Diabetes and endocrinology
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Research outputs from the Diabetes/Endocrine service department at the RD&E.
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Item HbA(1c) screening for the diagnosis of diabetes. Reply to Brož J, Brabec M, Krollová P et al [letter](Springer, 2023-08-01) Young, K. G.; McGovern, A. P.; Barroso, I.; Hattersley, A. T.; Jones, A. G.; Shields, B. M.; Thomas, N. J.; Dennis, J. M.Item The evolving continuum of dysglycaemia: Non-diabetic hyperglycaemia in older adults(Wiley, 2023-07-01) Golding, J.; Hope, S. V.; Chakera, A. J.; Puttanna, A.Identifying non-diabetic hyperglycaemia (NDH) and intervening to halt the progression to type 2 diabetes has become an essential component of cardiovascular and cerebrovascular risk reduction. Diabetes prevention programs have been instigated to address the increasing prevalence of NDH and type 2 diabetes by targeting lifestyle modifications. Evidence suggests that the risk of progression from NDH to type 2 diabetes declines with age, and that a diagnosis of type 2 diabetes in older adults is not associated with the same risk of adverse consequences as it is in younger age groups. The current definition of NDH is not adjusted based on a person's age. Therefore, there is debate about the emphasis that should be placed upon a diagnosis of NDH in older adults. This article will explore the evidence and current clinical practice surrounding dysglycaemia through the spectrum of different age ranges, and the potential implications this has for older adults.Item Type 1 Diabetes Genetic Risk Score Differentiates Subgroups of Ketosis-Prone Diabetes(American Diabetes Association, 2023-07-01) Osafehinti, D.; Mulukutla, S. N.; Hampe, C. S.; Gaba, R.; Ram, N.; Weedon, M. N.; Oram, R. A.; Balasubramanyam, A.OBJECTIVE: To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and β+ and β- define the presence or absence of β-cell function. RESEARCH DESIGN AND METHODS: We compared T1D genetic risk scores (GRSs) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia. RESULTS: Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+β- > A+β+ = A-β- > A-β+. GRS of A+β- KPD was lower than that of a T1D cohort, and GRS of A-β+ KPD was higher than that of a type 2 diabetes cohort. GRS was lowest among African American patients, with a similar distribution across KPD subgroups. CONCLUSIONS: T1D genetic risk delineates etiologic differences among KPD subgroups. Patients with A+β- KPD have the highest and those with A-β+ KPD the lowest GRS.Item Bringing precision medicine to the management of pregnancy in women with glucokinase-MODY: a study of diagnostic accuracy and feasibility of non-invasive prenatal testing(Springer, 2023-08-01) Hughes, A. E.; Houghton, J. A. L.; Bunce, B.; Chakera, A. J.; Spyer, G.; Shepherd, M. H.; Flanagan, S. E.; Hattersley, A. T.AIMS/HYPOTHESIS: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management. METHODS: We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021. RESULTS: In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks. CONCLUSIONS/INTERPRETATION: Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.Item Correction to: The impact of population-level HbA(1c) screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis(Springer, 2023-08-01) Young, K. G.; McGovern, A. P.; Barroso, I.; Hattersley, A. T.; Jones, A. G.; Shields, B. M.; Thomas, N. J.; Dennis, J. M.