G & E EXAM 1

im so sorry :*(

metformin

first line therapy for patients with TYPE 2 diabetes

metformin

decreases hepatic GLUCONEOGENESIS

GLP-1 receptor agonist

mimics ENDOGENOUS hormone that stimulates insulin and inhibits glucagon

liraglutide

GLP-1 receptor agonist example

slow gastric emptying and increase satiety

other effects besides insulin and glucagon of GLP-1 receptor agonist

SGLT-2 inhibitors

inhibit reabsorption of glucose in proximal tubules 

bloating, nausea, diarrhea

ADRs of metformin

sulfonylureas

block K channel in pancreatic cell, increase insulin release

hypoglycemia and weight gain

ADRs of sulfonylureas

DDP-4 inhibitors

block enzyme that breaks down incretin hormones (GLP-1 and GIP)

alpha-glucosidase inhibitor

blocks breakdown of carbohydrates in small intestine

retinopathy, nephropathy, neuropathy

microvascular long term complications of diabetes

diabetic nephropathy

leading cause of end stage renal disease

diabetic retinopathy

leading cause of blindness in working age adults

stroke (cerebrovascular disease), heart disease, peripheral vascular disease

macrovascular long term complications of diabetes

retinal, urine (proteinuria), foot exam

screenings to decrease microvascular complications of diabetes

cardiovascular disease (CVD)

primary cause of DEATH in diabetes mellitus

statins

best way to decrease the MACROVASCULAR complications of diabetes mellitus

type 1 diabetes

insulin REQUIRED for survival

insulin

ONLY means of treating type I diabetes

sudden onset of polyuria, polydipsia, weight loss, and/or DKA

symptoms of type I diabetes

type I diabetes

lymphocytes infiltrate islet cells and attack insulin-producing beta cells

lack of energy storage and imbalance between insulin and glucose

result of insulin deficiency in Type 1 diabetes

lipolysis, gluconeogenesis, glycogenolysis

mechanisms that lead to hyperglycemia in Diabetic Ketoacidosis (DKA)

hyperglycemia

cause of the osmotic diuresis that occurs in DKA

Ketogenesis

caused by breakdown of FATTY ACIDS

DKA (diabetic ketoacidosis)

typical in type I diabetes, absolute insulin deficiency leads to fat breakdown and ketone production

HHS (hyperosmolar hyperglycemic syndrome)

typical in type 2 diabetes, relative insulin deficiency leads to hyperglycemia and severe dehydration

≤7%

goal HbA1c for people on insulin

diabetes mellitus

fasting or post meal HYPERGLYCEMIA due to absolute or relative insulin deficiency

type 1 diabetes

ABSOLUTE insulin deficiency

type 1 diabetes

an autoimmune condition where beta cells are destroyed

type 1 diabetes

typically presents in younger individuals with abrupt symptoms

type 2 diabetes

RELATIVE insulin deficiency due to insulin resistance

type 2 diabetes

typically present in older individuals with gradual onset

pree-receptor, receptor, and post-receptor

3 types of insulin resistance

polyuria, polydypsia, weightloss, fatigue

symptoms of Diabetes

polyuria

excessive urination associated with diabetes

polydypsia

excessive thirst typically associated with diabetes

acanthosis nigricans (thickened skin discoloration)

typical clinical sign of insulin resistance in type 2 diabetes

induces beta cells to produce more insulin which eventually leads to failure

how does insulin resistance lead to type 2 diabetes?

HbA1c, fasting plasma glucose, oral glucose tolerance

What tests are used to diagnosis Diabetes Mellitus?

hemoglobin a1C

reflects average blood glucose over ~3 months

fasting plasma glucose

measures blood sugar after at least 8 hours of fasting

oral glucose tolerance

blood glucose measured before and 2 hours after drinking 75g of glucose solution

HbA1C

form of hemoglobin modified by exposure to glucose

increased  blood glucose over past 3 months

what does a high HbA1c indicate

Pre-Diabetes

elevated glucose levels indicating body is STARTING to have trouble regulating sugar

metabolic syndrome

collection of related factors that predispose an individual to the development of type 2 diabetes and CVD

abdominal obesity, elevated triglycerides, low HDL, elevated BP, and elevated fasting glucose

criteria for the Metabolic Syndrome

insulin resistance

underlying defect in the Metabolic Syndrome

26.8

% of adults in the US over 65 that have Type 2 diabetes

family history, polyuria, polydipsia, frequent UTI

clinical features of Type 2 diabetes

decreased glucose uptake (hepatic and peripheral), increased hepatic glucose production, decreased incretins

what happens when there is DECREASED INSULIN activity

hyperglycemia

what does decreased insulin activity lead to?

GLP-1 and GIP/ incretin hormones

INHIBIT glucagon release and INCREASE insulin release

GLP-1

produced by L cell in ileum in response to food

GIP

produced by K cells in duodenum/jejunum in response to food

incretin hormones (GLP-1 and GIP)

stimulate release of insulin from pancreas after meal ingestion

hypoglycemia

glucose levels below normal range (<70mg/dL)

increased insulin and decreased counter regulatory hormones

what leads to hypoglycemia

sweating, anxiety, nausea, palpitation, tachycardia

adrenergic/cholinergic symptoms of hypoglycemia that occur at around 58mg/dL

behavior changes, vision/speech changes, confusion, dizziness, lethargy, seizure

neuroglycopenic symptoms of hypoglycemia that occur around 49-51 mg/dL

alcohol, malnutrition, kidney/liver failure, severe illness

causes of non-insulin-mediated hypoglycemia

liver (primary)  and kidney 

What organs carry out gluconeogenesis

insulinoma

insulin-secreting tumor of pancreatic beta cells 

insulinoma

elevated insulin even in fasting state could indicate what?

hyperglycemia

elevated glucose level above normal range

>125

diabetic fasting blood sugar

>200

diabetic post-meal blood sugars

glucagonoma

tumor of pancreatic alpha cells

glucagonoma

elevated glucagon regardless of glucose status could indicate?

hyperglycemia, weight loss, necrolytic migratory erythema

symptoms of glucagonoma

somatostatinoma, acromegaly, Cushing's, phenochromocytoma

other conditions besides diabetes that can cause hyperglycemia

fed state

state with increased insulin, decreased glucagon

fed state

state in which there is GLUCOSE UPTAKE by liver, gut, and peripheral tissues

insulin

INCREASED in fed state

insulin

increases energy storage and glucose uptake, inhibits lipolysis and ketosis

insulin

decreases hepatic glucose output

beta cell

secretes insulin when stimulated by glucose

phase 1 of insulin secretion

rapid release of preformed insulin from storage granules

phase 1 of insulin secretion

triggered by immediate rise in blood glucose post meal and continues for 10-15 min

phase 2 insulin secretion

Sustained, slower release of insulin to match ongoing glucose levels

binds insulin receptor, signals Glut4 (glucose transporter) translocation to cell membrane 

how does insulin facilitate glucose uptake into cells

insulin

acts to STORE energy

insulin

stimulates GLYCOGEN SYNTHESIS and storage

oppose insulin, prevent hypoglycemia, fuel during starvation

functions of counter-regulatory hormones

glucagon, epinephrine, growth hormones, cortisol, and somatostatin

Types of counter-regulatory hormones to RAISE blood sugar

fasting state

state with decreased insulin and increased glucagon

glycogenolysis, gluconeogenesis, lipolysis, ketogenesis  

changes during fasting state that maintain glucose levels

gluconeogenesis

production of glucose by liver from amino acids, lactate, and glycerol

glycogenolysis

glycogen in liver converted into glucose and release into blood stream

after 12-24 hour fast

when do glycogen stores become depleted

ketogenesis, lipolysis, gluconeogenesis

What happens when glycogen stores are depleted?

ketogenesis

liver converts triglycerides into fatty acids and glycerol leading to production of ketone bodies and glucose

pancreatic alpha cell

secretes GLUCAGON during fasting state

glucagon

INCREASES blood glucose levels during FASTING state

glycogenolysis, lipolysis, ketogenesis, gluconeogenesis

effects of glucagon

lipoproteins

complexes that TRANSPORT fat through the bloodstream

transport of cholesterol and triglycerides

role of lipoproteins