Improvements in Awareness and Testing Have Led to a Threefold Increase Over 10 Years in the Identification of Monogenic Diabetes in the U.K

TY - JOUR

T1 - Improvements in Awareness and Testing Have Led to a Threefold Increase Over 10 Years in the Identification of Monogenic Diabetes in the U.K

AU - Pang, Lewis

AU - Colclough, Kevin C.

AU - Shepherd, Maggie H.

AU - McLean, Joanne

AU - Pearson, Ewan R.

AU - Ellard, Sian

AU - Hattersley, Andrew T.

AU - Shields, Beverley M.

N1 - Funding. M.H.S. is a National Institute for Health Research (NIHR) senior nurse and midwife research leader. M.H.S., A.TH., and B.M.S. are core members of the NIHR Exeter Clinical Research Facility, which is a partnership between the University of Exeter Medical School College of Medicine and Health and Royal Devon and Exeter NHS Foundation Trust. The GDNs were supported with funding from Health Education England and from the Scottish Government. © 2022 by the American Diabetes Association. Funding Information: Acknowledgments. This paper has been funded by research grants from CONACyT, Grant 81965, and from PAPIIT–UNAM, Grant 104408. Funding Information: This paper has been funded by research grants from CONACyT, Grant 81965, and from PAPIIT–UNAM, Grant 104408. Publisher Copyright: © 2022 by the American Diabetes Association.

PY - 2022/3/1

Y1 - 2022/3/1

N2 - OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes. In 2009, >80% of U.K. cases were estimated to be misdiagnosed. Since then, there have been a number of initiatives to improve the awareness and detection of MODY, including education initiatives (Genetic Diabetes Nurse [GDN] project), the MODY probability calculator, and targeted next-generation sequencing (tNGS). We examined how the estimated prevalence of MODY and other forms of monogenic diabetes diagnosed outside the neonatal period has changed over time and how the initiatives have impacted case finding. RESEARCH DESIGN AND METHODS: U.K. referrals for genetic testing for monogenic diabetes diagnosed >1 year of age from 1 January 1996 to 31 December 2019 were examined. Positive test rates were compared for referrals reporting GDN involvement/MODY calculator use with those that did not. RESULTS: A diagnosis of monogenic diabetes was confirmed in 3,860 individuals, more than threefold higher than 2009 (1 January 1996 to 28 February 2009, n = 1,177). Median age at diagnosis in probands was 21 years. GDN involvement was reported in 21% of referrals; these referrals had a higher positive test rate than those without GDN involvement (32% vs. 23%, P < 0.001). MODY calculator usage was indicated in 74% of eligible referrals since 2014; these referrals had a higher positive test rate than those not using the calculator (33% vs. 25%, P = 0.001). Four hundred ten (10.6%) cases were identified through tNGS. Monogenic diabetes prevalence was estimated to be 248 cases/million (double that estimated in 2009 because of increased case finding). CONCLUSIONS: Since 2009, referral rates and case diagnosis have increased threefold. This is likely to be the consequence of tNGS, GDN education, and use of the MODY calculator.

AB - OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes. In 2009, >80% of U.K. cases were estimated to be misdiagnosed. Since then, there have been a number of initiatives to improve the awareness and detection of MODY, including education initiatives (Genetic Diabetes Nurse [GDN] project), the MODY probability calculator, and targeted next-generation sequencing (tNGS). We examined how the estimated prevalence of MODY and other forms of monogenic diabetes diagnosed outside the neonatal period has changed over time and how the initiatives have impacted case finding. RESEARCH DESIGN AND METHODS: U.K. referrals for genetic testing for monogenic diabetes diagnosed >1 year of age from 1 January 1996 to 31 December 2019 were examined. Positive test rates were compared for referrals reporting GDN involvement/MODY calculator use with those that did not. RESULTS: A diagnosis of monogenic diabetes was confirmed in 3,860 individuals, more than threefold higher than 2009 (1 January 1996 to 28 February 2009, n = 1,177). Median age at diagnosis in probands was 21 years. GDN involvement was reported in 21% of referrals; these referrals had a higher positive test rate than those without GDN involvement (32% vs. 23%, P < 0.001). MODY calculator usage was indicated in 74% of eligible referrals since 2014; these referrals had a higher positive test rate than those not using the calculator (33% vs. 25%, P = 0.001). Four hundred ten (10.6%) cases were identified through tNGS. Monogenic diabetes prevalence was estimated to be 248 cases/million (double that estimated in 2009 because of increased case finding). CONCLUSIONS: Since 2009, referral rates and case diagnosis have increased threefold. This is likely to be the consequence of tNGS, GDN education, and use of the MODY calculator.

UR - https://www.scopus.com/pages/publications/85125882996

U2 - 10.2337/dc21-2056

DO - 10.2337/dc21-2056

M3 - Article

C2 - 35061023

SN - 0149-5992

VL - 45

SP - 642

EP - 649

JO - Diabetes Care

JF - Diabetes Care

IS - 3

ER -