Genomics in general practice

Disease specific topics

Diabetes

Genomics in general practice
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  1. Summary of genetic tests

Diabetes

PRACTICE POINT

Types 1 and 2 diabetes are multifactorial.

 Approximately 2% of people with diabetes have maturity onset diabetes of the young (MODY), which is caused by a dominantly inherited variant in one of several known genes. It is important to identify these patients and family members, as there are implications for clinical management, including choice of treatment, prognosis and reproduction.

Polygenic risk scores for type 1 and type 2 diabetes exist but their clinical utility remains uncertain. 

What do I need to know?

MODY typically presents in the second to fourth decade of life, and does not fit the typical clinical picture of either types 1 or 2 diabetes. Presentation is often subacute or incidental. Many are misdiagnosed as types 1 or 2 diabetes.

MODY is the only type of diabetes caused by a single gene mutation. Mutations in 13 genes are known to cause MODY. The most prevalent mutations are in the HNF1A, GCK and HNF4A genes. GCK-MODY constitutes 10–60% of all MODY cases.

Testing for MODY should be considered in individuals with early onset diabetes with atypical features (ie not clearly type 1 or type 2):

  • atypical type 1 diabetes
  • no history of diabetic ketoacidosis
  • prandial plasma C-peptide >200 pmol/L and >5 years post-diagnosis of type 1 diabetes
  • atypical type 2 diabetes
  • <35 years of age
  • absence of features of insulin resistance
  • no obesity
  • no dyslipidaemia
  • no hypertension
  • no polycystic ovary syndrome
  • strong family history of diabetes

If MODY is suspected, assess risk using the calculator available at the UK site.

When should I refer?

Individuals with suspected MODY should be referred to an endocrinologist for assessment and consideration of genetic testing.

Further reading

  • Carroll RW, Murphy Monogenic diabetes: A diagnostic algorithm for clinicians. Genes (Basel) 2013;4(4):522–35.
  • Bishay RH, Greenfield A review of maturity onset diabetes of the young (MODY) and challenges in the management of glucokinase-MODY. Med J Aust 2016;205(10):480–85.
  • Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine. Curr Diabetes Rev. 2020;16(8):807-819
  • Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes. Int J Mol Sci 2020 Mar 2;21(5):1703.

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