Other DM, MODY

Question 1

Ex of disease of the exocrine pancreas causing 2ary diabetes

Answer 1

Pancreatitis
Trauma, pancreateomy
Neoplasia
Cystic Fibrosis
Hemochromatosis
Fibrocalculous pancreatopathy

Question 2

criteria for mody

Answer 2

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

Question 3

MODY 1:
- gene
- mutated protein

Answer 3

• HNF4A
• Hepatocyte nuclear factor-4a
  Found in liver and ß cells

Question 4

MODY 1
clinical presentation, natural history

Answer 4

Progressive ß cell function declines -> eventually develop chronic diabetes complications
Do better with insulin therapy
Rarest of all MODYs
Impaired renal absorption - glucosuria

Question 5

MODY 2:
- gene
- mutated protein

Answer 5

• 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

Question 6

MODY 2
clinical presentation, natural history

Answer 6

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

Question 7

MODY 3:
- gene
- mutated protein

Answer 7

• HNF1A
• Hepatocyte nuclear factor-4a
  Found in liver and ß cells

Question 8

MODY 3
clinical presentation, natural history

Answer 8

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

Question 9

MODY 4:
- gene
- mutated protein

Answer 9

PDX1

Pancreatic duodenal homeobox-1
Mediates insulin gene transcription and regulates expression of other ß cell-specific genes (incl. GCK)

Question 10

MODY 4
clinical presentation, natural history

Answer 10

If both allele non-functional – agenesis of entire pancreas
If heterozygous – mild MODY, usually later onset (mean age 35yo)

Question 11

MODY 5:
- gene
- mutated protein

Answer 11

HNF1B

Hepatocyte nuclear factor-1ß
Expressed early in development of the liver, pancreas, kidneys, and GU
Not found in mature ß cells

Question 12

MODY 5
clinical presentation, natural history

Answer 12

Moderately severe MODY  progression to insulin and severe diabetic complications
These mutations also frequently cause reduction in overall size of pancreas, decrease insulin production, and congenital defects in kidney and GU tract
Patients can also have varying degrees of cholestatic jaundice, hyperuricemia, nephropathy, and hypomagnesemia (renal Mg wasting)

Question 13

Definition of neonatal diabetes

Answer 13

diabetes diagnosed before 6 months of age

Question 14

Presentation of neonatal diabetes

Answer 14

decreased birth weight (IUGR) and decreased fat stores in addition to hyperglycemia

reduced circulating insulin and C-peptide levels

Question 15

how often is neonatal diabetes transient?

Answer 15

50%