Long-term Complications of Type 2 Diabetes Hyperglycemia Damage to medium and large blood vessels Damage to small blood vessels Macrovascular DiseaseMicrovascular.

Long-term Complications of Type 2 Diabetes

Hyperglycemia

Damage to mediumand large blood vessels

Damage to small blood vessels

Macrovascular Disease Microvascular Disease

Coronary Artery Disease

CerebrovascularDisease

Peripheral vascular disease Retinopathy Nephropathy Neuropathy

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

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

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

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

Glucose and Lipid Metabolism: Definitions of Key Terms

fat; found almost exclusively in foods of animal origin and continuously synthesized in the body

Lipid

the breakdown of lipids (to produce energy)Lipolysis

the formation of lipids (to store energy)Lipogenesis

breakdown of glycogen to glucose (to produce energy)Glycogenolysis

formation of glycogen from glucose (to store energy)Glycogenesis

the main form of carbohydrate storage primarily in the liver and muscle tissue; readily converted to glucose to satisfy its energy needs

Glycogen

the breakdown of glucose (to produce energy)Glycolysis

the formation of new glucose from protein or fat (to store energy)Gluconeogenesis

the primary circulating sugar in the blood and the major energy source of the body – used to produce ATP

Glucose

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)

Progression of Type 2 Diabetes: Nondiabetic State

1. Adequate beta cell function

2. Normal insulin sensitivity

3. Adequate plasma insulin

4. Normal blood glucose

Time

NormalGlucose Levels

FPG <100 mg/dL

3. Impaired beta cell function

2. Hyperinsulinemia1. Decreased

insulin sensitivity

4. Normal blood glucose

Time

NormalGlucose Levels

FPG <100 mg/dL

Progression of Type 2 Diabetes: Early Abnormalities in Deteriorating Glucose

Homeostasis

2. Compensatory hyperinsulinemia

4. Beta cell dysfunction

3. Blood glucose rises

1. Decreasing insulin sensitivity

Time

NormalGlucose Levels

FPG <100 mg/dL

PrediabetesGlucose Levels

IFG = FPG = 100 to 125 mg/dLIGT = OGTT = 140 to 199 mg/dL

Progression of Type 2 Diabetes: Prediabetes

1. Hyperglycemia

4. Decreased insulin sensitivity persists or worsens

3. Declining insulin levels

5. Beta cell failure

Time

PrediabetesGlucose Levels

DiabetesGlucose Levels

IFG = FPG = 100 to 125 mg/dLIGT = OGTT = 140 to 199 mg/dL

- Symptoms plus casual glucose ≥200 mg/dL- FPG ≥126 mg/dL- OGTT ≥200 mg/dL

NormalGlucose Levels

FPG <100 mg/dL

Progression of Type 2 Diabetes: Type 2 Diabetes

2. Progressive beta cell failure