B5-002 Diabetes Mellitus Metabolism Flashcards
core defects of type 2 diabetes
2
- insulin resistance
- B cell dysfunction
translocates to the cell membrane to take up glucose
GLUT4
what 2 stimuli cause translocation of GLUT4 in muscle?
insulin
muscle contraction
in a healthy condition, insulin and muscle contraction have an […] effect on glucose transport
additive
in an insulin resistance individual, insulin and muscle contraction have a […] effect on glucose transport
synergistic
farmers requiring less glucose then sedentary workers
hepatic insulin resistance is commonly linked to
fatty liver
insulin binds receptors on hepatocytes to turn off
gluconeogenesis
lipids in the liver cells are thought to prevent insulin from “turning off” […] in fatty liver
gluconeogenesis
hepatic glucose production is […] in DM 2 patients
elevated
dysregulation of […] plays a prominent role in DM 2 pathology
hepatic glucose production
critical locations for post prandial glucose disposal in DM2
2
skeletal muscle
liver
hepatic glucose uptake is […] in DM 2
suppressed
what contibutes to elevated postprandial glucose in DM2 patients?
HGP is not suppressed to the same degree as a healthy control
dysregulated hepatic glucose metabolism contributes to:
2
elevated fasting glucose
elevated post prandial glucose
as insulin sensitivity decreases, […] increases to compensate
beta cell insulin production
when beta cells are no longer able to compensate, this causes
DM 2 or
impaired glucose tolerance
primary genetic component of DM 2
beta cell ability to compensate
post prandial glucose exursions are tightly linked to
CVD risk
higher glucose post […] is linked to higher CAD risk
2 hr OGTT
swings in glucose in circulation cause […] in various tissues
oxidative stress
why might it be important to do both a fasting glucose and 2 hr OGTT?
impaired fasting glucose and impaired glucose tolerance can occur separately
[…] should lead to the highest glucose responses to a meal or OGTT
combined IFG/IGT
GLP-1 levels are […] in patients with DM 2
decreased
either reduced production or increased DPP4 breakdown
L cells produce
2
GLP-1
GIP
incretins
why is C reative protein used as a marker of insulin production?
it is more stable than insulin
GLP-1 induced insulin secretion is […] in DM2
reduced
isoglycemic infusion of glucose stimulated insulin normally in DM2 patients. This suggests….
incretins (GLP, GIP) are critical for normal insulin response
[…] levels are much higher in the portal vein than in systemic circulation
insulin
the pancreas dumps insulin and glucagon into the […]
portal vein
the liver takes up […] of insulin, lowering what is seen in systemic circulation
50-85%
insulin degrading enzyme
insulin injections cannot mimic
high insulin levels in portal vein
most adequate therapy for controlling hepatic glucose production and hepatic glucose storage
combination pre-meal and post-meal insulin
in most patients [….] goes up over time despite use of anti-hypeglycemic agents
HbA1C
lifestyle interventions are critical
greater than […] of walking a day dramatically lowers the risk of DM2
21 min
[…] steps/day confers a level of protection against DM2
3,500
most powerful regulation of insulin sensitivity
daily activity
both standing and light activity even 20 min lowers
glucose and insulin
improves insulin sensitivity
impaired fasting glucose is believed to be driven by
increased hepatic glucose production
impaired glucose tolerance is attributed to
impaired glucose uptake
most powerful risk factors for development of DM2
5
- obesity
- physical inactivity
- genetics
- ethnicity
- age
ingested glucose stimulates L cells to produce
GLP-1
signals pancreatic beta cells to produce greater insulin levels during postprandial conditions
GLP-1
[….] is integral for a higher insulin response in post prandial conditions
GLP-1 production and glucose sensing
thats why lower response for IV vs oral
DM2 patients with supressed GLP-1 responses have impaired […] response
insulin
primary cause of fatty liver
obesity
increased transaminases and elevated fasting glucose may indicate
fatty liver
glucose levels > 200 two hours after OGTT test, but a normal A1C is caused by
glucose intolerance
stimulates pancreatic beta cell insulin production
GLP-1
association between “insulin sensitivity” and “beta cell insulin secretion in response to glucose”
disposition index
exercise is most effective at improving beta cell insulin production in individuals who are
early in their prognosis and have lower HbA1C
what patients would be least responsive to effects of exercise?
individuals who have had diabetes for prolonged period of time or have very high HbA1C
postprandial surges in glucose or large swings are more tightly linked to
oxidative stress –> CVD risk
