Diagnosis of monogenic diabetes: 10-Year experience in a large multi-ethnic diabetes center.

AIMS/INTRODUCTION: Monogenic diabetes accounts for approximately 1-2% of all diabetes, and is difficult to distinguish from type 1 and type 2 diabetes. Molecular diagnosis is important, as the molecular subtype directs appropriate treatment. Patients are selected for testing according to clinical criteria, but up to 80% of monogenic diabetes in the UK has not been correctly diagnosed. We investigated outcomes of genetic testing in our center to compare methods of selecting patients, and consider avenues to increase diagnostic efficiency. MATERIALS AND METHODS: We reviewed 36 probands tested for monogenic diabetes in the last 10 years in a large adult diabetes outpatient clinic, serving an ethnically diverse urban population. We compared published clinical criteria and an online maturity onset diabetes of the young calculator applied to these 36 patients, and presented the predictions together with the molecular results. RESULTS: The overall mutation detection rate was 42%, reflecting the strict clinical selection process applied before genetic testing. Both methods had high sensitivity for identifying patients with mutations: 88 and 89% for the clinical criteria and online calculator, respectively. Cascade testing in a total of 16 relatives led to diagnosis of a further 13 cases. CONCLUSIONS: Existing patient selection criteria were effective in identifying patients with monogenic forms of diabetes, but the number of patients missed using these strict criteria is unknown. Because of the potential savings resulting from correct molecular diagnosis, it is possible that testing a larger pool of patients using less stringent selection criteria would be cost-effective. Further evidence is required to inform this assessment.

Determinants of glycaemic control in type 1 diabetes during intensified therapy with multiple daily insulin injections or continuous subcutaneous insulin infusion: importance of blood glucose variability.

BACKGROUND AND METHODS: We investigated the factors that determine the best glycaemic control on multiple daily insulin (MDI) injections and continuous subcutaneous insulin infusion (CSII), and the hypothesis that blood glucose variability is a major determinant of control and that the resultant HbA(1c) on MDI correlates with the improvement achieved by CSII. We studied 30 type 1 diabetic subjects already receiving MDI. Renewed attempts to improve control on MDI were made for a median of five months, and then the subjects were switched to CSII. The variability of within-day and between-day blood glucose concentrations was calculated from blood glucose self-monitoring data. RESULTS: HbA(1c) during MDI varied from 5.7 to 11.7% (mean +/- SD, 8.5 +/- 1.4%). Within- and between-day blood glucose variability correlated with HbA(1c) on MDI (r = 0.59, p < 0.001; r = 0.48, p < 0.03). Within-day variability remained an independent predictor of HbA(1c) on MDI. Mean HbA(1c) improved with CSII (to 7.3 +/- 0.9%, p < 0.001), but reduction in HbA(1c) was variable and was related to the HbA(1c) on MDI (r = 0.79, p < 0.001) and within-day variability (r = 0.56, p < 0.01). Similar results were observed for subjects treated only with glargine-based MDI. CONCLUSIONS: The best glycaemic control achievable on MDI is related to blood glucose variability-those with the largest swings in blood glucose retaining the highest HbA(1c). The improvement in control achieved by CSII is related to HbA(1c) and blood glucose variability on MDI. Pump therapy is most effective in those worst controlled on MDI.