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youth-onset type 2 diabetes; mature onset diabetes of the young (MODY)

Epidemiology: - incidence on the rise - from 1999 to 2008, prevalence of diabetes or prediabetes, measured by a single fasting blood glucose above the upper limit of normal, increased from 9% to 23% Pathology: - primary defect in insulin secretion - delayed insulin response to glucose Genetics: 1) autosomal dominant inheritance [15] 2) associated with defects in HNF4A (MODY1) [8] 3) mutation in the gene for glucokinase (MODY2) (60%) [9] 4) associated with defects in HNF1A (MODY3) [6] 5) associated with defects in PDX1 (MODY4) [7] 6) associated with defects in HNF1B (MODY5) [5] 7) associated with defects in NEUROD1 (MODY6) [4] 8) associated with defects in KLF11 (MODY7) [11] 9) associated with defects in CEL (MODY8) [10] 10) associated with defects in PAX4 (MODY9) [12] 11) associated with defects in the insulin gene (MODY10) [13] 12) associated with defects in BLK (MODY11) [14] Clinical manifestations: - onset in childhood or early adulthood (10-45 years), usually before 25 years of age) - strong family history or diabetes mellitus - lean body type - no acanthosis nigricans or features of Cushing syndrome - major hyperglycemia associated with microvascular complications Laboratory: - C-peptide in serum is normal - HNF1A gene mutation - HNF1B gene mutation - HNF4A gene mutation Complications: - higher incidence of complications than type 1 diabetes - diabetic nephropathy (RR=2.6), albuminuria moderate (55%)* - diabetic retinopathy (RR=2.2), - mostly mild (50%)* - diabetic neuropathy (RR=2.5), (32%)* - obesity (mean BMI 36 kg/m2)* - dsylipidemia (50%)* - hypertension (67%)* - myocardial infarction (4/700), stroke (4/700), heart failure (6/700)* * 13 years since initial diagnosis, mean age 26 years [18] Management: - dietary & lifestyle measures - metformin is initial drug of choice - addition of glitazone may be helpful - long-acting insulin may be necessary in > 1/3 of patients [3]

Interactions

disease interactions

General

diabetes mellitus type 2 (insulin-resistant) genetic disease of the endocrine system

Database Correlations

OMIM correlations

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 18 American College of Physicians, Philadelphia 1998, 2006, 2018.
  2. OMIM :accession 606391
  3. TODAY Study Group A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes N Engl J Med, April 29, 2012 PMID: 22540912 http://www.nejm.org/doi/full/10.1056/NEJMoa1109333 - Allen DB TODAY - A Stark Glimpse of Tomorrow N Engl J Med, April 29, 2012 PMID: 22540913 http://www.nejm.org/doi/full/10.1056/NEJMe1204710
  4. OMIM :accession 606394
  5. OMIM :accession 137920
  6. OMIM :accession 600496
  7. OMIM :accession 606392
  8. OMIM :accession 125850
  9. OMIM :accession 125851
  10. OMIM :accession 609812
  11. OMIM :accession 610508
  12. OMIM :accession 612225
  13. OMIM :accession 613370
  14. OMIM :accession 313375
  15. OMIM :accession 606391
  16. May AL et al Prevalence of Cardiovascular Disease Risk Factors Among US Adolescents, 1999-2008 Pediatris, May 21, 2012 PMID: 22586506 http://pediatrics.aappublications.org/content/early/2012/05/15/peds.2011-1082.abstract
  17. Dabelea D, Stafford JM, Mayer-Davis EJ et al Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood. JAMA. 2017;317(8):825-835. Feb 28, 2017 PMID: 28245334 http://jamanetwork.com/journals/jama/article-abstract/2606400
  18. TODAY Study Group. Bjornstad P et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med 2021 Jul 29; 385:416. July 29 PMID: 34320286 https://www.nejm.org/doi/10.1056/NEJMoa2100165