MODY + NDM Flashcards
Meds that can cause hypoBg
Insulin
Sulfonylurea
Fluoroquinolones
Pentamidine
Beta-blockers
ACEi
Ethanol
Salicylates
Risk factors for adverse cardiopulmonary symptoms (ie, pulmonary hypertension) with diazoxide treatment
●Respiratory distress and/or bronchopulmonary dysplasia
●Pulmonary hypertension
●Cardiomyopathy
●Structural heart disease
●Prematurity
●Small for gestational age
●Infant of a diabetic mother
●Post discharge residence at high altitude
when to suspect monogenic diabetes
-Age <6 months
-Only mild hyperglycemia
-Family history in an autosomal dominant fashion
-No complications (not in guidelines)
-Low insulin requirements if any (<0.5U/kg/day)
-Family or personal hx of neonatal diabetes
-Normal BMI and no clinical sx of insulin resistance
- No acanthosis nigricans or signs of insulin resistance
types of cells in pancreas and what they do
A-cell (alpha): Glucagon
- Raises blood glucose
B-cell (beta): Insulin
- Lowers blood glucose
D-cell (delta): Somatostatin
- Inhibits alpha and beta cells (caps against extremes of glucose)
PP-cell: Pancreatic polypeptide
- Levels rise in response to hypoglycemia and in fasting; may enhance insulin sensitivity
Ex of disease of the exocrine pancreas causing 2ary diabetes
Pancreatitis
Trauma, pancreateomy
Neoplasia
Cystic Fibrosis
Hemochromatosis
Fibrocalculous pancreatopathy
criteria for MODY dx
Dominant inheritance with at least two (and preferably three) consecutive affected generations
Onset before age 25 to 30 years
Evidence of significant but impaired residual insulin secretion reflected in C-peptide levels whether or not the patient is being treated with insulin
MODY 1:
- gene
- mutated protein
- HNF4A
- Hepatocyte nuclear factor-4a
Found in liver and ß cells - in NUCLEUS
MODY 1
age, clinical presentation, natural history
renal threshold glucosuria
tx
teenager age/young adult
PP hyperBG -> general hyperBG
Progressive ß cell function declines -> eventually develop chronic diabetes complications
low renal threshold glucosuria
Do better with insulin therapy
MODY 2:
- gene
- mutated protein
- GCK
- Glucokinase
Control rate-limiting step in glycolysis
Determines rate of ATP production from glucose and insulin secretory response to glucose
Reduced GCK activity resets sensitivity of ß cell so a higher BG level is needed to stimulate insulin secretion
MODY 2
clinical presentation, natural history
Fasting hyperglycemia and mild diabetes
If only one mutated GCK allele – benign course with few or no chronic complications
Respond well to diet therapy or oral antidiabetic drugs without needing insulin
If homozygote – permanent neonatal diabetes
MODY 3:
- gene
- mutated protein
- HNF1A
- Hepatocyte nuclear factor-4a
Found in liver and ß cells
MODY 3
clinical presentation, natural history
Most common in Europeans
Progressive ß cell function declines -> high rates of microvascular complications
Eventually dependence on insulin
Also often have reduced CRP
Early in course of disease, may have exaggerated response to sulfonylureas
MODY 4:
- gene
- mutated protein
PDX1
Pancreatic duodenal homeobox-1
Mediates insulin gene transcription and regulates expression of other ß cell-specific genes (incl. GCK)
MODY 4
clinical presentation, natural history
If both allele non-functional – agenesis of entire pancreas
If heterozygous – mild MODY, usually later onset (mean age 35yo)
MODY 5:
- gene
- mutated protein
HNF1B
Hepatocyte nuclear factor-1ß
Expressed early in development of the liver, pancreas, kidneys, and GU
Not found in mature ß cells
