J Korean Diabetes.  2017 Sep;18(3):169-176. 10.4093/jkd.2017.18.3.169.

Genetic Diseases Associated with Diabetes Mellitus

• Noh J

• KMID: 2390870
• DOI: http://doi.org/10.4093/jkd.2017.18.3.169

Abstract

Whereas most people with diabetes mellitus have type 1 or type 2 diabetes, there are other inherited forms of diabetes, including single-gene forms of diabetes and rare genetic syndromes. Monogenic forms of pancreatic beta cell dysfunction include maturity-onset diabetes of the young (MODY) and neonatal diabetes, with MODY being the most common form of inherited diabetes. Mitochondrial diabetes and monogenic severe insulin resistance are also inherited forms of diabetes. In addition, more than 100 genetic diseases are known to be associated with diabetes mellitus. Diagnosis of inherited diabetes has important implications for patients, allowing personalized management and screening of their relatives. This review briefly presents genetic diseases associated with diabetes mellitus.

Keyword

Diabetes mellitus; Genetic diseases; inborn; Single-gene diabetes disorder

MeSH Terms

Diabetes Mellitus*
Diabetes Mellitus, Type 2
Diagnosis
Humans
Insulin Resistance
Insulin-Secreting Cells
Mass Screening

Reference

References

1. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med. 2001; 345:971–80.

2. Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue K. International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2006–2007. The diagnosis and management of monogenic diabetes in children. Pediatr Diabetes. 2006; 7:352–60.

3. Naylor RN, Greeley SA, Bell GI, Philipson LH. Genetics and pathophysiology of neonatal diabetes mellitus. J Diabetes Investig. 2011; 2:158–69.

4. Colombo C, Delvecchio M, Zecchino C, Faienza MF, Cavallo L, Barbetti F. Early Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation. Diabetologia. 2005; 48:2439–41.

5. Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006; 355:456–66.

6. Støy J, Edghill EL, Flanagan SE, Ye H, Paz VP, Pluzhnikov A, Below JE, Hayes MG, Cox NJ, Lipkind GM, Lipton RB, Greeley SA, Patch AM, Ellard S, Steiner DF, Hattersley AT, Philipson LH, Bell GI. Neonatal Diabetes International Collaborative Group. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007; 104:15040–4.

7. Njølstad PR, Søvik O, Cuesta-Muñoz A, Bjørkhaug L, Massa O, Barbetti F, Undlien DE, Shiota C, Magnuson MA, Molven A, Matschinsky FM, Bell GI. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med. 2001; 344:1588–92.

8. Murphy R, Turnbull DM, Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med. 2008; 25:383–99.

9. Agarwal AK, Garg A. Genetic disorders of adipose tissue development, differentiation, and death. Annu Rev Genomics Hum Genet. 2006; 7:175–99.

10. Tritos NA, Mantzoros CS. Clinical review 97: syndromes of severe insulin resistance. J Clin Endocrinol Metab. 1998; 83:3025–30.

11. Iannello S, Bosco P, Cavaleri A, Camuto M, Milazzo P, Belfiore F. A review of the literature of Bardet-Biedl disease and report of three cases associated with metabolic syndrome and diagnosed after the age of fifty. Obes Rev. 2002; 3:123–35.

12. Antosik K, Borowiec M. Genetic factors of diabetes. Arch Immunol Ther Exp (Warsz). 2016; 64(Suppl 1):157–60.

13. Milunsky A, Neurath PW. Diabetes mellitus in Down's syndrome. Arch Environ Health. 1968; 17:372–6.

14. Bergholdt R, Eising S, Nerup J, Pociot F. Increased prevalence of Down's syndrome in individuals with type 1 diabetes in Denmark: a nationwide population-based study. Diabetologia. 2006; 49:1179–82.

15. Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, Bailey R, Nejentsev S, Field SF, Payne F, Lowe CE, Szeszko JS, Hafler JP, Zeitels L, Yang JH, Vella A, Nutland S, Stevens HE, Schuilenburg H, Coleman G, Maisuria M, Meadows W, Smink LJ, Healy B, Burren OS, Lam AA, Ovington NR, Allen J, Adlem E, Leung HT, Wallace C, Howson JM, Guja C, Ionescu-Tîrgovişte C. Genetics of Type 1 Diabetes in Finland. Simmonds MJ, Heward JM, Gough SC. Wellcome Trust Case Control Consortium, Dunger DB, Wicker LS, Clayton DG. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007; 39:857–64.

16. Lima FA, Moreira-Filho CA, Ramos PL, Brentani H, Lima Lde A, Arrais M, Bento-de-Souza LC, Bento-de-Souza L, Duarte MI, Coutinho A, Carneiro-Sampaio M. Decreased AIRE expression and global thymic hypofunction in Down syndrome. J Immunol. 2011; 187:3422–30.

17. Bojesen A, Høst C, Gravholt CH. Klinefelter's syndrome, type 2 diabetes and the metabolic syndrome: the impact of body composition. Mol Hum Reprod. 2010; 16:396–401.

18. Ibarra-Gasparini D, Altieri P, Scarano E, Perri A, Morselli-Labate AM, Pagotto U, Mazzanti L, Pasquali R, Gambineri A. New insights on diabetes in Turner syndrome: results from an observational study in adulthood. Endocrine 2017. doi: 10.1007/s12020-017–1336-z. [Epub ahead of print].

19. Cnop M, Mulder H, Igoillo-Esteve M. Diabetes in Friedreich ataxia. J Neurochem. 2013; 126(Suppl 1):94–102.

20. Podolsky S, Leopold NA, Sax DS. Increased frequency of diabetes mellitus in patients with Huntington's chorea. Lancet. 1972; 1:1356–8.

21. Farrer LA. Diabetes mellitus in Huntington disease. Clin Genet. 1985; 27:62–7.

22. Ørngreen MC, Arlien-Søborg P, Duno M, Hertz JM, Vissing J. Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol. 2012; 259:912–20.

23. Lanng S, Thorsteinsson B, Nerup J, Koch C. Influence of the development of diabetes mellitus on clinical status in patients with cystic fibrosis. Eur J Pediatr. 1992; 151:684–7.

24. Moran A, Brunzell C, Cohen RC, Katz M, Marshall BC, Onady G, Robinson KA, Sabadosa KA, Stecenko A, Slovis B. CFRD Guidelines Committee. Clinical care guidelines for cystic fibrosis-related diabetes: a position statement of the American Diabetes Association and a clinical practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine Society. Diabetes Care. 2010; 33:2697–708.

25. Pelusi C, Gasparini DI, Bianchi N, Pasquali R. Endocrine dysfunction in hereditary hemochromatosis. J Endocrinol Invest. 2016; 39:837–47.