SummaryBackgroundKCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients.MethodsIn this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA1c and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817.Findings90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5·5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10·2 years (IQR 9·3–10·8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA1c and sulfonylurea at all time points (ie, pre-transfer [for HbA1c], year 1, and most recent follow-up; n=64)—median HbA1c was 8·1% (IQR 7·2–9·2; 65·0 mmol/mol [55·2–77·1]) before transfer to sulfonylureas, 5·9% (5·4–6·5; 41·0 mmol/mol [35·5–47·5]; p<0·0001 vs pre-transfer) at 1 year, and 6·4% (5·9–7·3; 46·4 mmol/mol [41·0–56·3]; p<0·0001 vs year 1) at most recent follow-up (median 10·3 years [IQR 9·2–10·9]). In the same patients, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14–0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12–0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20·5 years [IQR 10·5–24·0] vs 4·1 years [1·3–10·2]; p=0·0005). Initial improvement was noted following transfer to sulfo...

AimsTo test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients.MethodsAll consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin.ResultsMean baseline age was 62±9 years, and follow-up 4.7±1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89–0.99, p = 0.033)). Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89–0.99, p = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86–0.98, p = 0.014)). Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins.ConclusionsThe cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional “fixed” cohort or propensity score analyses.

Background: Continuous glucose monitoring (CGM), which enables real-time glucose display and trend information as well as real-time alarms, can improve glycemic control and quality of life in patients with diabetes mellitus. Previous reports have described strategies to extend the useable lifetime of a single sensor from 1-2 weeks to 28 days. The present multisite study describes the characterization of a sensing platform achieving 90 days of continuous use for a single, fully implanted sensor. Method: The Senseonics CGM system is composed of a long-term implantable glucose sensor and a wearable smart transmitter. Study subjects underwent subcutaneous implantation of sensors in the upper arm. Eight-hour clinic sessions were performed every 14 days, during which sensor glucose values were compared against venous blood lab reference measurements collected every 15 minutes using mean absolute relative differences (MARDs). Results: All subjects (mean ± standard deviation age: 43.5 ± 11.0 years; with 10 sensors inserted in men and 14 in women) had type 1 diabetes mellitus. Most (22 of 24) sensors reported glucose values for the entire 90 days. The MARD value was 11.4 ± 2.7% (range, 8.1-19.5%) for reference glucose values between 40-400 mg/dl. There was no significant difference in MARD throughout the 90-day study ( P = .31). No serious adverse events were noted. Conclusions: The Senseonics CGM, composed of an implantable sensor, external smart transmitter, and smartphone app, is the first system that uses a single sensor for continuous display of accurate glucose values for 3 months.

Introduction: The current study aimed to assess recent acute myocardial infarction (AMI) mortality rates and trends in Romania between 1994 and 2017. This dataset is a necessity in the context of the current improvement of emergency protocols, medical addressability, and modernization of hospital infrastructure. Materials and Methods: The study is a retrospective analysis of an anonymized mortality database containing all deaths registered in Romania during 1994–2017. AMI crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated using the European Standard Population. Poisson regression was used for calculating the annual percentage change (APC) in mortality, subsequently used to make mortality predictions through the year 2030. Results: There were 197,152 AMI deaths in women (39.3% of total AMI), and 304,644 (60.7%) in men. Mortality rates were higher in men as compared with women for the entire time covered by the study. Based on the 1994–2017 ASMR dynamics, predictions for the year 2030 showed an overall AMI ASMR of 70.9 (95% CI 69.9–71.9), with gender analysis showing 46.8 (95% CI 45.8–47.9) in women and 104.1 (95% CI 102.3–105.8) in men. Conclusion: Acute myocardial infarction age-standardized mortality rates decreased significantly in Romania between 1994 and 2017 in close correlation to the implementation of national healthcare programs.

We found no changes in age at onset, which combined with an increase in survival with diabetes lead to a significant increase in age at death over the six decades analyzed.

In this report, we present the first known case of intermediate developmental delay, epilepsy and permanent neonatal diabetes (DEND) syndrome caused by a Q52R mutation in the KCNJ11 gene who was successfully switched (at age 1.3 years) to sulphonylurea monotherapy, namely glibenclamide. The most recent evaluation, after 2 years, showed a glycated hemoglobin level of 6.0% (42 mmol/mol). This mutation is so severe that none of the previously reported four cases were able to switch from insulin to sulphonylurea monotherapy. The Q52R mutation seems to have a chance of positive response to glibenclamide administered every 3–6 h instead of the classical 8–12 h, in doses around or above 2.5 mg/kg/day.

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This home-use study of a fully implantable, long-term continuous glucose sensor shows excellent performance in nocturnal hypoglycemia detection in T1DM patients. The apparent lack of NSA affecting the implanted sensor and the high specificity of the hypoglycemic alarm expedite the recovery from nighttime hypoglycemia.