A Systematic Review of the use of Precision Diagnostics in Monogenic Diabetes

Abstract

Monogenic forms of diabetes present opportunities for precision medicine as identification of the underlying genetic cause has implications for treatment and prognosis. However, genetic testing remains inconsistent across countries and health providers, often resulting in both missed diagnosis and misclassification of diabetes type. One of the barriers to deploying genetic testing is uncertainty over whom to test as the clinical features for monogenic diabetes overlap with those for both type 1 and type 2 diabetes. In this review, we perform a systematic evaluation of the evidence for the clinical and biochemical criteria used to guide selection of individuals with diabetes for genetic testing and review the evidence for the optimal methods for variant detection in genes involved in monogenic diabetes. In parallel we revisit the current clinical guidelines for genetic testing for monogenic diabetes and provide expert opinion on the interpretation and reporting of genetic tests. We provide a series of recommendations for the field informed by our systematic review, synthesizing evidence, and expert opinion. Finally, we identify major challenges for the field and highlight areas for future research and investment to support wider implementation of precision diagnostics for monogenic diabetes.

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

“…One French study systematically evaluated the use of SU or repaglinide after the genetic diagnosis at a median [IQR] duration of 0.75 [0-5.25] years, and reported that 29 of 51 (57%) patients displayed an HbA1c decrease. However, the duration of SU or repaglinide treatment in those who did respond was 5 [3][4][5][6][7][8][9] years, and at a mean of 12 years follow-up, 79% of the cohort were on insulin 45 . They also tried replacing insulin with SU for 10 patients, which was successful in three (no details given).…”

“…The PMDI was established in 2018 by the American Diabetes Association (ADA) in partnership with the European Association for the Study of Diabetes (EASD) to address the burgeoning need for better diabetes prevention and care through precision medicine 8 . The evidence for whom to test for monogenic diabetes, how to test them and how to interpret a gene variant, as well as for underpinning the link between the genetic test result and prognostics are covered as separate systematic reviews in this series, by other members of the PMDI addressing precision diagnostics and prognostics for monogenic diabetes 9,10 .…”