Glucose homeostasis/T2DM

"diabetes day 1-3 worksheets"

describe the effect of what is going on when there is high glucose- fed state

high glucose → high insulin, low glucagon → glucose uptake by the liver, gut, peripheral tissues → dec endogenous insulin production

what secretes insulin

pancreatic beta cells

what are the physiological actions of insulin the body

• inc peripheral glucose uptake

• inc energy storage

• inhibition of lipolysis and ketosis

• dec hepatic glucose output

what is the first step of insulin secretion

rapid release of preformed insulin from storage granules (post-meal response), begins within 2 min of nutrient ingestion and continues for 1-15 min as an immediate response

what is the second step of of insulin secretion

involves synthesis of new insulin from stored cytoplasmic insulin, more prolonged response to glucose control

what are the counter-regulatory hormones that raise blood sugar

• somatostatin

• growth hormones

• cortisol

• epinephrine

• glucagon

what secreted somatostatin

many tissues

funx of somatostatin

reduces insulin and glucagon

what secretes growth hormone

the pituitary gland

funx of growth hormone

stimulates glycogenolysis; antagonizes the effect of insulin on glucose uptake in the peripheral tissues

funx of cortisol

acute impairment of insulin secretion and inc in hepatic glucose output

funx of insulin

inc hepatic glucose production, dec insulin effectiveness

funx of glucagon

mobilizes stored energy: glycogenolysis, lipolysis, ketone formation, gluconeogenesis

what is happening w glucagon and insulin levels in the fasting state to maintain glucose levels

glucagon inc, insulin dec

during the fasting state, most (75%) of glucose disposal occurs in…

insulin independent tissues: brain, splanchnic area- liver and GI

during the fasting state, the rest (25%) of glucose disposal occurs in…

insulin dependent tissues: muscles

during a fasting state, your body is getting endogenous production of glucose… through what processes

50% glucogenogenesis and 50% glycogenolysis

what is gluconeogenesis

process of making glucose from amino acids

what is glycolysis

process of breaking down glucose to use for energy

what happens when glycogen stores are depleted

• TG are broken down to FFA and glycerol → ketone bodies and glucose

• protein catabolism through the process of gluconeogenesis

what is glucagon secreted from

pancreatic alpha cells

if there is a low glucose level in the blood, what is the process of glucagon secretion

hypoglycemia → dec ATP → ATP-sensitive K channels close → intracellular K rises; depolarizes → Ca influx into the cell → glucagon released

what is the action of glucagon in the body

• inc glycolysis

• in lipolysis → FFA generated

• ketone formation

• inc gluconeogenesis

what is hypoglycemia

when plasma glucose levels drop below normal range: <55 mg/dL OR <70 mg/dL

what can cause hypoglycemia

• inc in insulin due to exo or endogenous causes

• dec in counter-regulatory hormones

what are the types of symptoms someone can experience from hypoglycemia

• adrenergic/cholinergic: ~ 58 mg/dL

• neuroglycopenic: 49-51 mg/dL

what are some adrenergic/cholinergic symptoms a pt can experience from hypoglycemia

sweating, warmth, anxiety, tremor, nausea, palpitations. tachycardia, hunger

what are some neuroglycopenic symptoms a pt can experience from hypoglycemia

behavioral changes, changes in vision/speech, confusion, seizure, etc etc…

what are some causes of non-insulin mediated hypoglycemia

• alcohol

• severe illness

• malnutrition

• kidney or liver failure

• insulinoma

• rare tumors that secrete IGF

explain how alcohol is a cause of non-insulin mediated hypoglycemia

impairs gluconeogenesis

explain how severe illness can be a cause of non-insulin mediated hypoglycemia

glucose consumption will outpace production

explain how malnutrition is a cause of non-insulin mediated hypoglycemia

inadequate substrate for gluconeogenesis

explain how kidney or liver failure is a cause of non-insulin mediated hypoglycemia

impaired gluconeogenesis

what organs carry out gluconeogenesis

kidney or liver

what is insulinoma

insulin secreting tumors of pancreatic origin (beta cells) → will secrete insulin regardless of glucose status → leads to recurrent fasting hypoglycemia

what are the insulin deficiencies that can lead to hyperglycemia

dec in insulin

• absolute deficiency- T1D

• relative deficiency- insulin resistance, T2D

what is glucagonoma

tumor of pancreatic alpha cells; will produce glucagon regardless of glucose levels

what are the symptoms of a gluconoma

classical clinical triad

• hyperglycemia

• weight loss

• necrolytic migratory erythema

what is somatostatinoma

somatostatin secreting tumor of the D-cells of the pancreas, inhibits insulin release as well as other hormones

what are the symptoms of somatostatinoma

classical clinical triad

• diarrhea

• hyperglycemia

• cholelithiasis

what are other (3) endocrine abnormalities that can cause hyperglycemia

• acromegaly- due to elevated growth hormone

• cushing syndrome- due to elevated cortisol

• pheochromocytoma- due to elevated metanephrines

what is diabetes mellitus

fasting or post-meal hyperglycemia due to absolute or relative insulin deficiency

what are the types of diabetes mellitus

• type 1: absolute deficiency

• type 2: relative insulin deficiency due to insulin resistance

• other: MODY, pancreatic diabetes

what is the etiology of type 1 diabetes

beta cells are destroyed- autoimmune condition

etiology of type 2 diabetes

insulin resistance; polygenic disease w a strong familial component

what is the onset of symptoms in type 1 diabetes

peak age of presentation during adolescence- typically abrupt onset of symptoms

what is the onset of symptoms in type 2 diabetes

gradual onset

tx for type 1 diabetes

insulin required for survival

tx for type 2 diabetes

many pharmacological options available

what are the 3 types of insulin resistance

• pre-receptor defects

• receptor defects

• post-receptor defects

what are some classic symptoms of diabetes mellitus

polydipsia, polydisphagia, polyuria, weight loss

what are some tests that can be used to dx diabetes mellitus

• symptomatic

  • hyperglycemia w BG >/= 200 mg/dL

• asymptomatic

  • HbA1c

  • fasting plasma glucose

  • oral glucose tolerance test

what is HbA1c

is a form of hemoglobin modified by exposure to glucose; how the risk of microvascular and macrovascular complications is related to glycemia

the higher the HbA1C…

the higher the ave glucose values over the prior 3 mo

what is pre-diabetes

this is present before T2DM is present

how to dx pre-diabetes

• impaired fasting glucose (IFG)

• impaired glucose tolerance (IGT)

• A1C

what are the criteria for metabolic syndrome

• waist circumference: vary among location

• TG: >/= 150 mg/dL

• HDL-C: M <40 and F < 50 mg/dL

• BP: >/= 130 / >/= 85

• fasting glucose: >/= 100 mg/dL

what is the underlying defect in the metabolic syndrome

insulin resistance plays a major role: inc FA leads to inc inflammation → worsen insulin resistance and impair insulin signaling; abnormal adipokine profile

what is the % of adults in the US who are over 65 and have type 2 diabetes

• inc w age

• 26.8% among >/= 65 yrs

what are the clinical features of T2 diabetes (6)

• strong family history

• polyuria, polydispia

• frequent UTIs and genital yeast infections

• sometimes advanced complications

• DKA not typically present

• HHS- hyperosmolar hyperglycemia syndrome

what are GLP-1 and GIP

are both incretin hormones that stimulate the release of insulin from the pancreas → essential for regulating post-prandial blood sugar

recall: generally, how does insulin act to store energy

• will lead to glucose uptake into cells via translocation of the GLUT4 transporter

• promotes glycogen synthesis in liver and skeletal muscle while inhibiting stored glycogen breakdown

• dec hepatic glucose output by inhibiting gluconeogenesis

• inhibits lipolysis

• promotes TG storage

recall: in the fasted state, insulin dec and glucagon inc, what effect does glucagon have

• mobilizes stored liver glycogen

• stimulates glycogenolysis to inc hepatic glucose output

• stimulates amino acid uptake for glucogenogenesis