The prevention program for DKA in diabetic children aged 6-14 years, carried out in the Parma area during the last 8 years, was successful. Thanks to this program, cumulative frequency of DKA in new-onset IDDM decreased from 78% during 1987-1991 to 12.5% during 1991-1997. None of the newly diagnosed diabetic children aged 6-14 years and from the Parma area were ever admitted to the hospital for DKA after 1992.

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...

It is well known that hyperglycemia is associated with increased mortality from cardiovascular disease (CVD) and all-cause mortality. It has recently been reported that subjects with low fasting plasma glucose (FPG) levels also had a high risk of CVD and all-cause mortality (1). However, there is a paucity of information about the etiologic basis underlying the association between low FPG and increased CVD and all-cause mortality. Thus, in the present study, we investigated the association of FPG levels with white blood cell (WBC) counts, which indicate a state of low-grade systemic inflammation.We investigated the cross-sectional association of WBC counts with FPG levels among 3,256 Japanese men aged 34 -69 years. The subjects were divided into six categories according to FPG level: Ͻ80 mg/dl, 80 to Ͻ90 mg/dl, 90 to Ͻ100 mg/dl, 100 to Ͻ110 mg/dl, 110 to Ͻ126 mg/dl, and diabetes.The crude mean WBC counts were 6, 409, 6,308, 6,111, 6,111, 6,109, and 6,610 cells/mm 3 in the subjects with FPG levels of Ͻ80 mg/dl, 80 to Ͻ90 mg/dl, 90 to Ͻ100 mg/dl, 100 to Ͻ110 mg/dl, 110 to Ͻ126 mg/dl, and diabetes, respectively. The crude mean WBC counts differed significantly by FPG category and showed a U-shaped association with FPG levels (P value for quadratic trend Ͻ0.001). Even after adjusting for age, BMI, smoking, alcohol, health status, and other factors associated with elevated WBC count or glycometabolism, the respective adjusted-mean WBC counts were 6,273, 6,255, 6,175, 6,165, 6,075, and 6,429 cells/mm 3 . The WBC count maintained a U-shaped association with FPG level (P value for quadratic trend ϭ 0.041).Although it is well known that hyperglycemia is the cause of microvascular complications in several organs, there are few studies on the adverse effect of hypoglycemia. Early studies of hypoglycemia focused on brain damage and heart dysfunction. An acute decrease in FPG is recognized as the cause of them, whereas the long-term effect of low FPG remains unclear.Infection and inflammation may contribute to vascular injury and atherogenesis. Inflammation may also promote atherosclerotic plaque ruptures and thrombosis (2,3). WBC serves as an important biomarker for these disease processes.This study shows that the U-shaped association between WBC counts and FPG levels (especially low FPG levels) involves higher WBC counts that could not be linked to inflammatory disease or other factors or to any disease known to increase WBC counts. These findings suggest that a state of low-grade systemic inflammation may be present not only in diabetic subjects but also in people with low FPG, possibly explaining in part the high risk of CVD and all-cause mortality of such people. • (1) to clinical practice continues to be a major challenge (2,3). Physicians in training present a unique opportunity for shaping practice behavior. We tested the effect of an intramural contest on the outcome of diabetes management by 155 medical residents at a major U.S. teaching hospital. The contest was approved by the house staff leadership and w...

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Background: Autoimmune disorders are considered to be associated with a Th1 immune response while allergic diseases with a Th2 response. We carried out a study to determine whether there is an inverse relationship between allergic diseases in IgE-sensitized children or positive skin-prick test reactions to allergens and type 1 diabetes mellitus (DM1) in children. Methods: Sixty-three children with DM1 and 108 controls were enrolled. Parents of all children compiled a questionnaire on allergic diseases. All children underwent skin-prick tests for common aero-allergens and food-allergens. Results: A history of allergic symptoms, especially wheezing, asthma and allergic rhinitis was significantly less common in the group with DM1. Allergic symptoms in children with IgE sensitization or parental atopy were no more likely in children with DM1 than in normal control subjects. There was no association between skin-prick test results to inhalants and food allergens and DM1. Conclusions: Consistently with the Th1/Th2 paradigm, we observed a reduction in the frequency of allergic symptoms in children with DM1. However, our study did not succeed in demonstrating an inverse relation between Th1- and Th2-mediated diseases in children with IgE sensitization or an atopic genetic predisposition.