All Things Diabetes/Hypoglycemia (Pales + Darrow) Flashcards
granuloma annulare
blister/circular ring/rash assoc. w/ diabetes, thyroid disease, infections, etc.
- type IV reaction w/ granulomas and NO scaling
findings of metabolic syndrome?
2 physical:
- Waist: >40 inches men, >35 inches women
- HTN > 130/85
3 lab findings:
- Triglycerides >150 mg/dL
- HDL-C 100 mg/dL
NOTE: apple body is worse
Also have: hyperuricemia, hyperdense LDL, increased plasminogen inhibitor, increased platelet adhesion, increased homocysteine
adipokines
= inflamm. immune mediators that are secreted by adipose tissue
Dysregulation of adipokine secretion, free fatty acid toxicity, macrophage infiltration, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating the insulin resistance, increased risk of diabetes, and cardiovascular disease in the metabolic syndrome.
other mediators:
leptin, abnormal adiponectin, resistin, visaftin, TNFalpha, IL-6, thrombospondin
changes in adipose tissue w/ obesity?
lean subjects:
- adipose has few macrophages
- secretes high levels of adiponectin, low levels of inflamm. cytokines
- beta oxid. of lipids is high
- little ectopic fat in mm. and liver
obesity:
- adipose contains many macrophages
- high levels of adipokines
- low levels adiponectin
- fat is expandable and there is ectopic lipids everywhere (may result from tx with TZD)
action of TZD’s in regards to fat?
activate PPAR
- decreased insulin resistance
- leptin levels decreased
- decreased interleukin levels
- adipocyte differentiation is modified: see increased adiponectin and expandable fat
can cause hypoglycemia, weight gain, along with CHF/MI - use is controversial
atherogenesis of DM?
hyperglycemia, xs FFA’s and insulin resistance –> cause hyperglycemia mediated mitochondrial superoxide production
results in:
- vasoconstriction: HTN
- inflammation: release of cytokines
- thrombosis: hypercoagulable state
diagnosis of type II DM?
- Random glucose > 200 mg/dL with compatible symptoms
- FBS > 126 mg/dL x 2 (prediabetes = 100-125 mg/dL)
- 2 hour post meal > 200 mg/dL x 2 (Prediabetes = 140 - 199 mg/dL)
- HbA1c > 6.5% x 2 (Prediabetes 5.7 – 6.4%) – falsely low with HB F, hemolytic anemia, acute bleed, vitamins C and E.
what causes type II DM?
- Genetic: TCF7L2 (transcription factor 7 like 2 - member of WNT signal pathways) - results in early beta cell fatigue and death
- environmental: visceral obesity (increased resistin, TNF-alpha, IL6) - results in insulin resistance
what causes polyuria?
(C)- dripped
- cortisol excess
- DM
- recovery from renal failure (urea)
- ions: hyper ca2+ hypo K (channels not responding to ADH)
- parkinson’s
- psychogenic polydipsia
- enzyme: vasopressinase
- drugs: lithium, demeclocycline, methicillin
antibodies of DM type 1? HLA type?
- Glutamic acid decarboxylase 65 (GAD 65) antibodies
- Insulin antibodies (IAA)
- Islet cell cytoplasmic antibodies (ICA)
- Insulinoma-associated-2 autoantibodies
- Zinc transporter antibodies (Abs)
HLA-DR3, DR4
maternity onset diabetes of youth (MODY) - why is it not type 1 or type 2?
- have abnormal nuclear transcription factors in Beta cells
why not type 1?
- strong family hx
- no ketoacidosis when off insulin
- no pancreatic autoantibodies
- has detectable C-peptide levels
why not type 2?
- unusual to have onset <25 y/o
- not obese
- have high HDL levels (lack of apo M d/t decreased TFHNF1)
apo M and MODY?
in MODY there is a defect in TFHNF 1 (transcription factor hepatic nuclear factor) resulting in decreased
apo M and thus decreased clearance of HDL, which in this case is not cardioprotective.
** this is NOT the case in DM II where see decreased levels of HDL
MODY syndromes have impaired glucose induced secretion of insulin
how is MODY different from type 2 DM?
type 2 DM:
- polygenic inheritence
- usually >40 years
- usually obese, w/ metabolic syndrome
MODY:
- monogenic, autosomal dominant inheritance
- usually <25 y/o
- usually seen across generations
- non-obese, no metabolic syndrome
what is MODY?
several hereditary forms of diabetes caused by mutations in an autosomal dominant gene : resulting in ineffective insulin production or release by beta cells
- have very strong family hx, d/t autosomal dominant pattern
- have mild/moderate hyperglycemia discovered before age 30
- first degree relative w/ DM
- absence of positive antibodies
- have low insulin
- absence of obesity
Type 3 is most common:
- Mutations of the transcription factor HNF1α gene (a homeobox gene). 30%–70% cases.
- Tend to be responsive to sulfonylureas. Low renal threshold for glucose.
reasons for insulin resistance and poorly controlled diabetes?
AEIOU has poorly controlled Diabetes
- Aging
- Endocrine disorders: (cushing, acromegaly, pheo)
- infections: dental, sinus
- obesity
- uremia and hepatic disease (hemochromatosis)
- acanthosis nigricans
- stress
- pregnancy, pancreatic disorders
- cortisone
- disorders of insulin
drugs producing hyperglycemia?
- beta blockers
- glucocorticoids
- alcohol
- statins
- thiazides
- oral contraceptives
- pentamide
- niacin
why is there insulin resistance in fat, mm, liver?
TNF alpha - this same mechanism causes both insulin resistance and eventually ends up killing beta cells –> resulting in insulin deficiency
skin manifestation of diabetes/hyperglycemia?
- eruptive xanthomas
= familial hypertriglyceridemia w/ hepatic overproduction of VLDL (Type IV) may be acquired in diabetes - complication: pancreatitis
- Type IV (HDL deficiency) can also be associated with Type I (increased chylomicrons- hyperchylomicronemia) resulting in Type V (familial mixed hypertriglyceridemia) - where LPL activity is decreased
cheriopathy
Hyperglycemia results in glucotoxicity which results
in oxidative stress –> results in tissues in hands becoming rigid and pt. can’t approximate fingers d/t fibrosis
CAD equivalents?
need to give a statin!
LDL >190
- DM
- cerebral arterial disease
- aortic aneurysm
- PVD or MI/stroke risk
Acquired Type IIb Hyperlipidemia
Familial Combined Hyperlipidemia
- Increased hepatic secretion of Apo B 100 and VLDL (increased triglycerides and cholesterol – can differentiate from Type III with phenotype E2/E2 and broad beta band versus increased ApoB, plus in type III, Chol and Trig are equal).
- Common, often hypertensive and obese, no xanthomas, early CAD, PVD, stroke.
- Acquired type in Diabetics.
- Most common cause of lactescent plasma.
Insulinoma signs?
- sudden weight gain and emotional illness
Whipple’s triad:
- low blood glucose
- mental sx induced by fasting/exercise
- sx relieved by intravenous glucose
- if serum C-peptide is high (pro-insulin), think insulinoma
- typical benign endocrine tumor histology
Whipple’s triad
indicates insulinoma
- Symptoms and signs of hypoglycemia
- Low glucose at the time of the event (< 50 mg/dL)
- Reversal with correction of the hypoglycemia: give patient sugar and they feel better
presentation of hypoglycemia?
Sympathoadrenal signs (glucose < 60 mg/dL) = sweating, tachycardia, tachypnea, anxiety, tremulousness, and nausea. More common in post prandial (PP) hypoglycemia.
***Neuroglycopenic signs (glucose < 50 mg/dL) = blurred vision, fatigue, dizziness, headache, confusion, seizures, coma, death. More common in fasting hypoglycemia. (these dominate)
how to ddx insulinoma?
- Reconfirm finger stick with serum glucose
- Draw serum insulin and C-peptide – when glucose is below 50 mg/dL, the serum insulin level should be less than 5 μU/mL (fasting range 5-20 μU/mL). The C-peptide will separate out the exogenous from endogenous sources.
- Fast up to 72 hours with simultaneous glucose and insulin (proinsulin and C-peptide can also be drawn if needed)
- Consider doing serum β-hydroxybutyrate level which will be low if insulin is a cause of the hypoglycemia, ie in the presence of insulin the β-hydroxybuterate will be below 2.7 mg/dL.
when see insulinoma what else do you look for?
hyperparathyroidism and pituitary adenoma
insulinomas
- 80% are benign pancreatic adenomas, while 10% are multiple,
- 5% are carcinomas
- 5% are MENs (Screen with serum calcium and prolactin).
tx for insulinomas?
- Surgery
- Frequent feedings
- Diazoxide (opens up K+ channel, prevents depolarization, inhibits insulin release)
- Verapamil (CCB - inhibits calcium influx and keeps insulin from being secreted)
- Octreotide
how do you differentiate b/w exogenous and endogenous hyperinsulinemia?
C-peptide (if present, indicates endogenous)
- if absent = too much insulin injections
nurse, low glucose, normal/elevated insulin w/ C-peptide present - what do you think?
taking insulin promoting drug: serum sulfonylurea level will be high (results in hypoglycemia)
