pathophys of type 2 diabetes Flashcards
define pre-diabetes
Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG). Diagnosed by one of the following: HbA1c 5.7-6.4, fasting plasma glucose (FPG) levels 100 -125 mg/dL, or 2 hr values on the oral glucose tolerance test (OGTT) of 140- 199 mg/dL
treatment/prevention of diabetes in pre-diabetic patients
5–10% loss of body weight, exercise (150 minutes/week), and metformin. Plus yearly screening for diabetes and CVD risk profile
list values for normal fasting glucose, impaired fasting glucose, and diabetic fasting glucose
Normal: 126mg/dl
list values for normal glucose tolerance, impaired glucose tolerance and diabetic glucose tolerance
2 hr post glucose- normal: 200mg/dl
List values for normal, pre-diabetic and diabetic A1C
normal: 6.5
diagnosis of diabetes
elevated A1C OR fasting plasma glucose OR glucose tolerance test
When are pregnant women screened for gestational diabetes
If average risk, at 24-28 weeks. If high risk (obesity, history, glycosuria, family history), as soon as feasible then again at 24-28 weeks.
compare glucose tolerance test in gestational diabetes to type 2 diabetes
Gestational diabetes: oral glucose load of 100g. Type 2: 75 g glucose
pathogenesis of type 2 diabetes
Decreased insulin sensitivity (insulin resistance) followed by inability of beta cells to compensate for defects in insulin action, thus failing to secrete enough insulin
define insulin resistance
Inadequate biological effects of insulin to stimulate glucose uptake in the skeletal muscle glucose and to suppress endogenous glucose production by the liver
genetics of T2D
Very family oriented- 38% of siblings and 1/3 of offspring, 90-100% in monozygotic twins. NOT associated with any particular HLA gene types
environmental factors of T2D
sedentary lifestyle and obesity
describe insulin secretion in T2D
At first, normal or elevated insulin. Then, acute Insulin release in response to IV is glucose it lost, but prolonged response is preserved/exaggerated. Acute insulin release in response to non-glucose stimuli (amino acids) is normal, suggesting specific defect in glucoregulation.
When is insulin required in most T2D patients
After 10 years, insulin secretion is diminished and insulin is necessary for control
Prevention of insulin requirement in T2D
Aggressive normalization of blood glucose in early diabetes has shown long term effects on diabetes complications. Prolonged hyperglycemia produces glucose toxicity where insulin secretory capacity is impaired
describe insulin resistance in T2D
Hepatic insulin resistance results in loss of insulin suppression of hepatic glucose output (fasting hyperglycemia). Insulin resistance in the skeletal muscle and fat leads to defects in insulin-mediated storage of glucose and, fat and protein (postprandial hyperglycemia)
what is metabolic syndrome
aka insulin resistance syndrome- associated with T2D. Manifests as central obesity, glucose intolerance, hypertension, atherosclerosis, polycystic ovary syndrome
biochemical manifestations of metabolic syndrome
altered carbohydrate metabolism, dyslipidemia, procoagulant state
what is maturity onset diabetes of youth
Presents early in life with negative antibody screens and strong family history. May be due to glucokinase deficiency (MODY2). Impaired insulin secretion with minimal/no defects in insulin action. Autosomal dominant
what is diabetic ketoacidosis
severe insulin deficiency leading to extreme hyperglycemia (usually glucose >300mg/dl), an increased anion gap metabolic acidosis (usually pH 5 mM).
insulin and glucagon effect on lipolysis, ketogenesis, gluconeogenesis, glycogenesis, glycogenolysis and glycemia
insulin: dec, dec, dec, incr, dec, dec. Glucagon: inc, incr, incr, dec, incr, incr
pathogenesis of diabetic ketoacidosis
lack of insulin/ elevated catecholamines > lipolysis >FA delivered to liver > ketogenesis in liver > acidosis. ALSO hyperglycemia > glycosuria/polyuria > osmotic diuresis (loss of electrolytes and fluid) >dehydration > decreased renal blood flow > decreased GFR reduces kidney’s ability to excrete glucose and hyperosmolarity worsens >acidosis
anion gap calculation
Na-Cl-bicarb
Signs of DKA
altered mental state, (40% concious, 40% drowsy, 20% comatose), dehydration, postural hypotension, tachycardia
precipitating cause of DKA
The most common cause of DKA overall is infection often accompanied by misguided omission of insulin
diagnosing DKA
serum glucose >200mg/dl, urinary ketones, serum beta-hydroxybutyrate
DKA treatment
insulin (inhibit gluconeogenesis and ketogenesis), fluid replacement (improve circulation and perfusion)
who gets DKA
usually type 1 diabetes
most common acute complication of diabetes
hypoglycemia
define hypoglycemia
plasma glucose <60mg/dl
hypoglycemia symptoms
adrenergic (excessive secretion of epi): sweating, tremor, tachycardia, anxiety. Neuroglycopenic (dysfunction of CNS): confusion, convulsions, loss of conciousness, dizziness, headaches
who gets hypoglycemia
Hypoglycemia is about 2-3 time more common in patients trying to normalize blood glucose with intensive insulin regimens ie. type 1 diabets
what controls hypoglycemia in diabetes
Glucagon stimulates glycogenolysis in liver/release of glucose and epi stimulates glycogenolysis. After a variable duration of diabetes, glucagon responsiveness to hypoglycemia is lost and epinephrine becomes the primary defense against hypoglycemia. Epinephrine can be blunted in recurrent hypoglycemia. Cortisol and growth hormone also raise blood glucose, but do so much more slowly.
what is hypoglycemia unawareness
patient no longer has the adrenergic warning signs of diabetes and may go into an altered mental state with no warning symptoms at all. This is more common in patients who have frequent hypoglycemia
treatment of hypoglycemia unawareness
avoid hypoglycemia for 3 weeks or more
Ddx of hypoglycemia
drugs (insulin, sulphonylureas), ethanol, adrenal insufficiency, renal failure (most common in T1D), insulinoma
