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Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CHAPTER 41DIABETES MELLITUS
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
REGULATION OF GLUCOSE METABOLISM
Hormonal Regulation• Insulin is synthesized in the pancreas by the β
cells of the islets of Langerhans• β cells produce proinsulin• α cells produce glucagon• δ cells produce somatostatin• F cells produce pancreatic polypeptide
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
REGULATION OF GLUCOSE METABOLISM (CONT.)
Hormonal Regulation• Ingestion of nutrients stimulates the 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
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
REGULATION OF GLUCOSE METABOLISM (CONT.)
Hormonal Regulation• In the fasting state, glucose is produced by
glycogenolysis and gluconeogenesis while insulin secretion falls to basal level
• Glucagon is responsible for most glucose production in fasting state
• Other counterregulatory hormones (corticosteroids, growth hormone, catecholamines) augment glucose production
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
REGULATION OF GLUCOSE METABOLISM (CONT.)
Exercise• Initially insulin levels drop and glucagon and
catecholamine levels rise, increasing production of free fatty acids (FFAs) and stimulating glycogenolysis
• Rise in glucose to meet energy demands• Muscle tissue increases metabolism of glucose as
exercise continues, increasing insulin sensitivity and maintaining normal blood glucose levels in the presence of lower insulin levels
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
REGULATION OF GLUCOSE METABOLISM (CONT.)
Stress• Production of stress hormones (corticosteroids
and catecholamines) increase production of glucose in the liver and glucagon in the pancreas, and decrease the utilization of glucose
• Catecholamines increase production of FFAs and inhibits glucose uptake in the periphery
• All of these events lead to hyperglycemia
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS
Classification of Glucose Intolerance Disorders• Type 1 diabetes mellitus• Type 2 diabetes mellitus• Other specific types of diabetes mellitus• Gestational diabetes mellitus
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Type 1 Diabetes Mellitus • Characterized by destruction of the β cells of the
pancreas• Usually diagnosed between 5 and 20 years of age• Etiology may be immune-mediated or idiopathic
(without autoimmune markers or HLA association)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Type 1 Diabetes Mellitus• Results in absolute insulin deficiency• Overproduction of glucagon stimulates
glycogenolysis and gluconeogenesis• Glucose levels rise, leading to polyuria,
polydipsia, and polyphagia• FFAs are transformed into ketones, leading to
ketoacidosis
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Type 2 Diabetes Mellitus• Most common form of DM• Non-Caucasian and elderly are disproportionately
affected• Common risk factors include obesity, aging, and
sedentary lifestyle• Insulin resistance and β cell dysfunction lead to a
relative lack of insulin
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Type 2 Diabetes Mellitus• Polyuria, polydipsia, and polyphagia may be more
subtle• Ketoacidosis is uncommon• Hyperglycemic hyperosmolar nonketotic (HHNK)
coma can develop due to severe dehydration, more common in older adults
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Other Specific Types of Diabetes• Genetic defects of β cells—mature onset of
diabetes of the young (MODY)• Genetic defects in insulin action• Disease of the exocrine pancreas• Endocrinopathies• Drug/chemical/infection-induced diabetes
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Gestational Diabetes Mellitus• Disorder of glucose intolerance of variable
severity with onset during pregnancy• Closely resembles type 2 DM• Most likely precipitated by the presence of
placental hormones• Management through dietary counseling,
exercise, and blood glucose/ketone monitoring
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Pre-Diabetes• Impaired glucose tolerance and impaired fasting
glucose tolerance• Intermediate stages between normal glucose
metabolism and diabetes• Represent risk factors for the development of
diabetes and onset of cardiovascular disease
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GLUCOSE INTOLERANCE DISORDERS (CONT.)
Screening for Diabetes• All adults older than age 45 at least every 3 years• Individuals with risk factors should be screened
earlier or more frequently
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS
Acute Hyperglycemia• Commonly caused by alterations in nutrition,
inactivity, or inadequate use of antidiabetic medications
• Symptoms: polyuria, polydipsia, polyphagia, nausea, fatigue, blurred vision
• More prone to infections
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Chronic Hyperglycemia• May lead to systemic changes over time and
increase the risk of other diseases, including metabolic syndrome, hypertension, cardiovascular disease, and stroke
• Complications are categorized as vascular and neuropathic
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Vascular Complications• Macrovascular: damage to large blood vessels;
leads to CVD and stroke• Microvascular: retinopathy and nephropathy from
abnormal thickening of the basement membrane in capillaries; may lead to blindness and renal failure
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Macrovascular Complications• DM is an independent risk factor for coronary
artery disease (CAD)• CAD risk factors, such as dyslipidemia,
hypertension, and impaired fibrinolysis are present in uncontrolled DM and can improve with blood glucose control
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Microvascular Complications• Hyperglycemia disrupts platelet function and
growth of the basement membrane• Thickening of basement membrane may improve
with glycemic control• Risk factors of microvascular complications
include hypertension and smoking
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Neuropathic Complications• Diabetic neuropathy
• Autonomic dysfunction: GI disturbances, bladder dysfunction, tachycardia, postural hypotension, and sexual dysfunction
• Sensory disturbances include carpal tunnel syndrome, paresthesias, or dysesthesias in extremities
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Neuropathic Complications• Excessive glucose is thought to interfere with
myoinositol in neurons and reduced myoinositol in peripheral nerves
• Glycemic control may prevent or improve symptoms of diabetic neuropathy
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
CLINICAL MANIFESTATIONS AND COMPLICATIONS (CONT.)
Complications in Pregnancy• Type 1 DM: higher risk of perinatal infant
mortality and congenital abnormalities• Glycemic control before conception and during
pregnancy may reduce these risks
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION
Nutrition• Cornerstone of diabetes therapy• May involve changing the composition of the diet,
meal patterns and timing, and caloric consumption
• Attention to energy consumption and energy expenditure
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Protein• Used in the repair and growth of tissue• 4 calories/g• Stimulates the secretion of insulin without
increasing plasma blood glucose• Recommended daily allowance 0.8 g protein/kg of
body weight• Excessive protein may cause nephropathy
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Fat• Saturated, monounsaturated, and unsaturated• 9 calories/g• Dietary saturated fat and cholesterol may lead to
hypercholesterolemia• Hypertriglyceridemia increases risk of CAD and
diabetes • Recommendations include limiting saturated fat
to less than 7% of total intake and <200 mg of cholesterol daily
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Carbohydrates• Categorized as monosaccharides and
polysaccharides• 4 calories/g• Carbohydrate intake can be monitored with
carbohydrate counting• Glycemic load and index may also be of benefit
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Alcohol• 7 calories/g• Intake of alcohol should be limited to 1 drink per
day for women, 2 per day for men and avoided in the presence of poor glycemic control, pancreatic/liver/renal disease, severe triglyceridemia, advanced neuropathy, pregnancy, or alcoholism
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Obesity and Eating Disorders• Strongest risk factor for DM• Obesity: a body mass index (BMI) >30 kg/m2
• Recommendations include a nutritionally complete diet, program of maintenance, and exercise
• Bulimia and anorexia may be more common in type 1 DM; careful assessment is warranted
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Exercise• Recommended for all types of DM• Lowers cardiovascular risk factors• May be beneficial toward weight reduction or
maintenance• May lower medication requirements • Type 1 DM at risk of hypoglycemia and
ketoacidosis
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Oral Antidiabetic Agents• Sulfonylureas: induce insulin release by β cells,
augment the action of insulin in glucose disposal, diminish insulin clearance by liver, and reduce hepatic glucose production
• Biguanides: suppress hepatic gluconeogenesis and enhance glucose uptake by peripheral tissues
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Oral Antidiabetic Agents• α-Glucosidase inhibitors: diminish postprandial
hyperglycemia by delaying carbohydrate absorption
• Thiazolidinediones: increase tissue sensitivity to insulin and inhibit hepatic gluconeogenesis
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Incretins and Amylins• Incretins: inhibit enzymatic breakdown of the
incretin hormones, GLP-1, and GIP• Amylins: amylin-mimetic agents used in
conjunction with insulin for the management of glycemia
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Insulin• Required for all patients with type 1 DM and
approximately 35% of those with type 2 DM• Provides replacement of the deficient hormone• Different types: rapid-acting, short-acting,
intermediate-acting, and long-acting
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Hypoglycemia• Most common complication of insulin therapy• Symptoms include pallor, tremor, diaphoresis,
palpitations, and anxiety• Education on symptoms and management of
hypoglycemia should be addressed with all diabetic patients
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Other Complications of Insulin Therapy• Lipoatrophy: hollows in skin surface caused
by the destruction of subcutaneous adipose tissue
• Lipohypertrophy: increase in subcutaneous tissue because of insulin-stimulated growth of adipose tissue at injection sites
• Insulin edema: generalized accumulation of fluid
• Insulin resistance: exacerbated by obesity
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Stress Management• Management of DM can be stressful• Patients with DM at higher risk of depression• Plays an important role in improving quality of life
and reducing impact of stress on glycemic control
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Assessment of Efficacy• Glycosylated hemoglobin is used to determine
long-term glycemic control and to evaluate therapeutic goals
• Values of less than 7% without adverse effect are considered desirable
• Capillary glucose testing• Testing for glucosuria and ketones
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
TREATMENT AND EDUCATION (CONT.)
Education• Considered an essential part of diabetes
treatment• Must be tailored to the individual’s needs• Guided by national standards for the assessment,
setting of objectives, follow-up, and other areas
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
PEDIATRIC CONSIDERATIONS (CONT.)
Goals of Therapy• Achieving normal growth and development• Avoiding acute and chronic complications• Addressing psychosocial issues• Educating children regarding self-care
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
PEDIATRIC CONSIDERATIONS (CONT.)
Acute Complications• Dehydration: diabetic ketoacidosis• DKA frequently precipitated by illness• When blood glucose is >240 mg/dl or during
illness, test for ketones• Hypoglycemia may be difficult to detect; subtle
behavioral changes
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
PEDIATRIC CONSIDERATIONS (CONT.)
Chronic Complications• Rarely manifested before adolescence• Screening for neuropathy and nephropathy
should be ongoing• Counseling on metabolic control before initiation
of pregnancy
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
PEDIATRIC CONSIDERATIONS (CONT.)
Treatment• Insulin requirements are typically 1unit/kg/day• Caloric intake must be adequate to meet needs
for energy expenditure, growth, and maturation
• Child and family need ongoing education and support to develop effective strategies toward reaching desired goals
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GERIATRIC CONSIDERATIONS
Goals of Therapy• Prevention and management of acute and chronic
complications• Attention to psychosocial issues• Education regarding self-care
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GERIATRIC CONSIDERATIONS (CONT.)
Acute Complications• Hyperglycemia: often asymptomatic;
dehydration; increased risk of infection; HHNK coma
• Hypoglycemia can lead to injury
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GERIATRIC CONSIDERATIONS (CONT.)
Chronic Complications• Heart and blood vessel disease• Foot problems• Visual disabilities• Kidney disease
Elsevier items and derived items © 2010, 2005 by Saunders, an imprint of Elsevier Inc.
GERIATRIC CONSIDERATIONS (CONT.)
Treatment• Oral agents should be chosen carefully with
consideration of renal and hepatic function• Short-acting agents are preferable• Insulin therapy may require adaptive devices• Exercise and meal planning are advised