OMFS Secrets, Ch21, MANAGEMENT OF THE DIABETIC PATIENT

What are the hallmark symptoms of diabetes?

*Polyuria* (excessive urination >3L/d adult, >2L/d child), *polydipsia* (excessive thirst), and *polyphagia* (excessive eating/hunger). Other symptoms may include fatigue, weight loss, blurred vision, fungal infections, and neuropathy of hands and feet.

What is DM2?

*• Type 2 diabetes* (noninsulin-dependent diabetes mellitus or NIDDM). Initially characterized by insulin resistance secondary to environmental and genetic factors, followed by failure of beta cells of the pancreas to compensate for the increased insulin requirements. It accounts for >90% of all cases of diabetes mellitus. It is usually a disease of adulthood; however, it is being increasingly diagnosed in younger age groups. Therefore their muscle and adipose cells cannot transport glucose.

What is a basal rate and a bolus?

A basal rate is a constant rate of insulin delivered over 24 hours, keeping blood glucose levels in range between meals and overnight. The rate of insulin can be programmed to deliver different amounts of insulin at different times of the day and night. A bolus amount of insulin is used to cover the carbohydrate in each meal or snack. There are buttons on the insulin pump that will deliver the bolus if the meal is larger than planned, and a larger bolus of insulin can be programmed to cover it.

How does sorbitol accumulation lead to diabetic complications?

Cells of the tissues that do not require insulin for glucose transport (see question 22) become hypertonic. In Schwann's cells, the hypertonicity causes loss of feeling in extremities and a decrease in sensation. In the lens of the eye, water accumulation leads to cataracts, macular edema, and glaucoma. Damage to endothelial cells leads to thickening of basement membranes, resulting in microangiopathies of the retina, arterioles of the kidneys, and small vessels of the skin.

How do advanced glycosylation end-products (AGEs) contribute to diabetic complications?

AGEs are the result of enzymatic glycosylation. They get incorporated into the collagen that comprises the basement membranes of capillaries located in the eye, kidney, nerves, and skin. This results in thickening of basement membranes and a reduction in production of relaxing factors by the endothelium, causing vasoconstriction and, ultimately, hypertension. In addition, AGEs irreversibly attach to collagen walls in larger vessels. This impedes the normal efflux of LDLs entering the vessel wall and promotes cholesterol deposition.

What are the contraindications to the use of metformin in type 2 diabetes?

ALCOHOLICS, RENAL INSUFFICIENCY, LIVER DZ Metformin therapy is strictly contraindicated in alcoholics, patients with significant renal insufficiency or failure (serum creatinine >1.5 and >1.4 for women), and patients with liver disease. These conditions considerably increase the risk of lactic acidosis, a fatal side effect. Patients who are older than age 70 and those with low cardiac ejection fractions also are not candidates for metformin therapy. Patients who are about to receive iodine contrast dye, such as before cardiac catheterization, or who are to undergo major surgery should discontinue metformin 48 to 72 hours before the procedure.

What metabolic abnormalities are associated with type 1 diabetes?

Abnormalities are classified into those of carbohydrate, protein, and lipid metabolism. • Type 1 patients generally have a combination of glucose underutilization and excessive glucose production resembling the fasting state. Glucose is unable to get into certain tissues, which causes the renal threshold to be surpassed, resulting in polyuria. Polyuria leads to dehydration, which triggers polydipsia. In addition, because cells are not getting nourishment, patients experience polyphagia. • These patients break down protein from muscle to make glucose. Proteins are required for antibody production, white blood cell production, and healing of wounds. Deficiency of these proteins leads to susceptibility of infections and poor wound healing. • Insulin deficiency leads to lipolysis of triglycerides into free fatty acids. Excessive fatty acid breakdown leads to beta oxidation in the liver, creating acidic ketone bodies (acetoacetic acid and beta-hydroxybutyric acid). Ketone bodies enter the blood and cause a type of metabolic acidosis.

What is the enzyme that is responsible for the breakdown of glucose into sorbitol?

Aldose reductase.

What is the response of insulin and glucagon to dietary protein?

An increase in both hormones.

What is the management of a patient with insulin-controlled diabetes who is undergoing major surgery?

Basal insulin is required at all times. Most diabetic patients who receive insulin use a combination of intermediate-acting (NPH) and regular insulin. The formulation is 70% NPH and 30% regular insulin.. In these patients, total insulin dosage is usually given in the morning or divided between morning and afternoon. Typically two-thirds of the NPH and regular insulin formulation is given in the morning and one-third is given in the afternoon.

What are normal blood glucose values?

Blood glucose levels are normally maintained between *60 and 130 mg/dL.*

What are some of the ocular problems manifested in diabetic patients?

Cataracts, retinopathy, and glaucoma. Diabetic retinopathy is the leading cause of blindness in the United States.

What are the different categories of hypoglycemia?

Categories of hypoglycemia can be broken down depending on the level of plasma glucose and associated signs and symptoms (Table 21-1).

What is the oral combination drug Metaglip?

Combination: Biguanide + sulfonylurea (glipizide + metformin) Indications: (1) Initial management of DM2 when hyperglycemia poorly controlled w/ diet/exercise, or; (2) second-line tx when neither sulfonylurea+metformin effective alone. Dosages are expressed as glipizide/metformin components. When used as initial therapy, 1.25 mg/250 mg is taken daily or twice daily with meals. As second-line therapy,2.5 mg/500 mg or 5 mg/500 mg is given twice daily with meals.

What is the oral combination drug Glucovance?

Combination: Biguanide and sulfonylurea (glyburide) Indication: Initial managment of DM2 or 2nd line therapy when sulfonylurea / metformin is ineffective alone. Glucovance dosages are expressed as glyburide/metformin components. When used as initial therapy, 1.25 mg/250 mg is taken with a meal once daily. Patients with an HgA1c >9% or fasting plasma glucose >200 mg/dL are started at 1.25 mg/250 mg twice daily. The maximum dose is not to exceed 10 mg/2000 mg. For those patients previously treated with a sulfonylurea or metformin alone, the initial dose is 2.5 mg/500 mg or 5 mg/500 mg twice a day.

What is the oral combination drug Avandamet?

Combination: biguanide + thiazolidinediones, such as metformin and Avandia. Indication: Type 2 diabetics not adequately controlled w/ metformin alone. The dosage is determined by starting Avandia 4 mg/day and adding it to the current metformin dose. If the patient is already taking Avandia, then add metformin so that the patient is getting l000 mg/day.

How is cortisol secreted and regulated?

Cortisol is a glucocorticoid released in response to stress and low blood glucose. The control pathway for cortisol secretion is known as the hypothalamic-pituitary-adrenal (HPA) pathway. Corticotropinreleasing hormone (CRH) is released from the hypothalamus. CRH stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH stimulates cortisol release from the zona fasciculata of the adrenal cortex, which in turn causes negative feedback to CRH and ACTH.

What is diabetes?

Diabetes is a chronic metabolic disorder resulting in hyperglycemia from defects in insulin secretion, insulin action, or both. Diabetes creates a physiologic predisposition for developing generalized microvascular, macrovascular, and neuropathic complications.

What is diabetic ketoacidosis?

Diabetic ketoacidosis (DKA) is an acute, life-threatening medical emergency that can occur in type 1 and type 2 diabetic patients (more commonly in type 1). DKA is the result of severe insulin deficiency coupled with an absolute or relative increase of glucagon, which contribute to accelerated ketogenesis and severe hyperglycemia. Diagnostic criteria of DKA include blood glucose levels >450 mg/dL, metabolic acidosis (pH <7.3), serum bicarbonate <15 mEq/L, ketonemia, and ketonuria. Clinical manifestations include nausea and vomiting, Kussmaul respirations (rapid, deep breathing) to reduce carbon dioxide levels in blood, abdominal pain, fruity acetone breath odor, altered mental status/coma, dehydration, and tachycardia. Goals of treatment are fluid replacement initially using 0.9% normal saline intravenously (add 5% glucose once blood glucose reaches 250 mg/dL to prevent hypoglycemia) and administration of insulin after confirming patient is not hypokalemic (0.1 u/kg of regular insulin followed by infusion of 0.1 units/kg/hr); monitor and replace potassium, magnesium, and phosphate within 1 to 2 hours of starting insulin. Bicarbonate replacement is controversial and not necessary in most cases. Complications of treatment of DKA include cerebral edema if glucose levels decease too rapidly, hyperchloremic non-gap metabolic acidosis due to rapid infusion of normal saline, cardiac arrhythmias, and death.

What are the most common types of infections in diabetics and why?

Diabetic patients have enhanced susceptibility to infections of the skin, tuberculosis, pneumonia, and pyelonephritis. Together, these infections cause the death of about 5% of diabetics. In addition, diabetics are very susceptible to fungal infections. The susceptibility to infections is a combination of impaired leukocyte function, inability to make antibodies against the bacteria, and vascular insufficiency.

What happens during energy deprivation?

During energy deprivation states, triglycerides (omega-3 fatty acids attached to glycerol) are broken down into glycerol and fatty acids (lipolysis), which are converted to glucose. Amino acids can be converted to glucose in the liver through gluconeogenesis.

How does epinephrine exert its metabolic controls?

Effects are mediated through both alpha-1 and beta-2 receptors. Alpha-1 receptors of the pancreas promote glucagon release from the alpha cells of the pancreas and inhibit insulin secretion at the beta cells of the pancreas. Beta-2 receptor agonism results in lipolysis, gluconeogenesis, and glycogenolysis.

How will epinephrine that is released from the adrenal medulla affect plasma glucose?

Epinephrine decreases glycogen synthesis in the liver. In addition, its release is increased in response to hypoglycemia.

Which hormones are considered ketogenic? Why?

Epinephrine, glucocorticoids, glucagon, and growth hormone because they promote lipolysis.

What is exenatide?

Exenatide (Byetta) is a glucagon-like peptide-1 agonist that mimics incretin and promotes insulin secretion, suppresses glucagon, and slows gastric emptying. It is an injectable drug approved by the FDA for the treatment of type 2 diabetics who have not been able to achieve their target HgA1c levels using metformin, a sulfonylurea, or a combination drug. As with pramlintide, exenatide is injected with meals, and patients using it have experienced improved HgA1c levels and modest weight loss.

Intermediate procedures and insulin?

For intermediate procedures (breakfast and lunch are delayed/missed): • Omit any short-acting insulin on the morning of surgery. • For patients who take two types of insulin (intermediate/long-acting and rapid/short-acting), only in the morning, give one-half to two-thirds of their usual total morning insulin dose (both types). • For patients who take insulin (intermediate/long-acting and rapid/short-acting) two or more times a day, give one-third to one-half of the total morning dose (both types of insulin). • Start dextrose containing intravenous solution to provide 3.75 to 6.25 g glucose/hour to avoid metabolic changes of starvation. • For patients who develop hyperglycemia, supplemental short-acting insulin may be administered subcutaneously. • During surgery, plasma glucose, serum electrolytes, and arterial blood gases (ABGs) should be monitored. • Once the patient has resumed oral intake, NPH insulin is started. The patient's plasma glucose is monitored, and the insulin dosage is adjusted with regular insulin as needed.

Short procedures and insulin?

For short procedures (<2 hours): If breakfast is delayed, patients may delay taking their usual short-acting insulin until after surgery and before eating. Those who take long-acting insulin may continue basal insulin without any change to the usual regimen.

How does glucagon (medication) work? what is it used for?

Glucagon binds glucagon receptor and a bunch of cool shit happens to produce glu-1-phosphate Treat low blood sugar, beta blocker overdose, calcium channel blocker overdose, and those with anaphylaxis who do not improve with epinephrine.[2] It is given by injection into a vein, muscle, or under the skin.[2]

From where is glucagon secreted?

Glucagon is secreted from alpha cells of the endocrine pancreas during the fasted state when blood glucose concentrations fall below 100 mg/dL or with increased sympathetic activity. It is also found in the alpha cells of the stomach.

How is glucose normally metabolized? What happens to excess glucose? Too much glucose vs not enough?

Glucose absorbed after meal enters circulation of *hepatic portal system* and is taken to the *liver* where about *30% of all ingested glucose is metabolized.* The remaining glucose continues in the bloodstream for distribution to other organs and tissues. Excess glucose is converted to glycogen (glycogenesis) stored mostly in liver and muscle and triglycerides stored in adipose tissue (lipogenesis). If plasma glucose concentrations decrease, the body breaks down glycogen to glucose (glycogenolysis).

How does glycosylation of platelets affect microvascular disease?

Glycosylation --> adhesive --> platelet produces thromboxane --> hypercoagulable --> predisposes a diabetic to microvascular disease.

What is the role of growth hormone in glucose regulation? where produced? stimuli for excretion? how does it's effects relate to insulin?

Growth hormone is an anabolic hormone secreted by cells in the anterior pituitary gland. It is secreted by stimuli such as exercise-induced hypoglycemia, fasting, and stress from trauma, fever, and surgery. Growth hormone counteracts, in general, the effects of insulin on glucose and lipid metabolism. Growth hormone release is inhibited by glucose and free fatty acids. Growth hormone also increases plasma glucose, mobilizes free fatty acids and protein stores, lipolysis, glycogenolysis, and inhibits glucose uptake by muscle and adipose tissue.

What is hyperosmolar hyperglycemic nonketotic coma?

Hyperosmolar hyperglycemic nonketotic coma (HHNS) is a state of severe hyperglycemia (>600mg/dL), hyperosmolarity (>320 mOsm/L) and dehydration. It usually occurs in patients who are type 2 diabetics, age 65 or older. It is less common than DKA, but it carries a higher mortality rate. Low insulin levels lead to hyperglycemia, causing osmotic diuresis and dehydration. Ketogenesis is minimal because a small amount of insulin is released to blunt counterregulatory hormone release (glucagon). Ketosis and acidosis are typically minimal or absent. The symptoms may go unrecognized for weeks. Key features of HHNS are severe hyperosmolarity (>320 mOsm/L), hyperglycemia (>600 mg/dL), dehydration, and the absence of acidosis and ketosis (unlike DKA). BUN is usually elevated with other laboratory findings consistent with prerenal azotemia. The treatment involves fluid replacement with normal saline (1 L in the first hour followed by another liter in the next 2 hours. Switch to 5% glucose in one-half normal saline once blood glucose reaches 250 mg/dL) and administration of insulin (initial bolus of 5 to 10 units intravenously, followed by a low-dose infusion of 2 to 4 units/hour). Complications include cerebral edema from rapid lowering of glucose, exacerbation of CHF in predisposed patients, cardiac arrhythmias, and death.

What is the pharmacology of the thiazolidinediones?

IMPROVE INSULIN RESPONSE IN FAT/MUSCLE At the same time, they DO NOT increase pancreatic secretion of insulin. The thiazolidinediones are taken once or twice a day with food. These drugs can be used by themselves or in combination with sulfonylureas, metformin, or insulin. However, thiazolidinediones can have a rare but serious effect on liver function requiring regular liver function tests. This could affect the length of time that the amide local anesthetics are in circulation.

For long and complex procedures (Insulin?)

IV insulin is usually required. Blood glucose and electrolytes should be closely monitored (no less than hourly). Generally, insulin infusions should be started early in the morning prior to surgery to allow time to achieve glycemic control. The most common infusion is the glucose insulin potassium (GIK) infusion. It contains 10% dextrose, 10 mmol of potassium chloride, and 15 units of short-acting insulin.

How do you treat severe hypoglycemia?

If a glucagon kit is available, the patient should be given a subcutaneous injection of glucagon. The adult dose is 1 mg; children younger than age 5 years, 0.5 mg; and infants younger than 1 year, 0.25 mg. If no kit is available and the patient can swallow without risk of aspiration, 15 to 50 g of a carbohydrate source can be given on the inside of the cheek. Sources include glucose gel, 1 to 4 tsp of honey (except in infants), syrup, or jelly. When the patient is more alert, follow with a liquid such as orange juice.

How do you manage a patient with diabetes that is controlled by diet only?

If plasma glucose levels exceed and remain above 250 mg/dL as a consequence of surgical stress or infection, sliding-scale short-acting insulin therapy should be instituted.

What is the pathogenesis of type 1 diabetes?

Overt signs of type 1 diabetes do not typically appear until about 90% of beta cells are destroyed. • A *genetic* susceptibility predisposes some people to autoimmunity against beta cells of the pancreas. • *Autoimmunity* develops spontaneously or, more commonly, is stimulated by an environmental agent. • *Environmental* injury can damage beta cells, which are then recognized as foreign by the immune defenses.

What is the pharmacology of the sulfonylureas?

Increase insulin secretion from the beta cells and potentiate insulin action on several extrahepatic tissues. Long-term sulfonylureas increase peripheral utilization of glucose, suppress hepatic gluconeogenesis, and possibly increase the sensitivity or number of peripheral insulin receptors. Primarily for type 2 diabetics

How do you treat mild to moderate hypoglycemia?

Initially, treat with 10 to 15 g of carbohydrates. Give the patient one-half cup of orange juice or a regular soft drink, three to five hard candies, one cup of milk, three glucose tablets, or two tbsp. of raisins. Evaluate plasma glucose levels as soon as possible. If symptoms do not improve in 15 minutes, treat with an additional 10 to 15 g of a carbohydrate source.

How does insulin facilitate uptake of glucose into cells? How soon after meal is insulin released? Insulin receptors?

Insulin is released in a rapid surge during the first *10 to 30 minutes after a meal.* This is followed by a second phase of a slower, sustained release of insulin. Insulin receptors in the cell membrane have *alpha and beta subunits.* Insulin binds to subunit alpha, which causes a change in subunit beta. Subunit beta promotes the activity of the enzyme tyrosine kinase that phosphorylates intracellular insulin receptors (insulin-receptor substrates). This activates second messenger pathways that alter existing protein and protein synthesis. The net result is a change in cell metabolism that brings glucose into the cell via GLUT transporters.

From where is insulin secreted?

Insulin is secreted from the beta cells of the endocrine pancreas during the fed state when blood glucose concentrations rise above 100 mg/dL or with increased parasympathetic activity.

How do insulin pumps work?

Insulin pumps deliver short-acting insulin 24 hours a day through a catheter placed subcutaneously. Doses: basal rates, boluses, and doses to correct glucose levels.

What is the response by insulin to parasympathetic stimulation?

Insulin release will be increased

What metabolic abnormalities are associated with type 2 diabetes?

Insulin resistance Loss of sensitivity of cells to insulin Decrease in insulin secretion. Insulin is unable to get into cells because either a post-receptor defect prevents uptake or there is a problem of insulin binding to target cells in the liver, muscle, and adipose tissue. In addition, type 2 diabetics may have a gradual decrease in basal levels of insulin secretion because the pancreas loses sensitivity to glucose level changes

What is pramlintide?

Its brand name is Symlin, and it is a synthetic form of the hormone amylin, which is produced in the beta cells of the pancreas. It slows gastric emptying, suppresses glucagon, and regulates appetite. It is an injectable drug that has been recently approved by the FDA. Pramlintide has been approved for type 1 diabetics who are not achieving their A1c goal levels, and for type 2 diabetics using insulin and unable to achieve their A1c goals. It has been shown to modestly improve HgA1c levels, as well as promote modest weight loss without causing increased hypoglycemia.

What considerations should be taken in diabetic patients who require contrast imaging?

Patients with diabetes are susceptible to developing radiocontrast-induced acute renal failure. If IV contrast is necessary, give generous hydration before administering contrast agent. If the patient is on metformin, hold it for 48 hours after contrast is given to prevent renal damage. Make sure renal function has returned to baseline before resuming it.

Which oral hypoglycemic is categorized as a biguanide?

Metformin (Glucophage) reduces hepatic glucose production, decreases GI glucose absorption, and increases target cell insulin sensitivity.

What is the best route to administer agents to stimulate insulin release? Oral vs IV?

Oral glucose and amino acids have a greater stimulatory effect on insulin than intravenously administered solutions because of stimulation of intestinal hormones by ingested substances. These hormones include gastric inhibitory peptide, cholecystokinin (CCK), glucagon, and gastrin. All are stimulators of insulin secretion.

What metabolic role does cortisol play in glucose metabolism?

Overall cortisol is catabolic and prevents hypoglycemia. It promotes gluconeogenesis in the liver, breakdown of skeletal muscle proteins into pyruvate and lactate, which facilitate gluconeogenesis, and enhances lipolysis. The glycerol from fatty acids can be used for gluconeogenesis.

What is the pharmacology of the meglitinides?

STIMULATE INSULIN RELEASE BEFORE MEALS ...by the beta cells of the pancreas to reduce postprandial hyperglycemia. These drugs are taken before each of three meals. Type 2 DM

How do you manage a surgical patient who controls diabetes with oral hypoglycemic agents?

Short-acting sulfonylureas and oral agents should be withheld on the operative day. Metformin and long-acting sulfonylureas (Chlorpropamide) should be held 1 day before planned surgical procedures. Metformin is typically held 48 hours postoperatively. Renal function should be normal prior to resuming treatment. Glucose values should be checked regularly postoperatively, and elevated levels >180 mg/dL may be treated with short-acting sliding-scale insulin.

What are the effects of surgery on glucose control?

Surgery/GA --> STRESS RESPONSE --> Release of epinephrine, glucagon, cortisol, growth hormone, interleukin-6, and tumor necrosis factor alpha. This results in INSULIN RESISTANCE, decreased peripheral glucose utilization, impaired insulin secretion, increased lipolysis, and protein catabolism. These effects can lead to HYPERGLYCEMIA and KETOSIS in some cases.

Where is the major site of action for glucagon?

The breakdown of hepatic glycogen to glucose

What is the importance of nonenzymatic glycosylation of hemoglobin?

The degree of nonenzymatic glycosylation is dependent on the amount of plasma glucose levels. Therefore high levels result in more glycosylation of hemoglobin. The normal hemoglobin A1c is 4% to 6%. In diabetics, levels may reach 16% to 20%. Because the lifespan of a red blood cell is about 120 days and the glycosylation occurs continuously over that span, hemoglobin A1c concentrations provide an index of the average blood glucose over the preceding 60 to 90 days.

What are the criteria for the diagnosis of diabetes mellitus?

The diagnosis is made based on one or more of the following criteria (perform tests on two separate days): • Signs and symptoms plus a random plasma glucose concentration ≥200 mg/dL • A fasting plasma glucose ≥126 mg/dL on two occasions • Oral glucose tolerance test with a 2-hour postprandial glucose concentration ≥200 mg/dL and a time 0 serum glucose level >126 mg/dL; hemoglobin A1c >6.5

What test is accepted by the American Diabetes Association for diagnosing diabetes?

The fasting plasma glucose test is a diagnostic marker for diabetes. The patient fasts overnight for at least 8 hours, and the test is performed the next morning. This test is performed only on non-pregnant adults who are not taking any medications and do not have any other metabolic conditions that would lead to abnormal results. A normal fasting plasma glucose is usually 65 to 110 mg/dL.

What metabolic effects does glucagon regulate?

The metabolic effects exerted on the liver, muscle, and adipose tissue are antagonistic to those of insulin. Glucagon mobilizes stored energy by promoting glycogenolysis (especially at the liver), gluconeogenesis, and lipolysis by activating hormone-sensitive lipase. Other effects of glucagon include stimulating the secretion of insulin by increasing plasma glucose and stimulating the secretion of growth hormone.

What is the role of epinephrine in glucose regulation?

The overall goal of epinephrine is to protect plasma glucose levels. In the muscle and liver, it promotes glycogenolysis and gluconeogenesis as well. Additionally, it will inhibit insulin release and stimulate glucagon release through alpha-1 receptors in the pancreas. In the bloodstream, it will inhibit glucose uptake. Finally, epinephrine stimulates hormone-sensitive lipase to facilitate lipolysis in muscle and adipose tissue.

What biochemical pathways are suspected of contributing to diabetic complications?

The suspected pathways are enzymatic glycosylation and the buildup of sorbitol. Enzymatic glycosylation is the process by which glucose attaches to proteins throughout the body at a rate proportional to the plasma glucose concentration. The proteins glycosylated include serum albumin, collagen, basic myelin protein, and low-density lipoproteins (LDLs). The function of the proteins is altered. Hyperglycemia leads to buildup of glucose in tissues that do not require insulin for uptake. Excess glucose is metabolized to sorbitol, which creates an osmotic gradient favoring water diffusing into the cell.

What are the four different types of diabetes mellitus?

Type 1Dm Type2Dm GestationalDm SecondaryDm

What is the pharmacology of the alpha-glucosidase inhibitors?

These type 2 diabetic agents help the body to lower blood glucose levels by competitively inhibiting pancreatic alpha-amylase and intestinal brush border alpha-glucoside, resulting in delayed breakdown of ingested complex carbohydrates, therefore slowing the absorption of glucose. These drugs should be taken with the first bite of a meal. The alpha-glucosidase inhibitors can be used alone or in combination with a sulfonylurea metformin or insulin.

What is the oral glucose tolerance test, and how is it performed?

This test measures a person's ability to handle a glucose load over a period of time. The patient fasts overnight. In the morning, the fasting blood glucose is determined. The patient then ingests a 75-g glucose load. In children and non-pregnant adults, the blood glucose is tested every 30 minutes for 2 hours. The test is considered normal if the fasting blood glucose is <110 mg/dL and the 2-hour postprandial blood glucose is <140 mg/dL.

What is the role of thyroid hormone in glucose regulation?

Triiodothyronine (T3), which is the metabolically active form of thyroid hormone, and thyroxine (T4), which is the prohormone, both act to raise blood glucose. They do so by enhancing glycogenolysis and by enhancing protein metabolism and absorption of glucose from the intestines.

What are the differences between type 1 and type 2 diabetes?

Type1: sudden onset, any age (usually young), body habitus thin, ketosis, autoantibodies, low insulin Type2: gradual onset, adults, obese, ketosis rare, absent Ab, insulin high, nml, or low

What is the pathogenesis of type 2 diabetes? what is greatest risk factor? what happens to insulin production as we age?

• *Obesity is the greatest risk factor*. It does not cause diabetes but can unmask it. It is associated with increased plasma levels of free fatty acids, which make muscles more insulin resistant, causing decreased glucose uptake. • Insulin production decreases with age. • Genetics plays a significant but poorly understood role. • Lack of compensation in type 2 diabetics from failure of free fatty acids to stimulate pancreatic insulin secretion. Therefore, compensation does not occur, and hyperglycemia develops. Beta cells become desensitized to glucose, leading to decreased insulin secretion.

What is gestational DM?

• Gestational diabetes. Complicates up to 4% of all pregnancies. It typically resolves after delivery; however, up to 40% of women with gestational diabetes will develop type 2 diabetes within 10 years of developing gestational diabetes.

What hormones antagonize the action of insulin on blood sugar?

• Growth hormone • Glucagon • Cortisol • Epinephrine

How does insulin lower the plasma glucose?

• Insulin promotes glucose uptake into most tissues. Target tissues for insulin are the liver, adipose tissue, and skeletal muscles. Other tissues, including the brain and transporting epithelia of the kidney and intestine, do not require insulin for glucose uptake and metabolism. • Insulin enhances cellular utilization (glycolysis), storage of glucose (glycogenesis), and fat synthesis (lipogenesis). Insulin simultaneously inhibits glycogen breakdown (glycogenolysis), glucose synthesis in the liver (gluconeogenesis), and fat breakdown (lipolysis). • Insulin enhances utilization of amino acids in protein synthesis and inhibits protein breakdown. • Insulin promotes fat synthesis by inhibiting beta oxidation of fatty acids and promoting conversion into triglycerides (lipogenesis).

What tissues do not require insulin for glucose transport?

• Nervous tissue • Brain • Lens of the eye • Blood vessels • Kidney tubules

What are the major chronic complications of diabetes?

• Neuropathy (peripheral neuropathy [feet and hands], cranial nerve complications [most often involves CN III, IV, VI], mononeuropathies [median nerve, ulnar nerve, common peroneal], and autonomic neuropathy [impotence, neurogenic bladder, gastroparesis, constipation, postural hypotension]) • Retinopathy (nonproliferative retinopathy most common [funduscopic exam shows hemorrhages, exudates, microaneurysms, and venous dilation] and proliferative retinopathy [shows neovascularization and scarring, can lead to retinal detachment, vitreal hemorrhage, and blindness]) • Macroangiopathy (accelerated atherosclerosis, stroke, myocardial infarction, peripheral vascular disease) • Nephropathy (nodular glomerular sclerosis [Kimmelstiel-Wilson syndrome], diffuse glomerular sclerosis, isolated glomerular basement membrane thickening, microalbuminuria/proteinuria) • Increased susceptibility to infection (impaired WBC function, reduced blood supply, and neuropathy; increased risk of cellulitis, candidiasis, pneumonia, osteomyelitis, and polymicrobial foot ulcers)

What is secondary DM?

• Secondary diabetes. Diabetes that results from genetic defects in insulin secretion or action, exocrine pancreatic disease, pancreatectomy, endocrinopathies (e.g., Cushing's syndrome, acromegaly), drugs, and other syndromes.

What is DM1?

• Type 1 diabetes (insulin-dependent diabetes mellitus or IDDM). Characterized by a severe deficiency of insulin due to autoimmune destruction of beta cells of the pancreas. This form accounts for <10% of all cases of diabetes mellitus. It is usually associated with young people, but can occur at any age. These patients require insulin to maintain glucose homeostasis.