Acta Diabetologica

The absolute glucose disposal of insulin glargine (Lantus) was compared to that of regular human insulin in healthy subjects (n=20) using the euglycaemic clamp technique in a single-dose, double-blind, randomized, two-way crossover design. Subjects received 30-minute intravenous infusions of insulin glargine (0.1 IU/kg) or human insulin (0.1 IU/kg) and a 20% glucose solution infused at a variable rate to maintain euglycaemia at the subject’s baseline glucose level. At equal baseline blood glucose levels (4.42 mmol/l [range, 4.00–5.16 mmol/l] and 4.42 mmol/l [range, 4.01–4.94 mmol/l], respectively), the area under the glucose infusion rate (GIR) time curves from 0–6 hours (AUC(0–6h)) was within the bioequivalence range (insulin glargine, 663.92 mg/kg; human insulin, 734.85 mg/kg). Both the time to maximum GIR and the suppression of serum C-peptide were similar with insulin glargine and human insulin. The resulting maximum serum insulin concentrations (Cmax) were 151.16 µIU/ml and 202.23 µIU/ml, and the time to Cmax (Tmax) was 30 minutes (the duration of the infusion). The observed differences in the Cmax (the mean value for insulin glargine was about 25% lower than that of human insulin) could be explained by lower cross-reactivity of insulin glargine in the human insulin radioimmunoassay. The employed intravenous route, though definitely not the intended clinical use of insulin glargine, provided the clinical evidence in healthy subjects that on a molar basis insulin glargine is equipotent to regular human insulin regarding glucose disposal.

Có một nhu cầu chưa được đáp ứng giữa các nhà cung cấp dịch vụ chăm sóc sức khỏe trong việc xác định các nhóm con của bệnh nhân mắc bệnh tiểu đường type 2, những người có khả năng cao nhất phản ứng với điều trị. Dữ liệu được lấy từ hồ sơ y tế điện tử của những người tham gia một nghiên cứu quan sát, hồi cứu ở Italy. Chúng tôi đã sử dụng các mô hình hồi quy logistic để đánh giá tỷ lệ đạt được giảm hemoglobin glycated (HbA1c) ≥ 1.0% sau 12 tháng điều trị với liraglutide (kết quả chính), theo các yếu tố liên quan đến bệnh nhân khác nhau. Phân tích RECursive Partitioning and AMalgamation (RECPAM) được sử dụng để xác định các nhóm bệnh nhân đồng nhất rõ rệt với các tỷ lệ khác nhau đạt được kết quả chính. Dữ liệu từ 1325 bệnh nhân được bao gồm, trong đó có 577 (43.5%) đạt được giảm HbA1c ≥ 1.0% (10.9 mmol/mol) sau 12 tháng. Hồi quy logistic cho thấy rằng với mỗi 1% HbA1c gia tăng tại thời điểm đầu, tỷ lệ đạt được kết quả này tăng 3.5 lần (95% CI: 2.90–4.32). Qua phân tích RECPAM, năm nhóm bệnh nhân phản ứng khác nhau đã được xác định, với HbA1c tại thời điểm đầu và thời gian mắc bệnh tiểu đường là hai biến phân tách. Bệnh nhân trong nhóm kiểm soát kém nhất (Lớp 1 RECPAM, HbA1c trung bình tại thời điểm đầu > 9.1% [76 mmol/mol]) có khả năng đạt được kết quả gấp 28 lần so với bệnh nhân trong nhóm kiểm soát tốt nhất (HbA1c trung bình tại thời điểm đầu ≤ 7.5% [58 mmol/mol]). Giảm HbA1c trung bình so với thời điểm đầu lớn tới -2.2% (24 mol/mol) ở nhóm trước đó so với -0.1% (1.1 mmol/mol) ở nhóm sau. Giảm cân trung bình dao động từ 2.5 đến 4.3 kg giữa các nhóm RECPAM. Phản ứng đường huyết với liraglutide chủ yếu bị ảnh hưởng bởi mức HbA1c tại thời điểm đầu và, ở mức độ thấp hơn, bởi thời gian mắc bệnh tiểu đường.

Les AA. ont mesuré l'activité beta-glucuronidasique dans le sérum de 41 sujets avec une tolérance au glucose diminuée (diabète chimique) et dans un groupe de contrôle de 41 sujets sains. Les résultats ont été les suivants: 1) les sujets normaux de sexe masculin présentent des niveaux sériques de cet enzyme plus élevés que ceux qui ont été observés chez les femmes; 2) les femmes avec diabète chimique présentent des niveaux plus élevés que ceux qui ont été observés chez les femmes saines; 3) il existe une certaine tendance des niveaux enzymatiques du sérum à l'augmentation avec l'âge chez tous les deux groupes; 4) la charge de glucose ne modifie pas les niveaux enzymatiques du sérum; 5) il existe un petit groupe de sujets avec diabète chimique qui présentent des niveaux enzymatiques abnormement élevés; 6) les femmes normales, qui sont soumises à l'administration de contraceptives orales, présentent des niveaux plus élevés que ceux observés chez les autres femmes normales qui n'assument pas le médicament, sans présenter intolerance au glucose. Les AA. discutent sur ces résultats en comparaison des corrélations entre diabète et athérosclérose.

Childhood obesity increases the risk of morbidity whether or not obesity persists into adulthood. Measurement of body fat content using bioimpedance analysis (BIA) is a useful tool in epidemiologic studies. Both tricep skinfold thickness (TST, mm) and body mass index (BMI, kg/m2) are indirect, simple methods and easy to perform for assessing body composition. These methods are generally accepted as good clinical measures for defining childhood obesity. The aim of our study was to evaluate fat mass (FM, kg and %) measurements using TST and BIA (50 kHz) in a cohort of 6-year-old Italian children. A total of 228 southern Italian children (121 boys, 107 girls), randomly selected in nine local primary schools, were included in the study. The correlation between methods for measuring FM was calculated. Linear regression analysis showed a significant positive correlation between FM measured with BIA and BMI (r=0.92, p<0.001) and with TST (r=0.79, p<0.001). We conclude that FM measurement using TST and BIA is comparable in different BMI ranges. However, BIA is a useful and alternative method for detecting body composition in children and may be a more precise tool than TST for measuring FM in epidemiological studies in pediatric populations.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and is related to the fatty acid profile of the plasma membranes. The purpose of the present study was to investigate fatty acid composition and cholesterol content of cell membranes in patients with type 2 diabetes and, thus, to evaluate the possible factors leading to the alteration of plasma membrane fluidity. The study was performed in 20 healthy control subjects and 32 patients with type 2 diabetes. The fatty acid profiles and cholesterol content of the erythrocyte (RBC) and leukocyte (WBC) membranes were determined by a gas chromatographic method. When one considers the membrane constituents increasing fluidity and the ones decreasing it, the diabetics had a membrane composition decreasing fluidity compared to controls. On the other hand, when compared to control subjects, type 2 diabetic patients showed a significantly higher proportion of C16:0 components in erythrocyte and leukocyte membranes and plasma samples (25.4±3.1% vs. 31.1±4%; 23.3±2.4% vs. 29.3±5.2%; 27.6±3.9% vs. 34.5±5.7%; p<0.005, p<0.01 and p<0.005, respectively). Our results suggest that the ratio of saturated:unsaturated fatty acids changes in plasma and cell membranes of patients with type 2 diabetes. This situation may cause, at least in part, RBC–WBC function abnormalities and insulin resistance because of inconvenient membrane fluidity.

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000–1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005–2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000–1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.

The mechanism of potentiation of insulin secretion by fructose was investigated. Twenty mM fructose + 3 mM glucose stimulated insulin secretion in a biphasic manner similar to what is found during stimulation with 20 mM glucose, whereas 20 mM fructose alone did not affect secretion. Fructose utilization was measured as formation of tritiated water from 5-3H-fructose. At 27.8 mM fructose the utilization rate was 258 pmol/2 h/10 islets, which is less than the utilization rate of 2.8 mM glucose. 20 mM glucose increased the islet NADH/NAD+ and NADPH/-NADP+ redox ratios as well as islet concentration of ATP and PEP. 20 mM fructose + 3 mM glucose did not affect the concentration of ATP and PEP or the NADH/NAD+ redox ratio. The NADPH/NADP+ ratio was significantly decreased (60%) after 2.5 min incubation with 20 mM fructose + 3 mM glucose. It is concluded that fructose potentiation of insulin secretion is not primarily dependent on fructose metabolism and that any conceivable effect on plasma membrane ion fluxes as caused by a reduction of plasma membrane disulfides, may be caused by mechanisms other than a mere increase in the pyridine nucleotide substrates for the transhydrogenation process.

The aim of our study was to evaluate in 18 diabetic patients (11 with and 7 without evidence of autonomic neuropathy as revealed by common cardiovascular tests) alterations indicative of autonomic nervous involvement of the gastrointestinal tract, independently of the presence of suggestive symptoms. All patients, without evidence of obstructive or mucosal pathology of the upper gastrointestinal tract, underwent the following: 1) study of gastric emptying time of non-absorbable radiopaque markers (90, 120, 150 and 210 min); 2) study of gastric acid secretion: basal (BAO) and peak (PAO) acid output after sham-feeding (PAOSF) and peak acid output after pentagastrin (PAOPENT) · PAOSF/PAOPENT ratio is an index of vagal integrity; 3) esophageal manometry. Our data confirm that a delayed gastric emptying of undigestible solids is a frequent finding in diabetic subjects. This was highly significant (p<0.01) at 150 min after a standard meal, in patients with signs of autonomic neuropathy and was often associated with asymptomatic esophageal motor abnormalities. No correlation was found with index of vagal integrity, hormonal pattern and degree of glycemic control. Autonomic neuropathy cannot be considered the only explanation for gastric and esophageal abnormalities in decompensated diabetes.