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Combining basal insulin (BI) with glucagon-like peptide-1 receptor agonist (GLP-1RA) is recognized as a relevant option to optimize glucose control in type 2 diabetes (T2D). The EASY real-world study aimed to evaluate the modalities of initiation and the effectiveness of the insulin Degludec plus Liraglutide (IDegLira) fixed-ratio combination in the French health care system.A retrospective analysis included all patients with T2D and prior injectable therapy (GLP1-RA and/or insulin) who started treatment with IDegLira from September 2016 to December 2017 in 11 French diabetes centers. Baseline characteristics, reasons for IDegLira initiation, and modes of implementation were collected from the medical records. Changes in HbAIDegLira was initiated in 629 patients previously treated with GLP-1RA alone (11.6%), insulin alone (31.5% including 16.5% with BI and 14.9% with multiple daily injections [MDI]) or a free combination of GLP-1RA and insulin (56.9% including 44.8% with BI and 12.1% with MDI), associated or not with oral agents. IDegLira starting dose (mean of 29 ± 11 dose steps) most often exceeded the recommended dose, and was significantly correlated with prior BI but not GLP-1RA dosage. At initiation, mean age, body mass index (BMI) and HbAWhile providing new information on the use of IDegLira in the French healthcare system, these data confirm the effectiveness of this fixed-ratio combination in the management of T2D.

International audience; Aims: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromestreated with metreleptin in a national reference network, in a real-life setting.Patients and Methods: Clinical and metabolic data from patients receiving metreleptin in France wereretrospectively collected, at baseline, one year and at the latest follow-up during treatment.Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD, n=28) andpartial lipodystrophy (PLD, n=19) received metreleptin over the last decade. At baseline, age was 29.3[16.6-47.6] (years, median [interquartile range]); BMI 23.8 kg/m2 [21.2-25.7]; serum leptin 3.2 [1.0-4.9] ng/mL); 94% of patients had diabetes (66% insulin-treated), 53% hypertension, and 87%dyslipidemia. Metreleptin therapy, administered during 31.7 [14.2-76.0] months, was ongoing in 77%of patients at the latest follow-up. In patients with GLD, HbA1c (%) and fasting triglycerides (mmol/L)significantly decreased from baseline to one year-metreleptin treatment, from 8.4 [6.5-9.9] to 6.8 [5.6-7.4], and 3.6 [1.7-8.5] to 2.2 [1.1-3.7] respectively (p

OBJECTIVE Bone biopsy (BB) performed by a surgeon or an interventional radiologist is recommended for suspicion of osteomyelitis underlying diabetic foot ulcer (DFU). To facilitate its practice, we developed a procedure allowing bedside blind bone biopsy (B4) by a diabetologist. RESEARCH DESIGN AND METHODS We conducted a three-step observational study consisting of a feasibility and safety phase (phase 1) to assess the success and side effects of B4, a validity phase (phase 2) to compare DFU outcomes between positive (B4+) and negative (B4−) bone cultures, and a performance phase (phase 3) to compare B4 with the conventional surgical or radiological procedure basic bone biopsy (B3). Primary end points were the presence of bone tissue (phase 1) and complete DFU healing with exclusive medical treatment at 12 months (phases 2 and 3). RESULTS In phase 1, 37 consecutive patients with clinical and/or radiological suspicion of DFU osteomyelitis underwent B4. Bone tissue was collected in all patients with few side effects. In phase 2, a B4+ bone culture was found in 40 of 79 (50.6%) participants. Among B4+ patients, complete wound healing after treatment was 57.5%. No statistical difference was observed with patients with B4− bone culture not treated with antibiotics (71.8%, P = 0.18). In phase 3, the proportion of patients with positive BB was lower in B4 (40 of 79, 50.6%) than in B3 (34 of 44, 77.3%, P < 0.01). However, complete healing was similar (64.6% vs. 54.6%, P = 0.28). No difference in rate of culture contamination was observed. CONCLUSIONS B4 is a simple, safe, and efficient procedure for the diagnosis of DFU osteomyelitis with a similar proportion of healing to conventional BB.

The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

Objective A real-world, randomized study assessing the impact of a new, personalized, pharmacist-led text messaging service for managing type 2 diabetes (T2D). Methods Messages were tailored to patient’s needs based on their disease management habits, propensity for reactance, and physical activity levels at baseline. Treatment adherence (assed using the Morisky Medication Adherence Scale, MMAS-8, questionnaire), clinical factors (body mass index and physical activity) and biological markers for T2D were compared between patients who received a text message daily for 3 months in addition to standard care (SMS group) and those who received standard care alone (control group). Results 114 pharmacies recruited 499 patients. Greater increases in global MMAS-8 scores were observed after 3 months for the SMS group than for the control group, however, this improvement was not sustained after the text messages stopped. Body mass index was found to improve with the text messaging service. Conclusion This study indicated that personalized text messages provided by community pharmacists can have an impact on adherence levels among T2D patients. Practice implications Pharmacy-led innovations, such as text messaging services, could be used to accompany patients in their treatment and to improve patient understanding of their illness between healthcare appointments.

To determine the prevalence of diabetic retinopathy (DR) and its risk factors in adult type 1 diabetes (T1D) patients METHODS: In this cross-sectional study, all T1D patients followed in the University Center for Diabetes and its Complications of Lariboisière Hospital (Paris, France) between January 2017 and February 2019 were included. Ophthalmologic and systemic data were collected from electronic records. The association between DR (and each grade) and associated factors were estimated by univariate and multivariate analyses using logistic regression models.A total of 1464 patients (46.2% of women, mean age: 42.2 ± 15.8 years) were included. The mean hemoglobin A1c (HbA1c) was 7.8 ± 1.7% and the mean diabetes duration was 20.5 ± 13.5 years. DR prevalence was 50.1% (47.4-52.6) and the prevalence of mild, moderate, and severe non-proliferative DR and proliferative DR was 19.1%, 9.4%, 3.9%, and 17.6%, respectively. DR was significantly associated with male gender, an older age, former and current smoking status, a higher BMI, the presence of nephropathy and neuropathy, higher HBA1c, and longer diabetes duration. Patients with HbA1c 10% had an adjusted odds ratio (OR) of 3.25 (1.77-6.01) of having DR compared to patients with HbA1c 6.5%. Patients with a diabetes duration 30 years had an adjusted OR of 24.87 (14.82-42.67) higher of having DR compared to patients with a diabetes duration 10 years.In this study, 50.1% of adult T1D patients had DR and 17.6% had proliferative DR. Diabetes duration and HbA1c were major risk factors.

Background Type 1 diabetes is associated with accelerated vascular aging and advanced atherosclerosis resulting in increased rates of cardiovascular disease and premature death. We evaluated associations between Leukocyte telomere length (LTL), allelic variations (SNPs) in LTL-related genes and the incidence of coronary heart disease (CHD) in adults with long-standing type 1 diabetes. Methods We assessed associations of LTL, measured at baseline by RT–PCR, and of SNPs in 11 LTL-related genes with the risk of coronary heart disease (CHD: myocardial infarction or coronary revascularization) and all-cause death during follow-up in two multicenter French-Belgian prospective cohorts of people with long-standing type 1 diabetes. Results In logistic and Cox analyses, the lowest tertile of LTL distribution (short telomeres) at baseline was associated with the prevalence of myocardial infarction at baseline and with increased risk of CHD (Hazard ratio 3.14 (1.39–7.70), p = 0.005, for shorter vs longer tertile of LTL) and all-cause death (Hazard ratio 1.63 (95% CI 1.04–2.55), p = 0.03, for shorter vs combined intermediate and longer tertiles of LTL) during follow-up. Allelic variations in six genes related to telomere biology (TERC, NAF1, TERT, TNKS, MEN1 and BICD1) were also associated with the incidence of CHD during follow-up. The associations were independent of sex, age, duration of diabetes, and a range of relevant confounding factors at baseline. Conclusions Our results suggest that short LTL is an independent risk factor for CHD in people with type 1 diabetes.

Context Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. Objective To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. Design Setting and Participants We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. Main Outcome Measure(s) The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. Results Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those 80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in Conclusions Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

Background A high prevalence of pulmonary embolism (PE) has been described during COVID‐19. Our aim was to identify predictive factors of PE in non‐ICU hospitalized COVID‐19 patients. Methods Data and outcomes were collected upon admission during a French multicenter retrospective study, including patients hospitalized for COVID‐19, with a CT pulmonary angiography (CTPA) performed in the emergency department for suspected PE. Predictive factors significantly associated with PE were identified through a multivariate regression model. Results A total of 88 patients (median [IQR] age of 68 years [60‐78]) were analyzed. Based on CTPA, 47 (53.4%) patients were diagnosed with PE, and 41 were not. D‐dimer ≥3000 ng/mL (OR 8.2 [95% CI] 1.3‐74.2, sensitivity (Se) 0.84, specificity (Sp) 0.78, P = .03), white blood count (WBC) ≥12.0 G/L (29.5 [2.3‐1221.2], Se 0.47, Sp 0.92, P = .02), and ferritin ≥480 µg/L (17.0 [1.7‐553.3], Se 0.96, Sp 0.44, P = .03) were independently associated with the PE diagnosis. The presence of the double criterion D‐dimer ≥3000 ng/mL and WBC ≥12.0 G/L was greatly associated with PE (OR 21.4 [4.0‐397.9], P = .004). Conclusion The white blood count, the D‐dimer and ferritin levels could be used as an indication for CTPA to confirm PE on admission in non‐ICU COVID‐19 patients.

In patients (pts) with diabetes mellitus (DM) , Covid-pneumonia mortality rate >20% has been reported. A low fixed dose of intravenous dexamethasone (Dx) for days (RECOVERY study, 6 mg/d, i.e 0.5 mg/kg/d prednisone equivalent) has been shown to effectively reduce Covid-pneumonia mortality. In an observational study, prognosis was improved with an oral combination of prednisone fixed dose (1mg/kg/d) , direct anticoagulant/aspirin/colchicine/furosemide (DOAACF) . We hypothesized prednisone tailored doses driven by clinical evolution (extra 1mg/kg/d for every increase of O2 flow) added-on DOAACF for days would decrease morbi-mortality. In our monocentric, retrospective study (03.2020-05.2021) , pts with Covid-pneumonia requiring O2 out of the Intensive Care Unit (ICU) were included. According to the Physicians discretionary caring decisions, a control group (no corticoid) , a Dx group, an oral tailored prednisone ≥1mg/kg/d-DOAACF group were compared. The primary endpoint was Day 28 ICU requirement or mortality. Out of 3pts included for hypoxemic Covid-pneumonia, 132 pts had DM (43%) (control n = 28; Dx n = 46; tailored prednisone-DOAACF n = 58) : median age 69y; Males/Females 2.8; BMI 28 kg/m2; cardiovascular history 40%; median SpO2 at room air 92%; median maximal O2 flow 4L/min. Pts characteristics were non statistically different. Prednisone median dose (1.5mg/kg/d) and aspirin-colchicine-furosemide use were significantly higher in the tailored prednisone-DOAACF group in which events rate (12%) was significantly lower (control 50%, p = 0.0003, Dx 37%, p = 0.004) . In the tailored group, no statistical difference observed with pts without DM (13.3%, p = 1) . Out of the ICU, in pts with DM, a five oral drugs combination made of tailored prednisone ≥1mg/kg/d, anti-inflammatory, antithrombotics, diuretic improves hypoxemic Covid-pneumonia prognosis. A randomized trial is needed. Disclosure J.Kevorkian: None. B.Mégarbane: None. F.Féron: None. J.Riveline: None. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical. J.Gautier: Other Relationship; Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company.

In patients with type 2 diabetes (T2D) , studies on nonalcoholic steatohepatitis (NASH) and hepatic fibrosis have been hindered by the constraints of histopathological diagnosis. We assessed the prevalence of, and features associated with, histologically proven NASH and fibrosis in a large group of T2D patients routinely screened for nonalcoholic fatty liver disease (NAFLD) .T2D outpatients with suspected NAFLD at their annual workup (based on ultrasound and liver function test results) were prospectively referred to an hepatologist. Patients with persistently elevated ALT (> 20 IU/L in females or > 30 IU/L in males) and no other causes for liver disease were proposed liver biopsy. Histological lesions were blindly analyzed by a single expert pathologist. Between October 2018 and March 2021, among 1,159 T2D patients screened, NASH and advanced fibrosis were found in 58% and 38% of 330 patients with adequate liver biopsy, respectively. Sequential use of FIB-4 and liver stiffness to rule in/out advanced fibrosis according to EASL algorithm, resulted in a 27% rate of false negative results in patients with FIB-4 1.3 and liver stiffness >8 kPa. Hypertension, waist circumference, triglycerides, aspartate aminotransferase, serum albumin and creatinine, were independently associated with NASH (AUROC 0.81 (95% CI 0.76-0.86)) . Waist circumference, gamma-glutamyl transpeptidase, FIB-4 and HDL cholesterol were independently associated with advanced fibrosis (AUROC 0.77 (0.72-0.83)) . Vascular complications of T2D were not associated with liver lesions. In conclusion, more than half of T2D patients with NAFLD displayed severe hepatic injuries. Liver lesions were independently associated with metabolic syndrome, but not with complications of T2D. Screening for NASH and advanced fibrosis should be part of regular workup of T2D patients. Models based on easily available variables may be useful. Disclosure J.Gautier: Other Relationship; Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company. H.Bihan: Other Relationship; Vitalair. J.Julla: Consultant; Sanofi. E.Larger: None. S.Pol: Board Member; AbbVie Inc., Gilead Sciences, Inc., Novo Nordisk. P.Bedossa: None. C.Laouenan: None. D.C.Valla: Advisory Panel; Intercept Pharmaceuticals, Inc. L.Castera: Advisory Panel; Alexion Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Speaker's Bureau; Novo Nordisk. T.Vidal-trecan: None. V.Paradis: Consultant; Inventiva Pharma, Servier Laboratories. T.Poynard: Stock/Shareholder; Biopredictive. S.Czernichow: Consultant; Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Lilly, Novo Nordisk. B.Terris: None. P.Manchon: None. D.Roulot: Consultant; AbbVie Inc., Gilead Sciences, Inc. Funding Agence Nationale pour la Recherche (ANR-17-T171105J)

Backgrounds and Aims: Leukocyte telomere length (LTL) is associated with cardiovascular risk. We evaluated associations between LTL, allelic variations (SNPs) in LTL-related genes (associated with LTL in the literature) and the incidence of coronary artery disease (CAD) in adults with long-standing type 1 diabetes. Participants and Methods: LTL was measured by real-time PCR in 260 participants of the GENEDIAB cohort (males 60%, age 45±12 years, duration of diabetes 29±years at baseline, mean±SD) . Thirty-three SNPs in LTL-associated genes were genotyped in 826 participants from GENEDIAB and GENESIS cohorts (males 55%, age 43±12 years, duration of diabetes 27±9 years at baseline) . The risk for CAD (myocardial infarction or coronary artery revascularization) during follow-up was analyzed using Cox models according to LTL (expressed in tertiles of distribution) and SNPs. Results: The cumulative incidence of CAD in GENEDIAB (11±7-year follow-up) was 21.2%. The incidence of CAD by LTL tertiles was 27.6% (shorter LTL) , 23.3% (intermediate LTL) and 12.6% (longer LTL) . Hazard ratio (HR) for shorter vs. longer LTL was 1.63 (95%CI 1.15-2.37) , p=0.005, unadjusted model, and 1.58 (95%CI 1.08-2.39) , p=0.02, after adjustment on sex, age, duration of diabetes, blood pressure, kidney function and history of CAD at baseline. The cumulative incidence of CAD in GENEDIAB and GENESIS pooled data (followed by 11±6 years) was 15.1%. Six SNPs located in three genes (TERC, NAF1 and TNKS) were significantly associated with the incidence of CAD. Discussion: Shorter LTL at baseline was associated with an increased risk of CAD during the follow-up in adults with long-standing type 1 diabetes. Allelic variations in LTL-related genes were also associated with coronary risk in these subjects. Disclosure M.Sanchez: None. G.Velho: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi. N.Venteclef: None. F.Fumeron: None. A.Scheen: Advisory Panel; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. J.Gautier: Other Relationship; Novo Nordisk, Sanofi, Speaker's Bureau; Eli Lilly and Company. M.Marre: Board Member; AstraZeneca, Consultant; Novo Nordisk. R.Roussel: None. K.Mohammedi: Board Member; Lilly, Novo Nordisk, Sanofi, Research Support; Cyclerion Therapeutics, Inc., Speaker's Bureau; Abbott, AstraZeneca.

Background Cardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin. Methods Included were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated. Results Using LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2. Conclusion Our results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.

International audience; A unimorph piezoelectric cantilever equipped with an Acoustic Black Hole (ABH) termination is designed for broadband energy harvesting. The ABH termination, with its tapered region, induces a focusing of the flexural vibrations which can be used to increase the efficiency of an energy harvesting device. A modal-based analytical model is presented, providing an explicit form of the electro-mechanical coupling for each beam eigenmode. Closed-form expressions for the coupled mechanical response and electrical outputs are obtained, allowing one to draw out a complete parametric study to optimize the device. The optimization procedure is conducted following two steps: first, optimal location and dimensions of a single piezoelectric patch are achieved by maximizing the modal electro-mechanical coupling factor (MEMCF) for each structural mode. Thanks to the proposed analytical approach, it is clearly shown that by putting the piezoelectric patch at the maximum of the strain field in the tapered termination, and by adjusting its length in accordance with the focalization created by the ABH effect, the ABH cantilever produces much higher MEMCFs over a wide frequency range and thus outperforms those of a uniform beam. Second, optimization of the shunted circuit is comprehensively performed for a circuit with only resistance, or both resistance and inductance, in series or in parallel. Analytical results show that the key design rule resides in matching the time scale of the circuit with that of the forcing frequency. Addition of the inductance allows enhancing the performance, but on a narrow frequency band. Finally, broadband advantages can be further obtained by considering multiple piezoelectric patches, in which the optimum is obtained when the shunted circuit in each patch is tuned targeting an eigenmode of the ABH beam.

Summary Background One of the unmet needs in patients with type 2 diabetes mellitus (T2DM) is the prediction of non‐alcoholic liver disease by non‐invasive blood tests, for each of the three main histological features, fibrosis, non‐alcoholic steatohepatitis (NASH) and steatosis. Aims To validate externally the performances of a recent panel, Nash‐FibroTest, for the assessment of the severity of fibrosis stages, NASH grades and steatosis grades. Methods We prospectively analysed 272 patients with T2DM. Standard definitions of stages and grades were used, and analyses were centralised and blinded. The performances of the FibroTest, NashTest‐2 and SteatoTest‐2 were assessed using the Obuchowski measure (OM), the main outcome recommended as a summary measure of accuracy includeing all pairwise stages and grades comparisons, which is not provided par the extensively used binary area under the ROC curve. Results The diagnostic performance of each component of the panel was significant. OM (SE; significance) of the FibroTest, the NashTest‐2 and the SteatoTest‐2 was 0.862 (0.012; P, From a single blood sample, the Nash FibroTest panel provides non‐invasive diagnosis of the stages of fibrosis and the grades of NASH, including ballooning and lobular inflammation, and steatosis grades in patients with type 2 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Objective High glucocorticoid levels in rodents inhibit development of beta cells during fetal life and lead to insulin deficiency in adulthood. To test whether similar phenomena occur in humans, we compared beta-cell function in adults who were exposed to glucocorticoids during the first part of fetal life with that of nonexposed subjects. Research Design and Methods The study was conducted in 16 adult participants exposed to glucocorticoids during the first part of fetal life and in 16 nonexposed healthy participants with normal glucose tolerance who were matched for age, sex, and body mass index (BMI). Exposed participants had been born to mothers who were treated with dexamethasone 1 to 1.5 mg/day from the sixth gestational week (GW) to prevent genital virilization in children at risk of 21-hydroxylase deficiency. We selected offspring of mothers who stopped dexamethasone before the 18th GW following negative genotyping of the fetus. Insulin and glucagon secretion were measured during an oral glucose tolerance test (OGTT) and graded intravenous (IV) glucose and arginine tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic-clamp. Results Age, BMI, and anthropometric characteristics were similar in the 2 groups. Insulinogenic index during OGTT and insulin sensitivity during the clamp were similar in the 2 groups. In exposed subjects, insulin secretion during graded IV glucose infusion and after arginine administration decreased by 17% (P = 0.02) and 22% (P = 0.002), respectively, while glucagon secretion after arginine increased. Conclusion Overexposure to glucocorticoids during the first part of fetal life is associated with lower insulin secretion at adult age, which may lead to abnormal glucose tolerance later in life.

Context Studies suggest that menopausal hormone therapy (MHT) prevents type 2 diabetes (T2D). The combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is an MHT that improves obesity and T2D in preclinical models of menopausal metabolic syndrome. The effect of CE/BZA on adiposity and glucose homeostasis in obese postmenopausal women is unknown. Objective To investigate the effect of CE/BZA on body composition, glucose homeostasis, and markers of inflammation in obese postmenopausal women. Research Design, Intervention, and Participants Randomized, double-blind, placebo-controlled pilot trial of 12 obese menopausal women assigned to 12-week treatment with CE 0.45 mg/BZA 20 mg (n = 7) or placebo (n = 5). At baseline and after 12 weeks, we assessed body composition (dual-energy X-ray absorptiometry), glucose homeostasis (IV glucose tolerance test), and inflammation biomarkers. Results Women treated with CE/BZA exhibited increased β cell function using homeostatic model assessment-B [median (interquartile range) CE/BZA vs placebo: 18.5 (−0.9 to 320.6) μU/mM vs −25.5 (−39.9 to −0.1) μU/mM; P = 0.045], and decreased basal glucose concentrations (Gb) [−5.2 (−9.2 to −1.7) mg/dL vs 2.7 (0.9 to 4.9) mg/dL; P = 0.029]. Insulin sensitivity was higher in the placebo arm [1.35 (1.12 to 1.82) (μU/mL) min−1 vs −0.24 (−1.50 to 0.19) (μU/mL) min−1; P = 0.029]. No changes between treatment groups were observed for the acute insulin response to glucose (AIRg), the disposition index (DI), body composition, and inflammatory biomarkers. Conclusions A 12-week treatment of obese postmenopausal women with CEs/BZA improves fasting β cell function and glucose concentrations without change in AIRg, HOMA-IR, DI, body composition, or markers of inflammation.

International audience