Assisted reproductive technology, risk of gestational diabetes, and perinatal outcomes in singleton pregnancies.

AIMS: To evaluate the impact of assisted reproductive technology (ART) on the risk of gestational diabetes mellitus (GDM) in single pregnancies. MATERIALS AND METHODS: We retrospectively collected clinical and anthropometric data of 219ART- and 256 age- and body mass index (BMI)-matched women with spontaneous conception screened for GDM. The primary outcome was to evaluate GDM prevalence in ART women. RESULTS: There were no differences in age, BMI, and family history of diabetes in the two groups of women. ART-women were more frequently primiparous, whereas the prevalence of previous GDM was higher in SC-women. The prevalence of GDM in the whole cohort was 36.1% and was higher in ART-women (52.3% vs. 23.4%; p < 0.0001). In the whole cohort, on multivariate analysis, family history of diabetes (OR 1.67; 95% CI: 1.03-2.69), previous GDM (OR 7.05; 95% CI: 2.92-17.04), pre-pregnancy obesity (OR 2.72; 95% CI 1.21-6.13), and ART (OR 4.14; 95% CI 2.65-6.48) were independent risk factors for GDM. Among ART-women, age over 40 years was associated with GDM. Preterm delivery was more common in ART-women; gestational week at delivery, birth weight, ponderal index, and Apgar score were lower in ART-women than in SC-women, both in the whole cohort and in GDM women. CONCLUSIONS: Among women undergoing ART treatment, at least one in two develops GDM. ART appears to be an independent risk factor for GDM in single pregnancies, particularly above the age of 40. ART treatment seems to be associated with an increased rate of preterm delivery and lower neonatal birth weight and Apgar score, especially in GDM women. CLINICAL TRIAL REGISTRATION: The study was not registered as it is an observational retrospective evaluation.

Higher Prevalence of Cancer in Patients with Diabetic Foot Syndrome.

Background: Diabetes mellitus (DM) is associated with a higher prevalence of many forms of cancer. Diabetic foot syndrome (DFS) is associated with higher risk of lower limb amputation and mortality not all explainable with a cardiovascular profile at greater risk compared with DM patients without DFS. DFS could be associated with an increasing cancer incidence. To explore a possible link between DFS and cancer, comparing two cohorts of patients (DFS+ and DFS-) with a cohort of superimposable non-DM controls. Methods: We retrospectively analysed the databases of our department for all consecutive patients admitted between January 2019 and December 2021, selecting all DM pts, and sorting DFS+ pts, admitted for foot complications, from DFS- ones, admitted for other reasons. Cases of pancreatic cancer as well as cancer-related admissions were excluded. Patients were compared to non-DM patients admitted for non-oncological medical problems. The primary endpoint was to compare the prevalence of cancer among the groups, while the secondary endpoint was to look for predictors for cancer in the groups studied. Results: A cohort of 445 consecutive DM inpatients (222 DFS+ and 223 DFS-) and 255 controls were studied. Cancer prevalence in DFS+ group was significantly higher than in DFS- (p = 0.008) and controls (p = 0.031), while no differences were observed between DFS- and the controls. Univariate regression analysis showed a significant association between cancer and DFS (p = 0.007), age at admission (p ≤ 0.001), years of diabetes (p = 0.017) and haemoglobin concentration [Hb] (p = 0.030). In the multivariate regression analysis with DFS, age at admission and [Hb], only DFS (p = 0.021) and age at admission (p ≤ 0.001) persisted as independent factors associated with cancer. Conclusions: A higher prevalence of cancer in DFS+ patients than in DFS- patients and non-diabetic controls is reported. DFS and age can both be considered independent predictors of cancer in patients with DM.

ß-Cell Function, Incretin Effect, and Glucose Kinetics in Response to a Mixed Meal in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin.

OBJECTIVE: To explore the complementary effects of a combination of dipeptidyl peptidase 4 and sodium-glucose cotransporter 2 inhibitors added to metformin on hormonal and metabolic responses to meal ingestion. RESEARCH DESIGN AND METHODS: Forty-five patients (age 58 ± 8 years; HbA1c 58 ± 6 mmol/mol; BMI 30.7 ± 3.2 kg/m2) with type 2 diabetes uncontrolled with metformin were evaluated at baseline and 3 and 28 days after 5 mg saxagliptin (SAXA), 10 mg dapagliflozin (DAPA), or 5 mg saxagliptin plus 10 mg dapagliflozin (SAXA+DAPA) using a mixed-meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion, and sensitivity. RESULTS: At day 3, fasting and mean MMTT glucose levels were lower with SAXA+DAPA (-31.1 ± 1.6 and -91.5 ± 12.4 mg/dL) than with SAXA (-7.1 ± 2.1 and -53 ± 10.5 mg/dL) or DAPA (-17.0 ± 1.1 and -42.6 ± 10.0 mg/dL, respectively; P < 0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA +3%) and insulin sensitivity (+2.2 ± 1.7, +0.4 ± 0.7, and +0.4 ± 0.4 mg ⋅ kg-1⋅ min-1, respectively) improved with SAXA+DAPA (P < 0.007). Mean glucagon-like peptide 1 (GLP-1) was higher with SAXA+DAPA than with SAXA or DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting endogenous glucose production (EGP) increased with SAXA+DAPA and DAPA. During MMTT, EGP suppression was greater (48%) with SAXA+DAPA (vs. SAXA 44%; P = 0.02 or DAPA 34%; P = 0.2). Metabolic clearance rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, ß-cell glucose sensitivity, and insulin sensitivity had further increased in the SAXA+DAPA group (P = 0.02), with no additional changes in GLP-1, glucagon, fasting or MMTT EGP, or MCRglu. CONCLUSIONS: SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA, with improved ß-cell function, insulin sensitivity, GLP-1 availability, and glucose clearance.

Effects of Intermittent Fasting on Brain Metabolism.

We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations in neurons, which, overall, enhance cellular stress resistance, synaptic plasticity, and neurogenesis. Still, the absence of guidelines regarding the application of IF to patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge on the different IF protocols and long-term effects of IF on brain metabolism before it can be widely prescribed.

Risk factors associated with postpartum impaired glucose regulation in women with previous gestational diabetes.

AIMS: For women with previous gestational diabetes (GDM), international guidelines recommend 75 g oral glucose tolerance test (OGTT) at 4-12 weeks after delivery to assess glucose tolerance, considering their increased risk of type 2 diabetes. We evaluated prevalence of postpartum impaired glucose regulation (IGR) and identified associated risk factors. METHODS: We retrospectively collected data from 749 women with previous GDM (IADPSG criteria) who underwent postpartum OGTT for type 2 diabetes screening between 2011 and 2019. IGR was identified according to ADA criteria. RESULTS: Prevalence of IGR was 12.7%, lower in women with pre-pregnancy normal weight, higher in women with family history of type 2 diabetes and in those treated with insulin during pregnancy. Prevalence of IGR raised with increasing number of altered glucose values at OGTT performed during pregnancy for GDM screening. HbA1c and triglycerides measured during the third trimester of pregnancy were higher in women with postpartum IGR. At postpartum screening, women with IGR had higher BMI, waist, blood pressure. At multivariate logistic regression analysis, family history of diabetes (OR 2.21; 95% CI: 1.33-3.69; p < 0.01) and presence of all three glucose values exceeding threshold at OGTT during pregnancy (OR 2.89; 95% CI: 1.42-5.86; p < 0.01) were independently associated with IGR. CONCLUSIONS: In women with GDM, persistence of IGR in the immediate postpartum period is associated with family history of diabetes and the presence of all three glucose values exceeding diagnostic threshold for GDM at OGTT in pregnancy, suggesting that these women should undergo specific diabetes monitoring and prevention programs.

Effect of Vitamin D Supplementation on Obesity-Induced Insulin Resistance: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: The aim was to investigate whether vitamin D supplementation, combined with a hypocaloric diet, could have an independent effect on insulin sensitivity in subjects with both overweight and hypovitaminosis D. Changes from baseline in anthropometric parameters, body composition, glucose tolerance, and insulin secretion were considered as secondary outcomes. METHODS: Eighteen volunteers who were nondiabetic and vitamin D deficient and had BMI > 25 kg/m2 were randomized (1:1) in a double-blind manner to a hypocaloric diet + either oral cholecalciferol at 25,000 IU/wk or placebo for 3 months. Hyperinsulinemic-euglycemic clamp to measure insulin sensitivity was performed at baseline and after intervention. RESULTS: Body weight in both groups decreased significantly (-7.5% in the vitamin D group and -10% in the placebo group; P < 0.05 for both), with no between-group differences. Serum 25-hydroxyvitamin D levels in the vitamin D group increased considerably (from 36.7 ± 13.2 nmol/L to 74.8 ± 18.7 nmol/L; P < 0.001). Insulin sensitivity in the vitamin D group improved (from 4.6 ± 2.0 to 6.9 ± 3.3 mg·kg-1 ·min-1 ; P < 0.001), whereas no changes were observed in the placebo group (from 4.9 ± 1.1 to 5.1 ± 0.3 mg·kg-1 ·min-1 ; P = 0.84). CONCLUSIONS: Cholecalciferol supplementation, combined with a weight loss program, significantly improves insulin sensitivity in healthy subjects with obesity and might represent a personalized approach for insulin-resistant subjects with obesity.