Ch41 Diabetes Mellitus

pancreas by the β cells of the islets of Langerhans

proinsulin

glucagon

somatostatin

pancreatic polypeptide

• ingestion of nutrients stimulates release of glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) from cells in the gut;
• these stimulate the production of insulin and inhibit glucagon
• insulin stimulates diffusion of glucose into adipose and muscle tissue 
• glucose oxidized in the cell (glycolysis) and used primarily for glycogenesis

• glucose produced by glycogenolysis and gluconeogenesis while insulin secretion falls to basal level 
• glucagon responsible for glucose production in fasting state 
• other counterregulatory hormones help (ex: corticosteroids, GH, catechlamines)

glucagon

• initially insulin drops and glucagon and catecholamine rise; increasing production of FFAs and stimulating glycogenolysis 
• rise in glucose to meet energy demands 
• muscle tissue increases metabolism of glucose as exercise cont; increasing insulin sensitivity and maintaining normal blood glucose levels in presence of lower insulin levels

• stress hormones (corticosteroids and catecholamines) increase production of glucose in liver and glucagon in pancreas, & decrease use of glucose 
• catecholamines increase production of FFAs and inhibits glucose uptake in periphery 
• all this leads to hyperglycemia

characterized by destruction of B cells of pancreas

etiology may be immune-mediated or idiopathic

diagnosed between 5-20 yrs of age

• absolute insulin deficieny 
• overproduction of glucagon stimulates glycogenolysis and gluconeogenesis
• glucose lvl rise, leads to polyuria, polydipsia, and polyphagia 
• FFAs are turned into ketones --> ketoacidosis

• most common form;
• non-caucasian and elderly
• insulin resistance and B cell dysfunction lead to a relative lack of insulin

common factors: obesity, aging, and sedentary lifestyle

• polyuria, polydipsia, polyphagia - subtle 
• ketoacidosis is uncommon 
• HHNK - hyperglycemic hypersmolar nonketotic coma can develop due to severe dehydration (more common in older adults)

• onset during pregnancy
• precipitated by the presence of placental hormones 
• manage thru dietary counseling, exercise, and blood glucose/ketone monitoring

impaired glucose tolerance and impaired fasting glucose tolerance

by alterations in nutrition, inactivity, or inadequate use of antidiabetic meds

prone to infections

polyuria, polydipsia, polyphagia, nausea, fatigue, blurred vision

• systemic changes over time and increase the risk of other diseases, including metabolic syndrome, hypertension, cardiovascular disease, and stroke 
• complications: vascular and neuropathic

Macrovascular: damage to large blood vessels; leads to CVD and stroke 

Microvascular: retinopathy and nephropathy fr. abnormal thickening of basement membrane in capillaries; may lead to blindness and renal failure

MD - independent risk factor for CAD (coronary artery disease)

• hyperglycemia disrupts platelet function and growth of basement membrane 
• thickening of basement membrane may improve with glycemic control 
• risk factors: +hypertension and smoking

• GI disturbances
• bladder dysfunction, 
• tachycardia
• postural hypotension
• sexual dysfunction

• carpal tunnel syndrome, paresthesias
• or dysesthesias in extremities

• excessive glucose thought to interfere with myoinositol in neurons and reduced myoinositol in peripheral nerves 
• glycemic control may prevent/improve symptoms of diabetic neuropathy

• Type 1: higher risk of perinatal infant mortality and congenital abnormalities 
• glycemic control before and during reduce risks

• used to repair and growth of tissue 
• stimulates secretion of insulin w/o increasing plasma blood glucose 
• excessive protein may cause nephropathy

• sat, monounsaturated, unsat. 
• dietary saturated fat and cholesterol lead to ypercholesterolemia 
• limit sat fat to less than 7% of total intake and <200 mg of cholesterol daily

• categorized as monosaccharides and polysaccharides 
• monitored with carbohydrate counting 
• glycemic load and index may also be of benefit

• obesity: a body mass index (BMI) >30kg/m2
• bulimia and anorexia more common in type 1 DM

• lowers cardiovascular risk factors 
• may be beneficial toward wt reduction or maintenance 
• may lower meds requirements 
• Type 1 DM at risk of hypoglycemia and ketoacidosis

• Sulfonylureas
• biguanides

induce insulin release by B cells, augment the action of insulin in glucose disposal, diminish insulin clearance by liver, and reduce hepatic glucose production

suppress hepatic gluconegogenesis and enhance glucose uptake by peripheral tissues

• α-Glucosidase inhibitors
• Thiazolidinediones

diminish postprandial hyperglycemia by delaying carbohydrate absorption

increase tissue sensitivity to insulin and inhibit hepatic gluconeogenesis

inhibit enzymatic breakdown of the incretin hormones, GLP-1 and GIP

amylin-mimetic agents used in conjunction with insulin for the management of glycemia

Hypoglycemia

• glycosylated hemoglobin (glycemic control)
• vlues of less than 7%
• capillary glucose testing 
• test for glucosuria and ketones