Endocrine - Diabetes

Question 1

Pancreatic Islet of Langerhands

Answer 1

(inner portion of pancreas) – endocrine portion
o Alpha cell – glucagon – secretion is inhibited by insulin – NOT controlled by glucose
o Beta cell – insulin and C peptide
o Delta cell – somatostatin

Question 2

Effects of Insulin

Answer 2

o Decreased: appetite, glucagon, decrease extracellular potassium levels
o Increased: glucose uptake, glycolysis, glycogen synthesis, triglyceride synthesis, amino acid uptake, protein synthesis

Question 3

Effects of Lack of Insulin

Answer 3

• primarily mediated by glucagon
  o Decreased: glucose uptake, protein synthesis
  o Increased: appetite, glucagon, blood glucose, gluconeogenesis, lipolysis, protein breakdown, glycogenolysis, ketone body production (ketoacidosis)

Question 4

Insulin Effect Mechanism

Answer 4

o Binds to dimeric receptor resulting in intracellular events
o GLUT4 glucose transporter inserted into plasma membrane

Question 5

Insulin Secretion Mechanism

Answer 5

o Secretion triggered by rising blood glucose levels
o Glucose uptake by GLUT2 transporter leading to increase in cellular ATP  ATP binds to ATP-potassium channel preventing K+ from leaking out  cell depolarization  Ca+ influx  exocytotic release of insulin from storage granules

Question 6

Type 1 Diabetes

Answer 6

(10%) – autoimmune destruction of beta-cells (no insulin = HIGH glucagon)
o Clinical: onset < 20 years old, normal weight, decreased blood insulin, anti-islet cell antibodies, ketoacidosis is common
o Genetics: <50% concordance in twins; HLA-D linked
o Islet Cells: insulitis early, marked atrophy and fibrosis, beta-cell depletion
o Clinical symptoms do not arise until sufficient destruction (50%) has occurred

Question 7

Type 2 Diabetes

Answer 7

(90%) – insulin resistance
o Clinical: onset > 30 years old, obese, increase blood insulin, ketoacidosis is RARE
o Genetics: >90% concordance in twins; NO HLA associations
o Pathogenesis: insulin resistance, relative insulin deficiency
o Islet Cells: no insulitis, focal atrophy and amyloid deposits, mild beta-cell depletion
o Progressive loss of insulin sensitivity, resulting in progressive increase in insulin production
 Maintains normal serum glucose but results in hyperinsulinemia
 As insulin insensitivity falls, hyperinsulinemia is not sufficient to maintain normal glycemia and hyperglycemia results
 Chronic hyperglycemia (glucose toxicity) results in beta-cell destruction and loss of insulin production; typically requires more than 10 years

Question 8

Other Types of Diabetes

Answer 8

(<1%)
o Maturity-onset diabetes of youth – 2% of diabetics under age of 15
 Genetic defect in insulin production or release
 Often misdiagnosed for Type I diabetes
 Treatment: oral hypoglycemic drug
o Gestational Diabetes Mellitus – diabetes identified during pregnancy
 Most likely pre-diabetic prior to birth
 Possibly caused by chorionic somatomammotropin
o Various other endocrine disorders – Cushing’s, acromegaly, pheochromocytoma, etc.

Question 9

Oral Glucose Test

Answer 9

o Normal fasting plasma glucose levels < 100mg/dl
o Fasting plasma glucose level > 126mg/dl
o OR Plasma glucose levels in excess >200mg/dl after 2 hours during tests

Question 10

Pre-Diabetes

Answer 10

o Also called impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) depending on test used to diagnose it (some people have both)
o IFG – blood glucose level is 100-125mg/dl after an overnight fast
o IGT – blood glucose level is 140-199 after 2 hour oral glucose tolerance test
o 40% of adults between 40-75 have pre-diabetes
o 10% of pre-diabetics develop into type 2 diabetes

Question 11

Acute Complications

Answer 11

o Acute Complications – hypoglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic nonketotic syndrome, glucosuria/polyuria
 Hyperosmolar Hyperglycemic Nonketotic Syndrome – only affects Type II diabetics
• Result of glucose in blood drawing water out of cells

Question 12

Chronic Complications

Answer 12

 Hyperglycemia & Nonenzymatic glycosylation-advanced glycosylation end-products
• Glucose binds to and damages proteins (ex: HbA1c – glycosylated hemoglobin)
o Higher levels of HbA1c = higher risk of retinopathy, nephropathy, neuropathy, microalbuminuria
 Associated with Type 1 diabetics and NOT Type 2 diabetics
 Microvascular disease – diabetic retinopathy, nephropathy, cardiomyopathy
 Macrovascular disease – coronary artery disease, stroke, peripheral arterial disease
 Increase activity of polyol/sorbitol pathway - diabetic neuropathy, cataracts
 Other – glaucoma, infection

Question 13

Ketogenesis

Answer 13

– generation of ketone bodies from acetyl-CoA,
o Increased urine output leads to dehydration and hypovolemic shock
o Enzymes involved are unique to hepatocytes
o Mitochondrial HMG-CoA is essential intermediate
o Initial product acetoacetic acid can decompose to beta-hydroxybutyrate or acetone

Question 14

Diabetic Retinopathy

Answer 14

o Diabetes causes retinal damage and leads to blindness
o Prevalence is higher in Type 1 (40%) than in Type 2 (20%)
o Earliest Phase of Disease – background diabetic retinopathy – arteries in retina become weakened and leak, forming small, dot-like hemorrhages
o Later Stage – proliferative diabetic retinopathy – circulation problems cause areas of retina to become oxygen-deprived (ischemic) – new fragile vessels develop as circulatory system attempts to maintain adequate oxygen levels within retina BUT the vessels will hemorrhage easily

Question 15

Diabetic Nephropathy

Answer 15

o Leakiness of glomerular capillaries: microalbuminuria-proteinuria
o Glomerulosclerosis, tubulointerstitial fibrosis, arteriolar sclerosis
o Renal failure, hypertension, cardiovascular disease
o Kidney disease – granular surface, decreased function, smaller size, high urine protein

Question 16

Diabetic Nephropathy Characteristics

Answer 16

o 30% of diabetics will develop diabetic nephropathy
o Diabetes (type 1 and 2) is leading cause of kidney failure
o Greatest rate of progression seen in patients with poor control of their blood pressure
o Main treatment (once proteinuria is diagnosed) – keep blood pressure under control
o Treatment: angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers
o Uncontrolled diabetes often requires dialysis  diabetic patients do worse

Question 17

Diabetic Neuropathy

Answer 17

o Peripheral Neuropathy – causes pain or loss of feeling in toes, feet, legs, hands, and arms
o Diabetic Foot – blisters/sores appear on numb areas of foot b/z pressure or injury goes unnoticed
 If untreated – infection may spread to bone and foot may need to be amputated
o Autonomic Neuropathy – causes changes in digestion, bowel and bladder function, sexual response, and perspiration
 Can also affect nerves that serve the heart and control blood pressure
o Focal Neuropathy – sudden weakness of one nerve or group of nerves, causing weakness or pain
 Any nerve in body may be affected

Question 18

Gestational Diabetes

Answer 18

o During pregnancy, hormonal changes can cause impaired insulin sensitivity
o Glucose levels are normally lower during pregnancy so cutoff levels for diagnosis of diabetes in pregnancy are lower
 Fasting blood glucose = 95mg/dl, 1-hour level = 180mg/dl, 2-hour level = 155mg/dl, 3-hour level = 40mg/dl
o Usually occurs between 24-28 weeks of pregnancy
o If poorly controlled, can cross the placenta and give the baby hyperglycemia
o Babies from mothers with gestational diabetes have higher risk for developing hypertension and cardiovascular disease
o Resolves itself following childbirth
o Once you’ve had gestational diabetes, chances are it will return in future pregnancies