Search

Objectives: This study aimed to evaluate the frequency of diabetic ketoacidosis (DKA) and its associated factors at the diagnosis of type 1 diabetes (T1D) in French children and adolescents prior to launching a public-health campaign of information to prevent DKA., Patients and Methods: Over a 1-year period, 1299 youngsters (aged < 15 years) were diagnosed with T1D at 146 paediatric centres in all regions of France. Age, gender, duration of symptoms, patient's pathway to diagnosis, clinical and biological signs, and family history of T1D were collected for each newly diagnosed patient. DKA was defined as pH < 7.30 or bicarbonate < 15 mmol/L, and severe DKA as pH < 7.10 or bicarbonate < 5 mmol/L., Results: At the time of diagnosis, 26% of the children were aged 0-5 years, 34% were 5-10 years and 40% were 10-15 years. The overall prevalence of DKA was 43.9% (0-5 years: 54.2%; 5-10 years: 43.4%; and 10-15 years: 37.1%) and 14.8% for severe DKA (0-5 years: 16.6%; 5-10 years: 14.4%; and 10-15 years: 13.9%; < 2 years: 25.3%). Severe DKA was more frequent when the child was hospitalized at the family's behest (26.6%) than when referred by a general practitioner (7.6%) or paediatrician (5.1%; 30.6%, 53.7% and 9.2%, respectively, by patients' age group). The frequency of DKA decreased to 20.1% (severe DKA: 4.4%) in families with a history of T1D. Multivariate analysis showed that age, pathway to diagnosis, duration of polyuria/polydipsia (< 1 week) and family history of T1D were associated with the presence of DKA, while pathway to diagnosis and family history of T1D were associated with severe DKA., Conclusion: DKA at the time of T1D diagnosis in children and adolescents is frequent and often severe. Patients' age, pathway to hospitalization and family history of diabetes were the main factors associated with DKA. These data suggest that a public-health campaign to prevent DKA at diagnosis can help reduce the frequency of DKA and also provide baseline data for evaluating the efficacy of such a campaign., (Copyright © 2014. Published by Elsevier Masson SAS.)

Aim: PREDICTIVE (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n=1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes., Methods: Patients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA(1c), fasting blood glucose and variability of fasting blood glucose) and weight change., Results: The incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P<0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA(1c), by -0.6% and -0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by -1.4mmol/L and -1.9mmol/L respectively; and FBG variability, by -0.8mmol/L and -0.3mmol/L, respectively (P<0.0001 for all)., Conclusion: Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.

Objectives: To describe the present status of type 1 diabetes care in France and study the relations between clinical and socio-economic variables on one hand and disease management and prevalence of complications on the other hand., Methods: A random sample of 365 French specialists in diabetes care performed a cross-sectional study and included consecutively 562 children aged 10-16 and 1691 adults aged 16-45, with more than 2 years of type 1 diabetes. The main outcome measures were the prevalence of complications (retinal, renal, lower-limb, cardiovascular, ketoacidosis); disease management parameters (blood pressure, HbA1c, daily number of insulin injections, frequency of visits to a specialist in diabetes, membership of a patient association); socio-economic status as a score, and treatments received., Results: Retinal complications were rare in children (0.7%) and common in adults (28.3%). 10.2% children and 15.2% adults had micro- or macro-albuminuria, 4.7% adults had plasma creatinine >or=150 micromol/L. Only 15% children and 26% adults had HbA1c<7%, 86.2% children and 62.7% adults had blood pressure<130/85 mmHg; 58% children and 80% adults had at least 3 daily insulin injections. In adults, the risk of experiencing at least one complication was linked significantly with diabetes duration, HbA1c, and socio-economic status. Age, sex, type of insulin therapy, tobacco consumption, and blood pressure control were not significant parameters. Ketoacidosis in the preceding year was only linked with HbA1C and socio-economic status., Conclusion: Although this sample of patients had overall a fair socio-economic status and were followed-up by specialists of diabetes care, metabolic and blood pressure control were not optimal. The care of French type 1 diabetics could probably be improved by a stricter control of glycaemia and blood pressure, and an earlier use of intensive insulin treatment, with a particular focus on adolescents and patients with the lowest socio-economic status.

In the last twenty years, blood glucose self-monitoring has attained a nearly optimal level, with reliability, easiness, quickness and safety, which makes it tolerable to a greater number of patients and allows young diabetics to make more easily something which is mandatory to the management of type 1 diabetes. The principles of treatment are identical in children, adolescents and adults. However, many patients experience difficulties in applying the ideal therapeutic model. This must be particularly taken into account in children, who are in a stage of full intellectual and psychological development. Inappropriate demands can drive them to failure and go against the main objective at this period of life, which is education. Reference documents help pediatricians to the daily practice of home blood glucose monitoring and, more generally, management of childhood diabetes: ISPAD Consensus Guidelines (ISPAD=International Society for Pediatric and Adolescent Diabetes), which has been translated in French, and Cahiers de l'AJD (AJD Note books), for educating new patients. Blood glucose monitoring is recommended: to evaluate the glycemic response to the effect of insulin; to confirm hypoglycemia; to prevent hyperglycemia in case of disease; in case of physical exercise. The frequency of home blood glucose monitoring should be individualized, depending on the acceptability for the young patients and the insulin therapeutic regimen.

Background: We have previously observed associations of the T-allele of the exon 18 variant (ACC --> ACT; Thr759Thr) of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus (T2DM). Here we assess beta-cell function and insulin sensitivity in carriers of different genotypes at this locus., Methods: Pre-hepatic insulin secretion rates (ISR) derived by deconvolution of circulating C-peptide levels, and glucose clearance were assessed during graded infusions of intravenous glucose in CC-homozygous (n=6) and CT-heterozygous (n=6) nondiabetic relatives of CT-heterozygous type 2 diabetic subjects., Results: Average ISR over the duration of the study, adjusted for sex, age, BMI and prevailing glucose levels, were lower in CT-heterozygous subjects as compared with CC-homozygous subjects (3.91 +/- 0.40 vs. 4.84 +/- 0.28 pmol/kg x min(-1); p=0.048). The correlation curves relating ISR to glucose levels were significantly different in the two groups (analyses of covariance p=0.029). Glucose clearance was similar in both groups., Conclusions: Insulin secretion rates, but not insulin sensitivity, assessed during graded infusion of glucose were mildly decreased in nondiabetic relatives of type 2 diabetic subjects, who carry the at risk T-allele of exon 18 variant of the SUR1 gene. These results suggest that the at-risk allele might have a small effect on pancreatic B-cell function and contribute to the development of T2DM in these families.

The relationship between altered insulin secretion and impaired glucose tolerance was studied in 32 non-obese subjects aged 14-49 years with islet-cell antibodies (ICA) and fasting blood glucose below 7.9 mmol/l, using oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Glucose tolerance was normal in 19 subjects, impaired (IGT) in 4 and satisfied diabetic criteria in 9. Fifteen of these subjects and 8 ICA-negative controls also underwent a hyperglycaemic clamp (10 mmol/l) and a glucose-potentiated IV arginine bolus. Acute insulin response to IVGTT and insulin and C-peptide responses to the hyperglycaemic clamp and the arginine bolus were dramatically lower (p < 0.001) in diabetic and IGT subjects than in ICA-positive patients with normal glucose tolerance and control subjects. Insulin responses to the three tests were inversely correlated with plasma glucose levels and the area under the curve of OGTT. The correlations between the degree of glucose tolerance and insulin responses to IVGTT, the hyperglycaemic clamp and the arginine bolus were virtually identical. It is concluded that insulin responses to the three stimuli were severely altered in ICA-positive patients with impaired glucose tolerance or asymptomatic diabetes, normal in normotolerant ICA-positive subjects, and correlated with glucose tolerance.

Insulin dependent diabetic adolescent girls show a tendency towards excess weight. The relationship between insulin resistance and body mass index (BMI) was investigated in 23 Type 1 adolescents aged 13-20 yr. These patients body mass indexes spanned from 19.8 to 30.5. Excess weight was evaluated using Z-scores, corrected for age with reference to french standards. 9 patients with a Z-score greater than 2 were considered as obese. Insulin sensibility was measured using the hyperinsulinaemic euglycaemic clamp (insulin infusion rate, 1 mU kg-1 min-1). The mean glucose infusion rate during the clamp was low in the diabetic girls (2.29 +/- 1.35 mg kg-1 min-1), confirming the existence of insulin resistance. However, the degree of insulin resistance was not correlated with the excess in weight (glucose infusion rate, 2.23 +/- 1.24 vs 2.33 +/- 1.46 mg kg-1 min-1 in the obese and the non-obese patients, respectively). None of the factors which influence on insulin sensitivity could explain this lack of correlation, the obese patients showing greater daily insulin doses (1.36 +/- 0.22 vs 1.22 +/- 0.25 unit kg-1 day-1) and worse metabolic control (Hba1C, 10.9 +/- 1.4 vs 10.2 +/- 2.0%). Insulin resistance was significantly correlated with free fatty acid levels during the clamp.

Superoxide dismutase, glutathione peroxidase and glutathione reductase activities were measured in erythrocytes of 214 young patients with insulin-dependent diabetes and 37 healthy subjects with similar age and sex distribution. The diabetic patients were divided into groups and subgroups according to sex, age, duration of disease, existence of diabetes complications and family history of atherogenic risks. Data analysis was performed by comparing enzyme activities in subgroups according to the degree of diabetes control and the plasmatic level of various lipid fractions. Results showed that superoxide dismutase, glutathione peroxidase and glutathione reductase activities in young diabetic patients were similar to those in controls, except for patients with retinopathy, whose glutathione peroxidase activity was decreased. This last finding might suggest that there is a relationship between the development of diabetic microvascular complications and the accumulation of free radicals and peroxide lipids.

Insulin resistance was explored in vivo and in vitro in 3 lipoatrophic diabetic girls (12, 15 and 19 years old = L1, L2 and L3). Patients L1 and L2 were explored with fasting hyperglycaemia (9 mmol/l); patient L3 was normoglycaemic. All had abnormal OGTT with marked hyperinsulinemia. Their basal glucose productions, measured by [6,6(-2)H] glucose constant infusion, were 3.3, 2.6 and 3.4 mg kg-1 min-1, respectively; they did not correlate with fasting plasma glucose. Glucose production in response to a 2 mg kg-1 min- unlabeled glucose infusion, was normally suppressed in L2, but was incompletely suppressed (by 1.5 mg kg-1 min-1) in L1 and L3. The dose-response curve during hyperinsulinemic euglycaemic clamp at 1, 2 and 10 mU kg-1 min-1 insulin infusion was shifted to the right in all three patients. However the maximal glucose disposal rates were close to normal (9 and 9 mg kg-1 min-1) in L1 and L3, while it remained very low (3.6 mg kg-1 min-1 at 10 mU kg-1 min-1 insulin infusion) in L2. The endogenous insulin secretion (plasma C-peptide) was also incompletely suppressed during insulin infusion. Thus, the in vivo insulin resistance of lipoatrophic diabetes concerns not only glucose disposal but also hepatic glucose output and insulin secretion; in addition, the alterations of glucose metabolism were not the same in all subjects. The in vitro studies showed no pre-receptor defect (anti-insulin antibodies, insulin receptor antibodies). Insulin binding to erythrocytes and cultured fibroblasts was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

The information and counselling of diabetic patients and their families requires for the practitioner to know about some fundamental aspects of diabetes and in particular, to distinguish between the different types of diabetes with different causes, pathogenetic mechanism and modes of inheritance. Recent developments in the fields of immunogenetics have improved the understanding of type I diabetes, an auto-immune disease associated with HLA and made possible the identification of genetically susceptible individuals. The etiology of type II diabetes, by far the most frequent form, remains unknown. In the absence of genetical markers, the screening of predisposed subjects is, however, useful in order to propose preventive measures.