Table 2.7

Most common causes of monogenic diabetes (68)

GeneInheritanceClinical features
MODY
GCKADGCK-MODY: stable, nonprogressive elevated fasting blood glucose; typically does not require treatment; microvascular complications are rare; small rise in 2-h PG level on OGTT (<54 mg/dL [3 mmol/L])
HNF1AADHNF1A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; lowered renal threshold for glucosuria; large rise in 2-h PG level on OGTT (>90 mg/dL [5 mmol/L]); sensitive to sulfonylureas
HNF4AADHNF4A-MODY: progressive insulin secretory defect with presentation in adolescence or early adulthood; may have large birth weight and transient neonatal hypoglycemia; sensitive to sulfonylureas
HNF1BADHNF1B-MODY: developmental renal disease (typically cystic); genitourinary abnormalities; atrophy of the pancreas; hyperuricemia; gout
Neonatal diabetes
KCNJ11ADPermanent or transient: IUGR; possible developmental delay and seizures; responsive to sulfonylureas
INSADPermanent: IUGR; insulin requiring
ABCC8ADTransient or permanent: IUGR; rarely developmental delay; responsive to sulfonylureas
6q24 (PLAGL1, HYMA1)AD for paternal duplicationsTransient: IUGR; macroglossia; umbilical hernia; mechanisms include UPD6, paternal duplication or maternal methylation defect; may be treatable with medications other than insulin
GATA6ADPermanent: pancreatic hypoplasia; cardiac malformations; pancreatic exocrine insufficiency; insulin requiring
EIF2AK3ARPermanent: Wolcott-Rallison syndrome: epiphyseal dysplasia; pancreatic exocrine insufficiency; insulin requiring
FOXP3X-linkedPermanent: immunodysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome: autoimmune diabetes; autoimmune thyroid disease; exfoliative dermatitis; insulin requiring
  • AD, autosomal dominant; AR, autosomal recessive; IUGR, intrauterine growth restriction.