucagon and counterregulatory hormones (i.e., glucocorticosteroids, epinephrine, and growth hor- mone) are consistently increased. Furthermore, in the absence of insulin, peripheral utilization of glucose and ketones is reduced. Metabolic acidosis is caused by the excess ketoacids that require buffering by bicarbonate ions; this leads to a marked decrease in serum bicarbonate levels. associated with very low insulin levels and extremely high levels of glucagon, catecholamines, and other counterregulatory hormones. Increased levels of glucagon and the catecholamines lead to mobilizationof substrates for gluconeogenesis and ketogenesis by the liver. Gluconeogenesis in excess of that needed to supply glucose to the brain and other glucose- dependent tissues produces a rise in blood glucose levels. Mobilization of free fatty acids (FFAs) from triglyceride stores in adipose tissue leads to accelerated ketone production and ketosis.

The Somogyi Effect and Dawn Phenomenon

Somogyi effect: -Occurs during sleep hours -Characterized by headaches on awakening, night sweats, or nightmares -Treatment is less insulin *A high does of insulin produces decline in BG levels during the night which causes release of glucagon, epinephrine, growth hormone, cortisol which stimulates lipolysis, gluconeogenesis and glycogenolysis = rebound hyperglycemia Dawn phenomenon: -Detected on awakening -Most severe when growth hormone peaks (adolescence and young adulthood) -Treatment - adjust timing of insulin administration or increase insulin. these result from the mobilization of counterregulatory hormones, contribute to difficulties with diabetic control.

diabetes that is associated with certain other conditions and syn- dromes

Such diabetes can occur with pancreatic disease or removal of pancreatic tissue and with other endocrine diseases, such as acromegaly, Cushing syndrome, or pheochromocytoma. Endocrine disorders that produce hyperglycemia do so by increasing the hepatic produc- tion of glucose or decreasing the cellular use of glucose. Cystic fibrosis-related diabetes (CFRD) is now recognized as the most common com-plication of cystic fibrosis

when to test for diabetes

Testing for diabetes should be considered in all individuals 45 years of age and older. Diabetes screen- ing should be considered at a younger age in people who are obese, have a rst-degree relative with diabetes, are members of a high-risk group, have delivered an infant weighing more than 9 pounds or been diagnosed with GDM, have hypertension or hyperlipidemia, or have met the criteria (IFG, IGT, elevated A1C) for increased risk of diabetes on previous testing.

autonomic neuropathy

The autonomic neuropathies involve disorders of sympathetic and parasympathetic nervous system function. There may be disorders of vasomotor function, decreased cardiac responses, inability to empty the bladder, gastrointestinal motility problems, and sexual dysfunction. Defects in vasomotor reflexes can lead to dizziness and syncope due to postural hypotension when the person moves from the supine to the standing position. Incomplete emptying of the bladder predisposes to urinary stasis and bladder infection and increases the risk of renal complications. Gastrointestinal motility disorders are common in persons with long-standing diabetes. The symptoms vary in severity and include gastroparesis, constipation, diarrhea, and fecal incontinence. Gastroparesis (delayed emptying of stomach) is commonly seen in persons with diabetes.55 The disorder is characterized by complaints of epigastric discomfort, nausea, postprandial vomiting, bloating, and early satiety. Abnormal gastric empty- ing also jeopardizes the regulation of the blood glucose level. Diarrhea is another common symptom seen mostly in persons with poorly controlled type 1 diabetes and autonomic neuropathy.

DKA diagnosis

The definitive diagnosis of DKA consists of hyperglycemia (blood glucose levels >250 mg/dL, low serum bicarbonate, low arterial pH, and positive urine and serum ketones. It can be further subdivided into mild DKA (serum bicarbonate of 15 to 18 mEq/dL , pH 7.25 to 7.30); moderate DKA (serum bicarbonate 10 to <15 mEq/dL, pH 7.00 to 7.24); and severe DKA (serum bicarbonate <10 mEq/dL, pH <7.00). Hyperglycemia leads to osmotic diuresis, dehydration, and a critical loss of electrolytes. Hyperosmolality of extracellular fluids from hyperglycemia leads to a shift of water and potassium from the intracellular to the extracellular

Gluconeogenesis

The formation of glucose from noncarbohydrate sources, such as amino acids. the liver synthesizes glucose from amino acids, glycerol, and lactic acid. This glucose may be released directly into the circulation or stored as glycogen. liver converts amino acids, lactate, and glycerol into glucose during fasting or when glucose intake does not keep pace with demand. Because fatty acids cannot be converted to glucose, the body must break down proteins and use the amino acids as a major substrate for formation of glucose during periods when metabolic needs exceed food intake.

Glucocorticoid Hormones

The glucocorticoid hor- mones, which are synthesized in the adrenal cortex along with other corticosteroid hormones, are critical to survival during periods of fasting and starvation. They stimulate gluconeogenesis by the liver, sometimes producing a 6- to 10-fold increase in hepatic glucose production. These hormones also moderately decrease tissue use of glucose. There are several steroid hormones with glucocor- ticoid activity; the most important of these is cortisol, which accounts for approximately 95% of all gluco- corticoid activity. Almost any type of stress, whether physical or emotional, causes an imme- diate increase in adrenocorticotropic hormone (ACTH) secretion by the anterior pituitary gland, followed within minutes by greatly increased secretion of cortisol by the adrenal gland. Hypoglycemia is a potent stimulus for cortisol secretion. In predisposed persons, the prolonged elevation of glucocorticoid hormones can lead to hyper- glycemia and the development of diabetes mellitus. In people with diabetes, even transient increases in cortisol can complicate control.

Elevated FFA (free fatty acids) in type 2 diabetes

This may increase the amount of triglyceride (a form of fat) stored in the liver or around the heart. The pancreas is affected by increased fat (lipotoxicity), which causes beta cell dysfunction, leading to the need for insulin. Visceral obesity is accompanied by an increase in postprandial FFA concentrations and subsequent triglyceride storage, including in sites that do not normally store fat such as the liver, skeletal muscle, heart, and pancreatic beta cells. A consequence to this may be a direct cause of pancreatic beta cell dysfunction (lipotoxicity). The accumulation of FFAs and triglycerides reduces hepatic insulin sensitivity, leading to increased hepatic glucose production and hyperglycemia. In the liver, the uptake of FFAs from the portal blood can lead to hepatic triglyceride accumulation and nonalcoholic fatty liver disease.

NCEP ATP III Criteria for a Diagnosis of Metabolic Syndrome

Three or more of the following: Abdominal obesity: waist circumference >35 inches (88 cm) in women or >40 inches (102 cm) in men Triglycerides: ≥ 150mg/dL (1.7mmol/L) High-density lipoproteins (HDL): <50 mg/dL (1.3 mmol/L)in women or <40 mg/dL(1.0 mmol/L) in men Blood pressure: >130/85mmHg Fasting plasma glucose: >100mg/dL (5.6mmol/L)

role of adipose tissue in DM

Visceral obesity is accompanied by an increase in postprandial FFA concentrations and subsequent triglyceride storage, including in sites that do not normally store fat such as the liver, skeletal muscle, heart, and pancreatic beta cells. First, excessive and chronic elevation of FFAs can directly cause pancreatic beta cell dysfunction (lipotoxicity). Second, at the level of the peripheral tissues, FFAs inhibit glucose uptake and glycogen storage. Third, the accumulation of FFAs and triglycerides reduces hepatic insulin sensitivity, leading to increased hepatic glucose production and hyperglycemia, especially in the fasting state. In the liver, the uptake of FFAs from the por- tal blood can lead to hepatic triglyceride accumulation and nonalcoholic fatty liver disease.

HHS s/s of water pulled from the brain cells

Weakness one side of the body After the sole of the foot has been firmly stroked, the toes flex and flare out. Unable to respond verbally to questions Uncontrollable twitching of a muscle group

Diagnosis of GDM

Women at high risk for GDM should undergo glucose testing as soon as possible. An FPG greater than or equal to 126 mg/dL; or a casual plasma glucose greater than or equal to 200 mg/dL; or a A1C greater or equal to 6.5% meets the threshold for diagnosis of diabetes mellitus and should be confirmed on a subsequent day as soon as possible. Women of average or low risk, including those not found to have diabetes early in pregnancy, should undergo GDM testing at 24 to 28 weeks of gestation using a 50-g OGTT. This screen- ing test consists of 50 g of glucose given without regard to the last meal, followed in 1 hour by a venous blood sample for glucose concentration. If the plasma glucose level is greater than 140 mg/dL (7.8 mmol/L), a 100-g 3-hour OGTT is indicated to establish the diagnosis of GDM. If the plasma glucose measured 3 hours after the test is greater or equal to 140 mg/dL (7.8 mmol/L), a diagnosis of GDM is made.

Epinephrine

a catecholamine, helps to maintain blood glucose levels during periods of stress. Epinephrine has the potent effect of stimulating glyco- genolysis in the liver, thus causing large quantities of glucose to be released into the blood. It also inhibits insulin release from the beta cells and thereby decreases the movement of glucose into muscle cells, while at the same time increasing the breakdown of muscle glycogen stores. Although the glucose that is released from muscle glycogen cannot be released into the blood, the mobi- lization of these stores for muscle use conserves blood glucose for use by other tissues such as the brain and nervous system. Epinephrine also has a direct lipolytic effect on adipose cells, thereby increasing the mobiliza- tion of fatty acids for use as an energy source. The blood glucose-elevating effect of epinephrine is an important homeostatic mechanism during periods of hypoglycemia.

Glucagon functions

a polypeptide molecule produced by the alpha cells of the islets of Langerhans, helps to maintain blood glucose between meals and during periods of fasting. Like insulin, glucagon travels through the portal vein to the liver, where it exerts its main action, which is to increase blood glucose. The most dramatic effect of glucagon is its ability to initiate glycogenolysis (the breakdown of glycogen) as a means of raising blood glucose, usually within a matter of minutes. Glucagon also increases the transport of amino acids into the liver and stimulates their conversion into glucose through the process of gluconeogenesis. Other actions of glucagon occur only when the hormone is present in high concentrations, usually well above those normally present in the blood. At high concentrations, glucagon activates adipose cell lipase, making fatty acids available for use as energy.

Amylin

a polypeptide that is cosecreted with insulin from the beta cells in the pancreas. a hormone synthesized by pancreatic B cells that contributes to glucose control during the post-prandial period. slows glucose absorption in small intestine; suppresses glucagon secretion

diabetic peripheral neuropathies

a simplified system divides them into the somatic and autonomic nervous system neuropathies

Diabetic nephropathy

a term used to describe the combination of lesions that occur concurrently in the diabetic kidney, is the leading cause of chronic kidney disease (CKD) in persons starting renal replacement therapy. risk factors are genetic and familial predisposition, elevated blood pressure, poor glycemic control, smoking, hyperlipidemia, and increased albumin excretion. Diabetic nephropathy occurs in family clusters, suggesting a familial predisposition, although this does not exclude the possibility of environmental factors shared by siblings. The risk for development of kidney disease is greater among Native Americans, Hispanic Americans (especially Mexican Americans), and African Americans.

Prediabetes is associated with all of the following except: a. Increased risk of developing type 2 diabetes b. Impaired glucose tolerance c. Increased risk of heart disease and stroke d. Increased risk of developing type 1 diabetes

ans D

normal fasting blood glucose levels

are tightly regulated between 70 and 99 mg/dL (4.0 and 5.5 mmol/L).

Glucagon secretion is regulated by

blood glucose. A decrease in blood glucose concentration produces an immediate increase in glucagon secretion, and an increase produces a decrease in glucagon secretion. High concentrations of amino acids, as occur after a protein meal, also can stimulate glucagon secretion. In this way, glucagon increases the conversion of amino acids to glucose as a means of maintaining the body's glucose levels. Glucagon levels also increase during strenuous exercise as a means of preventing a decrease in blood glucose.

C-peptide levels

can be measured clinically, and this measurement can be used to study beta cell function (i.e., persons with type 2 diabetes with very little or no remaining beta cell function will have very low or nonexistent levels of C-peptide in their blood, and thus will likely need insu- lin replacement for treatment).

Type 1 diabetes mellitus

characterized by destruction of the pancreatic beta cells and accounts for 5% to 10% of those with diabetes, is subdivided into type 1A immune-mediated diabetes and type 1B idiopathic (non-immune-related) diabetes. In the United States and Europe, approximately 90% to 95% of people with type 1 diabetes mellitus have type 1A immune- mediated diabetes. Type 1 diabetes is subdivided into two types: type 1A, immune-mediated diabetes, and type 1B, idiopathic diabetes. Type 1A diabetes is characterized by autoimmune destruction of beta cells. Beta cell destruction in the absence of an autoimmune reaction is associated with type 1b diabetes, while autoimmune processes contribute to type 1a diabetes. They have increased predisposition to other autoimmune disorders such as Graves disease, rheumatoid arthritis, and Addison disease.

three major acute complications of impaired blood glucose regulation

diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), and hypogly- cemia. All are life-threatening conditions that demand immediate recognition and treatment.

Treatment of GDM

diet 1st, if that fails, then insulin If dietary management alone does not achieve a capillary blood glucose of 90 to 99 mg/dL or a 2-hour postprandial blood glucose less than 120 mg/dL, the Fifth International Workshop on GDM recommends therapy with insulin. More recently, several oral agents have also been used for the treatment of GDM, including glyburide and metformin. Self-monitoring of blood glucose levels is essential

diabetic retinopathy

disease of the retina in diabetics characterized by capillary leakage, bleeding, and new vessel formation (neovascularization) leading to scarring and loss of vision. Diabetic retinopathy is characterized by abnormal retinal vascular permeability, microaneurysm forma- tion, neovascularization and associated retinal hemorrhages, scarring, diabetic macular edema, and retinal detachment. In conjunction with the retinopathy, the inflammatory response causes macular edema. risk factors associated with diabetic retinopathy are poor glycemic control, elevated blood pressure, dyslipidemia, and smoking.

Macrovascular complications of diabetes

disorders that affect large blood vessels, including the coronary arteries and arteries of the limbs

Diagnosis of GDM

end of the second trimester between 24 and 28 weeks' gestation in women with low risk for GDM. Patients with one or more risk factors should be screened at their first prenatal visit and, if negative, again in the early third trimester. true gestational diabetics, fasting values are commonly normal while postprandial values are elevated. This is because the pathophysiology is related to metabolism of large carbohydrate boluses rather than carbohydrate intolerance at baseline.

Signs and symptoms of hyperglycemia

excessive food intake, thirst, gradual onset insufficient insulin dosage, warm, dry skin infection, vomiting, Kussmaul respirations sweet breath, restlessness, abnormal or slurred speech, unsteady gait, recurrent blurred vision, fatigue, paresthesias, and skin infections. Pruritus and vulvovaginitis due to Candida infections are com- mon initial complaints in women with diabetes. Balanitis secondary to Candida infections can occur in men.

ketoacidosis

excessive production of ketones, making the blood acid. During fat breakdown, liver converts fatty acids into ketones and releases them into the blood. Because ketones are organic acids, release of excessive amounts can occur in DM. In situations that favor fat breakdown, such as fasting, large amounts of ketones are released into the bloodstream. Because ketones are organic acids, release of excessive amounts, as can occur in diabetes mellitus.

When the liver and skeletal muscles become saturated with glycogen, any excess glucose is converted into

fatty acids by the liver and then stored as triglycerides in the fat cells of adipose tissue.

other causes of hyperglycemia in diabetics

genetic defects of beta cells function Genetic defects in insulin action trauma to pancreas endocrine disorders - acromegaly, pheochromocytoma, hyperthyroidism, cushing syndrome medications: steroids, thyroid hormone infections treatments like TPN gestation Stressful events such as surgery: causes the release of cortisol (Elevation of glucocorticoid levels) which leads to inordinately elevated blood glucose levels. Drug or chemical-induced conditions (pentamidine, nicotinic acid, glucocorticoids, thyroid hormone,diazoxide, thiazides, phenytoin, interferon-alpha, other drugs)

counterregulatory hormones

glucagon cortisol epinephrine (a catecholamine) norepinephrine growth hormone have the opposite effects of insulin on skeletal muscle, adipose tissue, & the liver. the catecholamines, growth hormone, and the gluco- corticoids. These hormones, along with glucagon, are sometimes called counterregulatory hormones because they counteract the storage functions of insulin in reg- ulating blood glucose levels during periods of fasting, exercise, and other situations that either limit glucose intake or deplete glucose stores

Gestational diabetes mellitus (GDM)

glucose intolerance that develops during pregnancy and is not clearly overt diabetes (either type 1 or type 2). high-risk ethnic/racial group (e.g., H Hispanic, Native American, Asian, African American)

incretin effect

gut-derived hormones that increase insulin release after an oral nutrient load. This suggests that gut- derived factors can stimulate insulin secretion after a predominantly carbohydrate meal. The two hormones that account for about 90% of the incretin effect are glucagon-like peptide-1, which is released from L cells in the distal small intestine, and glucose-dependent insulinotropic polypeptide, which is released by K cells more proximally (mainly in the jejunum)

growth hormone

hormone secreted by anterior pituitary gland that stimulates growth of bones.

Hypoglycemia symptoms

hunger, fatigue, weakness, sweating, headache, dizziness, low bp, cold or clammy skin The signs and symptoms of hypoglycemia can be divided into two categories: (1) those caused by altered cerebral function and (2) those related to activation of the autonomic nervous system. Because the brain relies on blood glucose as its main energy source, hypoglycemia produces behaviors related to altered cerebral function. Headache, dif culty in prob- lem solving, disturbed or altered behavior, coma, and seizures may occur. At the onset of the hypoglycemic episode, activation of the parasympathetic nervous sys- tem often causes hunger. The initial parasympathetic response is followed by activation of the sympathetic nervous system; which causes anxiety, tachycardia, sweating, and a cool and clammy skin due to constric- tion of the skin vessels.

risk associated with exercise in diabetics

hypoglycemia Should Carry a snack with carbs to prevent profound hypoglycemia. People with diabetes are usually aware that delayed hypoglycemia can occur after exercise. Although muscle uptake of glucose increases significantly, the ability to maintain blood glucose levels is hampered by failure to suppress the absorption of injected insulin and activate the counterregulatory mechanisms that maintain blood glucose (to cause a hyperglycemia response). Even after exercise ceases, insulin's lowering effect on blood glucose levels continues, resulting in profound symptomatic hypoglycemia.

Somogyi effect

hypoglycemia followed by "rebound" hyperglycemia due to over response of counterregulatory hormones "hypoglycemia begets hyperglycemia." In people with diabetes, insulin-induced hypoglycemia produces a compensatory increase in blood levels of catecholamines, glucagon, cortisol, and growth hormone. These counterregulatory hormones cause blood glucose to become elevated and produce some degree of insulin resistance. The Somogyi effect describes a cycle of insulin-induced posthypoglycemic episodes. The cycle begins when the increase in blood glucose and insulin resistance is treated with larger insulin doses. The insulin-induced hypoglycemia produces a compensatory increase in blood levels of catecholamines, glucagon, cortisol, and growth hormone, leading to increased blood glucose with some insulin resistance. hypoglycemic episode often occurs during the night or at a time when it is not recognized, rendering the diagnosis of the phenomenon more difficult. Research suggests that even mild insulin-associated hypoglycemia, which may be asymptomatic, can cause hyperglycemia in people with type 1 diabetes through the recruitment of counterregulatory mechanisms, although the insulin action does not wane. A waning of insulin's effects when it occurs (i.e., end of the duration of action) causes an exacerbation of the post hypoglycemic hyperglycemia that occurs and accelerates its development. These findings may explain the labile nature of the disease in some people with diabetes. Measures to prevent hypoglycemia and the subsequent activation of counterregulatory mechanisms include a redistribution of dietary carbohydrates and an alteration in insulin dose or time of administration.

incretin effect

increased insulin secretion in response to an oral glucose load, in diabetes, this effect is blunted.

antidiabetic (non-insulin) agents used in the treatment of type 2 diabetes

insulin secretagogues, biguanides, α-glucosidase inhibitors, thiazolidinediones, SGLT2 inhibitors, and incretin-based agents

painful diabetic neuropathy

involves the somatosensory neurons that carry pain impulses. This disorder, which causes hypersensitivity to light touch and occasionally severe " burning pain," particularly at night, can become physically and emotionally disabling.

insulin

is the only hormone known to have a direct effect in lowering blood glucose levels. The actions are threefold: (1) it promotes glucose uptake by target cells and provides for glucose storage as glycogen, (2) it prevents fat and glycogen breakdown, and (3) it inhibits gluconeogenesis and increases protein synthesis. acts to promote fat storage by increasing the transport of glucose into fat cells; facilitates triglyceride synthesis from glucose in fat cells and inhibits the intracellular breakdown of stored triglycerides. also inhibits protein breakdown and increases protein synthesis by increasing the active transport of amino acids into body cells, and it inhibits gluconeogenesis, or the building of glucose from new sources, mainly amino acids. A protein hormone synthesized in the pancreas that regulates blood sugar levels by facilitating the uptake of glucose into tissues.

all people with type 1A diabetes require exogenous insulin replacement to reverse the catabolic state, control blood glucose levels, and prevent

ketosis

Glycosylated hemoglobin (i.e., HbA1c [A1C])

marker for chronic hyperglycemia, reflecting average blood glucose levels over a 2- to 3-month period of time. diagnosis of diabetes, with a threshold of greater than 6.5% .

biguanides

metformin (Glucophage) suppresses hepatic glucose production and increases the sensitivity of peripheral tissues to the actions of insulin. Metformin, the only currently available biguanide, inhibits hepatic glucose production and increases the sensitivity of peripheral tissues to the actions of insulin. Secondary benefits of metformin therapy include weight loss and improved lipid profiles. This medication does not stimulate insulin secretion; therefore, it does not produce hypoglycemia. However, it confers an increased risk for lactic acidosis, and is contraindicated in people with elevated serum creatinine levels, clinical and laboratory evidence of severe liver disease, or conditions associated with hypoxemia or dehydration.

hypoglycemia treatment

most effective treatment of an insulin reaction is the immediate administration of 15 g of glucose in a concentrated carbohydrate source. According to the so-called rule of 15, this 15 g of glucose can be repeated every 15 minutes for up to 3 doses. Monosaccharides such as glucose, which can be absorbed directly into the bloodstream, work best. Complex carbohydrates can be administered after the acute reaction has been controlled to sustain blood glucose levels. It is important not to over treat hypoglycemia and cause rebound hyperglycemia. Alternative methods for increasing blood glucose may be required when the person having the reaction is unconscious or unable to swallow. Glucagon may be given intramuscularly or subcutaneously. Glucagon acts by hepatic glycogenolysis to raise blood glucose. Because the liver contains only a limited amount of glycogen (approximately 75 g), glucagon is ineffective in people whose glycogen stores have been depleted. In situations of severe or life-threatening hypoglycemia, it may be necessary to administer glucose (20 to 50 mL of a 50% solution) intravenously. If hypoglycemia occurs with α-glucosidase inhibitors, it should be treated with glucose (dextrose) and not sucrose (table sugar), whose breakdown may be blocked by the action of the α-glucosidase inhibitors.

Hypoglycemia (insulin reaction) causes

not enough food, too much medication, too much exercise, not eating at the right time. The treatment of HHS requires judicious medical observation and care as water moves back into brain cells, posing a threat of cerebral edema. Extensive potas- sium losses that also have occurred during the diuretic phase of the disorder require correction. Because of the problems encountered in the treatment and the serious nature of the disease conditions that cause HHS, the prognosis for this disorder is less favorable than that for ketoacidosis.

2 primary acquired factors that predispose to type 2 diabetes

obesity and physical inactivity Other acquired factors include the patient's microbiome (i.e., the bacteria that live in or on us) related metabolic factors and inflammatory effects.

thiazolidinediones

pioglitazone (Actos), rosiglitazone (Avandia): sensitizes body tissue to insulin. (TZDs) or glitazones (e.g., pioglitazone, rosiglitazone) are the only class of drugs that directly target insulin resistance. They do this by increasing insulin sensitivity in the insulin-responsive tissues—liver, skeletal muscle, and fat—allowing the tissues to respond to endoge- nous insulin more efficiently without increased output from already dysfunctional beta cells. Because of the previous problem with liver toxicity in this class of drugs, liver enzymes should be monitored before start- ing therapy according to guidelines. Both agents can cause fluid accumulation and are therefore contraindi- cated in patients with stage III and IV heart failure. Other potential adverse effects include an increased risk of bone fractures and of bladder cancer.

HHS s/s

polyuria w/ adequate fluid intake hypotension severe dehydration tachycardia altered awareness seizures blood glucose over 800mg/dL hemiparesis extreme hyperglycemia; hyperosmolarity w/ dehydration; NO ketoacidosis; CNS dysfunction

A1C test

provides an index of blood glucose levels over the previous 6 to 12 weeks. Glycosylated hemoglobin is hemoglobin into which glucose has been irreversibly incorporated. Because glucose entry into the red blood cell is not insulin dependent, the rate at which glucose becomes attached to the hemoglobin molecule depends on blood glucose; the level is an index of blood glucose levels over the previous 6 to 12 weeks.

Microvascular complications

retinopathy, neuropathy, nephropathy

Adiponectin

secreted by adipocytes and circulates in the blood, is the only known adipocyte-secreted factor that increases tissue sensitivity to insulin.23 It has been shown that decreased levels of adiponectin coincide with insulin resistance in persons with obesity and type 2 diabetes. In skeletal muscle, adiponectin has been shown to decrease tissue triglyceride content by increasing the use of fatty acids as a fuel source. Adiponectin also appears to have antidiabetes, anti-in ammatory, and antiatherogenic effects.

Somatostatin

secreted by the delta cells acts locally in the islets of Langerhans to inhibit the release of insulin and glucagon. It also decreases gastrointes- tinal activity after ingestion of food. Almost all fac- tors related to ingestion of food stimulate somatostatin secretion. By decreasing gastrointestinal activity, soma- tostatin is thought to extend the time during which food is absorbed into the blood, and by inhibiting insulin and glucagon, it is thought to extend the use of absorbed nutrients by the tissues.

Somatostatin

suppresses secretion of glucagon and insulin. hormone that inhibits release of growth hormone and insulin

multiple daily injections (MDIs)

the basal insulin requirements are met by an intermediate- or long- acting insulin administered once or twice daily. Boluses of rapid- or short-acting insulin are used before meals.

Almost all body cells, use fatty acids interchangeably with glucose for energy. Exception is:

the brain, nervous tissue, and red blood cells, which can only use glucose for energy.

Glycogenolysis

the breakdown of glycogen into glucose by the liver, releasing it back into the circulating blood in response to a very low blood sugar level

the primary determinant of elevated FPG in persons with type 2 diabetes

the excessive rate of hepatic glucose production

fasting plasma glucose (FPG) test

which measures plasma glucose levels after food has been withheld for at least 8 hours, A FGP below 100 mg/dL is considered normal

an oral glucose tolerance test (OGTT)

which measures the body's ability to remove glucose from the blood within 2 hours of consuming 75 g of glucose in 300 mL of water. an OGTT less than 140 mg/dL is considered normal