Long-term Complications of Type 2 Diabetes

2. Hyperglycemia Macrovascular Disease Microvascular Disease Damage to medium and large blood vessels Damage to small blood vessels Coronary Artery Disease Cerebrovascular Disease Peripheral vascular disease Retinopathy Nephropathy Neuropathy Long-term Complications of Type 2 Diabetes

3. Selected Glucose Regulatory Hormones • Insulin • Secreted by beta cells of pancreas • Decreases glucose blood levels by facilitating glucose entry into certain cells to be used for energy or energy storage • Glucagon • Secreted by alpha cells of pancreas • Increases glucose blood levels via gluconeogenesis and glycogenolysis in the liver • Incretins • Gut hormones, release stimulated by food ingestion • Glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) are the predominant incretins • Cortisol • An essential hormone produced by the adrenal glands • Levels rise with stress and lead to an increase in glucose levels • Epinephrine • “Fight or flight” hormone produced by the adrenal glands • Levels rise with stress and lead to an increase in glucose levels • Somatostatin • Secreted by the delta cells of the pancreas • Inhibits the release of many hormones including insulin, glucagon, and growth hormone

4. Key Types of Lipids Triglycerides • Most common fat in diet and in the body • Main role is energy storage in fat cells • Comprised of 3 fatty acids and a glycerol molecule • Carried in the blood primarily by VLDL Cholesterol • Found in foods of animal origin • Used to build cell membranes, steroid hormones, and bile salts • Carried in the blood by LDL and HDL Lipoproteins • Molecules of lipid (triglycerides and cholesterol) assembled with protein • Transport vehicles for triglycerides and cholesterol • LDL - low density lipoprotein • HDL - high density lipoprotein • VLDL - very low density lipoprotein

5. Lipid Metabolism • Ingested fats are broken into fatty acids and other compounds in the intestines via lipolysis • Fatty acids absorbed by the intestines are combined with glycerol to form triglycerides in a process termed lipogenesis • Once in the blood, the triglycerides are broken back down into fatty acids and glycerol • Fatty acids are • used for immediate energy production OR • stored in the form of triglycerides for later energy use

6. Lipoproteins: Major Types • LDL - Low-density lipoprotein • transports about 75% of the cholesterol in the blood from the liver to the body tissues, where it is used for cell membranes, synthesis of steroid hormones • also known as "bad cholesterol“ as it may deposit cholesterol in blood vessels, forming plaques that lead to coronary artery disease • HDL - High-density lipoprotein • removes excess cholesterol from body cells and transports it to the liver for elimination • also known as "good cholesterol" as it prevents accumulation of cholesterol in blood vessels and is associated with a reduced risk of coronary artery disease • VLDL – Very Low-density lipoprotein • formed in the liver and contain mostly lipids that are made in the body • transports about 50% of the triglycerides synthesized in the liver to adipose tissue for storage

7. Glucose the primary circulating sugar in the blood and the major energy source of the body – used to produce ATP Gluconeogenesis the formation of new glucose from protein or fat (to store energy)‏ the breakdown of glucose (to produce energy)‏ Glycolysis Glycogen the main form of carbohydrate storage primarily in the liver and muscle tissue; readily converted to glucose to satisfy its energy needs Glycogenesis formation of glycogen from glucose (to store energy)‏ Glycogenolysis breakdown of glycogen to glucose (to produce energy)‏ Lipid fat; found almost exclusively in foods of animal origin and continuously synthesized in the body Lipogenesis the formation of lipids (to store energy)‏ Lipolysis the breakdown of lipids (to produce energy)‏ Glucose and Lipid Metabolism: Definitions of Key Terms

8. Protein Metabolism • Ingested proteins are broken down into amino acids, absorbed into the blood, and taken up by cells of the body • Within cells, amino acids are used to synthesize other proteins the body needs. • Proteins can be: • Converted to fat or glycogen for energy storage • Broken down and used to make glucose for energy needs (gluconeogenesis)‏

9. Progression of Type 2 Diabetes:Nondiabetic State 1. Adequate beta cell function 2. Normal insulin sensitivity 3. Adequate plasma insulin 4. Normal blood glucose Normal Glucose Levels FPG <100 mg/dL Time

10. Progression of Type 2 Diabetes: Early Abnormalities in Deteriorating Glucose Homeostasis 3. Impaired beta cell function 2. Hyperinsulinemia 1. Decreased insulin sensitivity 4. Normal blood glucose Normal Glucose Levels FPG <100 mg/dL Time

11. Progression of Type 2 Diabetes: Prediabetes 2. Compensatory hyperinsulinemia 4. Beta cell dysfunction 3. Blood glucose rises 1. Decreasing insulin sensitivity Prediabetes Normal Glucose Levels Glucose Levels FPG <100 mg/dL IFG = FPG = 100 to 125 mg/dL IGT = OGTT = 140 to 199 mg/dL Time

12. Progression of Type 2 Diabetes: Type 2 Diabetes 1. Hyperglycemia 3. Declining insulin levels 2. Progressive beta cell failure 5. Beta cell failure 4.Decreased insulin sensitivity persists or worsens Prediabetes Diabetes Normal Glucose Levels Glucose Levels Glucose Levels FPG <100 mg/dL IFG = FPG = 100 to 125 mg/dL - Symptoms plus IGT = OGTT = 140 to 199 mg/dL casual glucose ≥200 mg/dL - FPG ≥126 mg/dL - OGTT ≥200 mg/dL Time