Week 2 - Endocrine Flashcards
Actions of Insulin
(stimulated by high blood glucose, inhibited by somatostatin) (made by beta cells in pancreas)
Liver: glucose to glycogen
Fat: fatty acid + glycerol to fat
Muscle: amino acids to protein
GLUT4 in muscle and adipose is stimulated by insulin to uptake glucose
Glucagon actions
prevents hypoglycemia (made in alpha cells in pancreas) (stim by glucose, insulin, etc, inhibited by amino acids) Liver: glycogen to glucose, glucose out into blood, amino acids in Adipose: release free fatty acids (makes ketoacids in the liver)
Glucagon-Like peptides (GLPs)
secreted by gut in response to feeding
acute: increases insulin response to glucose
Chronic: increases beta-cell mass
Diagnosis of DM
HbA1C more than 6.5 (norm under 5.7)
fasting glucose more than 126 (norm under 100)
2hr glucose post 75g glucose over 200 (norm under 140)
random glucose over 200
Medications for T2DM
Insulin- most potent
Sulfonylurea- (glipizide, glyburide, glimepiride) stim insulin release via K-channel
Meglitinide- (repaglinide, nateglinide) stim insulin release via K-channel
Biguanide- (metformin) decrease systemic glucose output - can cause lactic acidosis(don’t use in renal insuff)
Diagnose metabolic syndrome
waist circum over 40in or 35in triglyceride over 150 HDL under 40 or 50 BP over 130/85 fasting glucose over 100
Mechanisms of insulin resistance
Inflammation: cytokines- IL1, TNFa, IL6- JNK- IRS-1- inhibits insulin receptor fxn
Lipid overload: fatty acids- fatty acyl coa- increase DAGS (diacylglycerols)- increase nPKC and serine kinases- IRS-1- inhibit insulin action
Lipotoxicity: deposition of lipids and fat in liver and skeletal muscle, and also in islet beta cells
Tx of metabolic syndrome
Tx obesity: orlistat (inhibits lipases) Tx HTN: ACE inhibitors or ARBs Tx LDL: statins or ezetimibe Tx trigs and HDL: fibrates or niacin Tx dm: metformin Tx cardio risk: aspirin
Pathophys of T1DM in kids
environmental trigger (virus)- B-cell antigen (GAD65)- cytokines- CD4- Th1- CD8 CTLs- attack pancreas start symptoms when 90% beta cells are gone
Type 1 DM
labs: low Na, low K (but may be high in serum), low bicarb (ketoacidosis), phosphaturia
Biochem: dehydration and hypovolumemia from severe hyperglycemia thus osmotic diuresis,, also from vomiting and metabolic acidosis from ketoacids from starvation mode from lack on intracellular glucose
Insulin preps
short: aspart, lispro, glulisine (monomeric)
Regular
Longish: NPH (forms hexamers)
Long: detemir, glargine (forms microprecipitate)
Sides: hypoglycemia, lipohypertrophy, atherosclerosis, cancer risk
Insulin overdose (hypoglycemia)
mild: increased sympathetic tone, give oral fast carbs
moderate: neuro sx, give fast carbs sugar-gel
severe: seizure, coma, give glucagon injection
Hypoglycemia
generally less than 70 mg/dl glucose
Whipple’s Triad: sx of hypogly, low measured plasma glucose, resolution of sx with increased glucose
Hormone resopnse: Insulin decreases, glucagon increases (gluconeogenesis in liver), epinephrine increases (b2-adrenergic increases substrate), cortisol and growth hormone increase (limit glucose utilization and increase gluconeogenesis)
Sx: neurogenic (tremor, anxiety, sweating), neuroglycopenic (behavior, psychomotor, visual, seizures, coma)
Causes: insulin/drugs, critical illness, cortisol def, insulinoma, autoimmune insulin
Dx: use 72-hr supervised fast test
Insulinoma
hypoglycemia
mostly benign, solitary, small
dx by hormone studies when hypoglycemic
72-hr fast test for hypoglycemia
Test for: glucose (if low then hypoglycemia) Insulin (if high then insulinoma or drugs or autoimmune) c-peptide (only in endogenous insulin) sulfonylurea (if present then drugs) proinsulin (elevated in insulinoma) B-hydroxybutyrate (low in insulinoma) response to IV glucagon (if respond then hyperinsulin)
MEN1
11q13, autosomal dominant
Parathyroid adenoma
pituitary adenoma
enteropancreatic tumors
DX: 2 or more assoc tumors, one tumor and 1st deg relative with MEN1, has MEN1 mutation
NO genotype/phenotype correlation
-identifying mutation allows for genetic counseling and screening family members
MEN2
10-10q11.2, autosomal dominant, RET mutations Medullary thyroid cancer pheochromocytoma A: parathyroid hyperplasia B: mucosal neuromas, marfanoid habitus -Have typical facies Genotype predicts severity and risk
Sulfonylureas
Glipizide, Glyburide, Glimeprimide
for diabetes: stimulates insulin secretion by pancreas by inactivating a K-channel, influx of Ca
Sides: rashes and drug interaction with warfarin, hypoglycemia
Biguanide (Metformin)
for diabetes (1st line)
sensitizes liver to insulin-> decreased hepatic gluconeogenesis
Sides: GI probs, lactic acidosis
Contra: renal insuff, CHF, hypoxia, liver dysfxn
Also lowers CV and cancer risks
Thiazolidinediones
Pioglitazone, rosiglitazone
for diabetes
PPAR receptor agonists, make peripheral tissues more sensitive to insulin
Sides: liver tox, weight gain, fluid retention, bladder cancer
Contra: CHF
Alpha-Glucosidase inhibitors
acarbose
for diabetes, nhibits enteric enzymes that break down complex carbs
reduces post-prandial hyperglycemia
sides: bloating, flatulence
GLP-1 analogs
exenatide, liraglutide
for diabetes
GLPs are stimulated by eating and augments response to insulin, increase beta cell mass, inhibits glucagon, promotes weight loss
DPP-4 inhibitors
sitagliptin
for diabetes
DPP-4 degrades GLP-1 so these drugs prolong GLP action
SGLT-2 inhibitors
Canagliflozin
for diabetes
inhibits Na-glucose transporter in the kidney proximal tubule, thus increases renal glucose loss
Sides: yeast infxn, dehydration
