B5.001 - Big Case DM2 Flashcards
What is acanthosis nigricans
a common condition characterized by velvety, hyperpigmented plaques on skin. Esp. neck and axillae
pathophys of acanthosis nigricans
insulin resistance and hyperinsulinemia plays a role in the development of acanthosis nirgricans. Elevated levels of insulin may stimulate keratinocyte and dermal fibroblast proliferation via interaction with IGFR1 resulting in the plaque like lesions that typify the disorder
recommendations for diabetes screening
beginning at 45 at least every 3 years
screen more frequently if BMI >25 and person has 1 other risk factor
risk factors for diabetes
family Hx (1st degree relative) High risk race history of gestational diabetes or delivery of baby >9lb polycystic ovary syndrome HTN HDL <35, TG >250 Hx of CVD sedintary
normal HbA1c, IFG or IGT, T2DM
normal <5.7
IFG or IGT 5.7-6.4
T2DM >6.5
fasting plasma glucose level
normal
IFG or IGT
T2DM
normal <100
IFG or IGT 100-125
T2DM >126
OGTT normal, IFG/IGT, T2Dm
normal <140
IFG/IGT 140-199
T2DM >200
what is the best way to prevent progression to T2DM
Lifestyle changes
what are the 3 major components of progression to T2DM
Impaired incretin action
insulin resistance
relative insulin deficiency
describe the general role of obesity in development of insulin resistance
abdominal adipose tissue is more metabolically active than subcutaneous fat
increased release of FFA, TNF-alpha and resistin leading to proinflammatory state and insulin resistance
definition of metabolic syndrome
abdominal obesity, waist circumference >40, women >35 TGs >150 HDL-C <40, <50 blood pressure >135/85 fasting glucose >100
role of beta cells in T2DM
reduction in number of Bcells
pancreas cant renew B cells after 30 yo
glucolipotoxicity and amyloid deposition result in B cell apoptosis through oxidative and endoplasmic reticulum stress
describe the role of alpha cells in T2DM
abnormal glucagon released by alpha cells
elevated fasting glucose
non suppression after meal ingestion
how does sympathetic and parasympathetic NS control glucose metabolism
directly through neuronal input
indirectly through circulation to affect release of insulin and glucagon and production of hepatic glucose
other than SYM and PARA what affects glucose metabolism
vagus nerve
hypothalamus
what is C peptide
a peptide made along with insulin, more stable than insulin so a better marker for insulin production
what does incretin do
a substance that stimulates insulin secretion
released by gut in response to food
what are 2 incretins
GLP-1
GIP
what happens to incretins in T2DM
plasma levels of GLP-1 are diminished
the contributes to rise in plasma glucagon secretion and impaired suppression of hepatic glucose production that occurs after a meal
GIP less able to stimulate glucose dependent insulin secretion
role of alpha cells in T2DM
elevated secretion of glucagon
leads to markedly increased rate of hepatic glucose production
possible liver HS to stimulatory effect of glucagon in hepatic gluconeogenesis
role of GLP-1 in liver, brain, pancreas, stomach, beta cell
liver - less glucagon = less hepatic glucose output
brain - promotes satiety and reduction of appetite
pancreas - alpha cell decreases post meal glucagon secretion
stomach - slows gastric emptying
beta cell - increases insulin secretion
what degrades GLP-1
DDP-4
what is DDP-4
ubiquitous serine protease
high levels in lumen of intestine, liver, lung, kidney
membrane bound and free circulating form
degrades GLP-1, GIP
what type of cell expresses DPP-4
on surface of T cells, T cell activation and other immunological responses
