Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 50 Diabetes Mellitus and the Metabolic Syndrome

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Glucose, Fats, and Protein Energy needs in the body The liver with hormones from the endocrine pancreas that regulates energy production Glucose is metabolized to CO 2 and H 2 O. –4 kcal/g Fat is metabolized to glycerol and fatty acids. –9 kcal/g Protein is metabolized to amino acids. –4 kcal/g

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Tissue Types and Functions of the Pancreas The acini –Secrete digestive juices into the duodenum The islets of Langerhans –Secrete hormones into the blood –Composed of beta cells that secrete insulin, alpha cells that secrete glucagon, and delta cells that secrete somatostatin

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Insulin and Glucagon on Glucose Insulin –Increases glucose transport into skeletal muscle and adipose tissue –Increases glycogen synthesis –Decreases gluconeogenesis Glucagon –Promotes glycogen breakdown –Increases gluconeogenesis

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Insulin on Glucose, Fats, and Protein Anabolic in nature Promotes glucose uptake by target cells and provides for glucose storage as glycogen Prevents fat and glycogen breakdown Inhibits gluconeogenesis and increases protein synthesis

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Actions of Glucagon on Glucose, Fats, and Protein Catabolic in nature Increases transport of amino acids into hepatic cells Increases breakdown of proteins into amino acids for use in gluconeogenesis Increases conversion of amino acids into glucose precursors

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Other Hormones Affecting Blood Glucose Catecholamines –Epinephrine and norepinephrine –Help to maintain blood glucose levels during periods of stress Growth hormone –Increases protein synthesis in all cells of the body, mobilizes fatty acids from adipose tissue, and antagonizes the effects of insulin

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Other Hormones Affecting Blood Glucose (cont.) Glucocorticoids –Critical to survival during periods of fasting and starvation –Stimulate gluconeogenesis by the liver

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Insulin is _______________ and glucagon is ______________. −A. catabolic −B. anabolic

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer Insulin is anabolic and glucagon is catabolic.

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Diabetes Type 1 results from –Loss of beta cell function –An absolute insulin deficiency Type 2 results from –Impaired ability of the tissues to use insulin –A relative lack of insulin or impaired release of insulin in relation to blood glucose levels

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Diabetes Mellitus Prediabetes—impaired fasting plasma glucose and impaired glucose tolerance Disorder of carbohydrate, protein, and fat metabolism –Results from an imbalance between insulin availability and insulin need Can represent –An absolute insulin deficiency –Impaired release of insulin by the pancreatic beta cells –Inadequate or defective insulin receptors –Production of inactive insulin or insulin that is destroyed before it can carry out its action

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Hyperglycemia is a complication of ________________. −A. diabetes type 1 −B. diabetes type 2 −C. both

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C. both Rationale: Hyperglycemia is a complication of both conditions, but is thought to be causative in type 2, and transient in type 1.

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Subdivisions of Type 1 Diabetes Type 1A –Immune-mediated diabetes Type 1B –Idiopathic diabetes

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Involved in the Development of Type 1A Diabetes Genetic predisposition (diabetogenic genes) A hypothetical triggering event that involves an environmental agent that incites an immune response Immunologically mediated beta cell destruction

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Idiopathic Type 1B Diabetes Those cases of beta cell destruction in which no evidence of autoimmunity is present Only a small number of people with type 1 diabetes fall into this category; most are of African or Asian descent. Type 1B diabetes is strongly inherited. People with the disorder have episodic ketoacidosis due to varying degrees of insulin deficiency with periods of absolute insulin deficiency that may come and go.

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Metabolic Abnormalities Contributing to Hyperglycemia in Type 2 Diabetes Impaired beta cell function and insulin secretion Peripheral insulin resistance Increased hepatic glucose production

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Beta Cell Dysfunction in Patients with Diabetes An initial decrease in the beta cell mass Increased beta cell apoptosis/decreased regeneration Long-standing insulin resistance leading to beta cell exhaustion Chronic hyperglycemia can induce beta cell desensitization (“glucotoxicity”). Chronic elevation of free fatty acids can cause toxicity to beta cells (“lipotoxicity”). Amyloid deposition in the beta cell can cause dysfunction.

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Metabolic Syndrome and Type 2 Diabetes Metabolic syndrome – Triglycerides – HDL – Hypertension – Systemic inflammation – Fibrinolysis – Abnormal function of the vascular endothelium – Macrovascular disease Obesity and insulin resistance Increased resistance to the action of insulin Impaired suppression of glucose production by the liver Hyperglycemia and hyperinsulinemia

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Metabolic syndrome is most often related to __________________. −A. diabetes type 1 −B. diabetes type 2

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer B. diabetes type 2 Rationale: Due to the high levels of glucose and the increased appetite for carbohydrates

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins The Three Polys of Diabetes Polyuria –Excessive urination Polydipsia –Excessive thirst Polyphagia –Excessive hunger

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Other Symptoms of Hyperglycemia Weight loss Recurrent blurred vision Fatigue Paresthesias Skin infections

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Blood Tests Fasting blood glucose test Casual blood glucose test Capillary blood tests and self-monitoring of capillary blood glucose levels Glycated hemoglobin testing

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatment Plans for Diabetes Nutrition therapy Exercise Anti-diabetic agents

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Oral Antidiabetic Agents Sulfonylureas Repaglinide and nateglinide Biguanides α-Glucosidase Inhibitors Thiazolidinediones

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Three Principal Types of Insulin Short-acting Intermediate-acting Long-acting

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Acute Complications of Diabetes Diabetic ketoacidosis –Hyperglycemia –Ketosis –Metabolic acidosis Hyperosmolar hyperglycemic state Hypoglycemia

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Definitive Diagnosis of DKA Hyperglycemia (blood glucose levels >250 mg/dL) Low bicarbonate (<15 mEq/L) Low pH (<7.3) Ketonemia (positive at 1: 2 dilution) Moderate ketonuria

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Characteristics of Hyperosmolar Hyperglycemic State (HHS) Hyperglycemia (blood glucose >600 mg/dL) Hyperosmolarity (plasma osmolarity >310 mOsm/L) Dehydration The absence of ketoacidosis Depression of the sensorium

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Contributing to Hyperglycemia Increased resistance to the effects of insulin Excessive carbohydrate intake

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Complications of Diabetes Disorders of the microvasculature –Neuropathies, nephropathies, and retinopathies –Distal symmetric neuropathy and foot ulceration Macrovascular complications

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Pathologic Changes Observed with Diabetic Peripheral Neuropathies Thickening of the walls of the nutrient vessels that supply the nerve –Leading to the assumption that vessel ischemia plays a major role in the development of neural changes Segmental demyelinization process that affects the Schwann cell Accompanied by a slowing of nerve conduction

Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classification of Diabetic Peripheral Neuropathies Somatic –Polyneuropathies (bilateral sensory) –Mononeuropathies –Amyotrophy Autonomic –Impaired vasomotor function –Impaired gastrointestinal function –Impaired genitourinary function –Cranial nerve involvement