The Burden of Obesity in Type 1 Diabetic Subjects: A Sex-specific Analysis From the AMD Annals Initiative.

OBJECTIVE: Obesity is a growing emergency in type 1 diabetes (T1D). Sex differences in obesity prevalence and its clinical consequences in adult T1D subjects have been poorly investigated. The aim of this study was to investigate the prevalence of obesity and severe obesity, clinical correlates, and potential sex differences in a large cohort of T1D subjects participating to the AMD (Associazione Medici Diabetologi) Annals Initiative in Italy. RESEARCH DESIGN AND METHODS: The prevalence of obesity [body mass index(BMI) ≥30 kg/m2] and severe obesity (BMI ≥ 35 kg/m2) according to sex and age, as well as obesity-associated clinical variables, long-term diabetes complications, pharmacological treatment, process indicators and outcomes, and overall quality of care (Q-score) were evaluated in 37 436 T1D subjects (45.3% women) attending 282 Italian diabetes clinics during 2019. RESULTS: Overall, the prevalence of obesity was similar in the 2 sexes (13.0% in men and 13.9% in women; mean age 50 years), and it increased with age, affecting 1 out of 6 subjects ages >65 years. Only severe obesity (BMI >35 kg/m2) was more prevalent among women, who showed a 45% higher risk of severe obesity, compared with men at multivariate analysis. Cardiovascular disease risk factors (lipid profile, glucose, and blood pressure control), and the overall quality of diabetes care were worse in obese subjects, with no major sex-related differences. Also, micro- and macrovascular complications were more frequent among obese than nonobese T1D men and women. CONCLUSIONS: Obesity is a frequent finding in T1D adult subjects, and it is associated with a higher burden of cardiovascular disease risk factors, micro- and macrovascular complications, and a lower quality of care, with no major sex differences. T1D women are at higher risk of severe obesity.

Breastfeeding during the COVID-19 pandemic: Suggestions on behalf of woman study group of AMD.

SARS-Cov2 infection has recently spread to Italy with important consequences on pregnancy management, mother and child health and mother-child contact. Breastfeeding improves the health of mother and child and reduces risk of neonatal infection with other pathogens that are likely to cause serious illness. To date no evidence confirmed COVID-19 vertical transmission from infected pregnant mother to their fetus. However it is well known that an infected mother can transmit the COVID-19 virus through respiratory droplets during breastfeeding or intimate contact. Thus, the mothers with known or suspected COVID-19 should adhere to standard and contact precautions during breastfeeding. Woman Study Group of AMD, after reviewing current knowledge about COVID-19 vertical transmission and the compatibility of breastfeeding in COVID-19 mother, the available recommendations from Health Care Organizations and main experts opinions, issued the following suggestions on breastfeeding during the COVID-19 pandemic, addressed both to mothers with and without diabetes. It should be considered that following suggestions may change in the future when more evidence is acquired regarding SARS-Cov2 infection.

Correlation between baseline characteristics and clinical outcomes in a large population of diabetes patients treated with liraglutide in a real-world setting in Italy.

PURPOSE: Treatment with liraglutide in randomized controlled trials is associated with significant reductions in glycated hemoglobin (HbA1c) and weight loss in type 2 diabetes patients. The aim of this retrospective observational study was to investigate correlations of glycemic control and weight outcomes with baseline characteristics of patients starting liraglutide in outpatient clinics in Italy. METHODS: Type 2 diabetes patients were followed from baseline to 4, 8, and 12 months. Changes in glycemic parameters, weight, blood pressure, and lipids were assessed. Subanalyses were performed according to baseline characteristics. Multivariate linear and logistic regressions were used to assess correlations between glycemic efficacy, weight reduction, and liraglutide discontinuation after 12 months and baseline characteristics. FINDINGS: Four hundred and eighty-one patients were included. Mean (SD) age at baseline was 57.3 (9.2) years, diabetes duration was 9.5 (6.8) years, weight was 106.7 (20.8) kg, body mass index (BMI; calculated as kg/m(2)) was 37.1 (6.6), HbA1c was 8.7% (1.3%), fasting plasma glucose was 168.5 (45.3) mg/dL; 38.2% were treated previously with insulin and 52.2% were treated with metformin alone. After 12 months, mean (SD) changes were HbA1c -1.2% (1.4%), fasting plasma glucose -28.3 (41.1) mg/dL, weight -3.5 (5.8) kg, BMI -1.3 (2.1), waist circumference -2.6 (6.7) cm (all, P < 0.001). Drop in weight and HbA1c did not differ between baseline BMI classes ≤30 or >30. Weight loss was unchanged among diabetes duration quartiles, and HbA1c reduction was significantly greater in patients with ≤4 years of diabetes duration (P = 0.01). Non-insulin-treated patients reached HbA1c ≤7% significantly more often than treated patients (44.2% vs 21.2%; odds ratio = 2.94; P < 0.001) and had significantly greater weight loss (-4.5 [8.2] kg vs -2.6 [5.4] kg; P = 0.03). Patients on metformin reached HbA1c target more frequently than others (43.1% vs 29.7%; odds ratio = 1.80; 95% CI, 1.05-3.07). Significant positive determinants for HbA1c reduction after 12 months were baseline HbA1c, age, and prior metformin monotherapy, and weight loss at 12 months was positively correlated with baseline weight, and negatively correlated with prior insulin treatment. Overall, 5.0% of patients interrupted liraglutide before the 12th month due to lack of glycemic control; they were less frequently treated with metformin only before liraglutide (29.2% vs 50.2%; P = 0.04). IMPLICATIONS: Treatment with liraglutide in a real-world setting is associated with low therapy failure, good glycemic response, weight loss, and improvement in systolic blood pressure and lipid profile. The HbA1c drop did not differ among baseline BMI classes, indicating that efficacy is maintained in patients with lower BMI. The probability of reaching HbA1c ≤7% was significantly higher in patients previously treated with metformin alone and without any previous insulin. This could reinforce the hypothesis that better results with liraglutide could be achieved in patients after early metformin failure.

Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women.

OBJECTIVE: In hyperandrogenic women, hyperinsulinaemia amplifies 17 α-hydroxycorticosteroid intermediate response to ACTH, without alterations in serum cortisol or androgen response to stimulation. The aim of the study is to assess whether acute hyperinsulinaemia determines absolute changes in either basal or ACTH-stimulated adrenal steroidogenesis in these subjects. DESIGN AND METHODS: Twelve young hyperandrogenic women were submitted in two separate days to an 8 h hyperinsulinaemic (80  mU/m² × min) euglycaemic clamp, and to an 8 h saline infusion. In the second half of both the protocols, a 4 h ACTH infusion (62.5  µg/h) was carried out. Serum cortisol, progesterone, 17 α-hydroxyprogesterone (17-OHP), 17 α-hydroxypregnenolone (17-OHPREG), DHEA and androstenedione were measured at basal level and during the protocols. Absolute adrenal hormone secretion was quantified by measuring C19 and C21 steroid metabolites in urine collected after the first 4 h of insulin or saline infusion, and subsequently after 4 h of concurrent ACTH infusion. RESULTS: During insulin infusion, ACTH-stimulated 17-OHPREG and 17-OHP were significantly higher than during saline infusion. No significant differences in cortisol and androgens response to ACTH were found between the protocols. Nevertheless, urinary excretion of ACTH-stimulated C19 and C21 steroid metabolites was significantly higher during hyperinsulinaemia than at basal insulin levels (both P < 0.005). Changes in steroid metabolites molar ratios suggested stimulation by insulin of 5 α-reductase activity. CONCLUSIONS: These in vivo data support the hypothesis that insulin acutely enhances ACTH effects on both the androgen and glucocorticoid pathways.

Combination treatment with metformin and glibenclamide versus single-drug therapies in type 2 diabetes mellitus: a randomized, double-blind, comparative study.

To compare efficacy and tolerability of combination treatment with metformin and sulfonylurea with each of these drugs alone in the treatment of type 2 diabetes, 88 type 2 diabetic subjects (hemoglobin A1c [HbA1c] levels, 8.0%+/-1.0%; age, 57.3+/-7.1 years; body mass index [BMI]. 27.0+/-2.6 kg/m2; diabetes duration, 9.8+/-8.2 years; means +/- SD) were randomly assigned to double-blind treatment with metformin (500 to 3,000 mg/d), glibenclamide (5 to 15 mg/d), or their combination (metformin 400 to 2,400 mg/d + glibenclamide 2.5 to 15 mg/d) for 6 months. Thereafter, groups were crossed over for the following 6 months. Thus, each patient received metformin or glibenclamide alone, and the combination treatment. Doses were titrated to obtain HbA1c levels < or = 6.0% and fasting plasma glucose levels less than 140 mg/dL. Eighty patients concluded both treatment periods and were included in the analysis of treatment efficacy. In patients receiving metformin or glibenclamide alone, the maximal dose was reached in 21 and 25 patients, respectively; 8 and 15 of these subjects, respectively, required the maximal dose when they were on the combination treatment. During the study, 4 (10.0%) subjects receiving metformin, 7 (17.1%) receiving glibenclamide, and 31 (39.2%) receiving the combination treatment reached HbA1c levels < or = 6.0%. Moreover, when efficacy of the combination treatment on glycemic control was compared with that of single-drug therapies in each individual patient, the combination was significantly more effective than either metformin or glibenclamide (HbA1c after treatment, 6.1%+/-1.1% v 7.3%+/-1.4%, and 6.5%+/-0.7% v 7.6%+/-1.5%, respectively, both P<.0001). In conclusion, combination treatment with metformin and sulfonylurea is more effective than these drugs alone in improving glycemic control in type 2 diabetes, while also allowing a reduction of the dosage of each drug.