Publications by authors named "Eric Renard"

150 Publications

Root cause determination of intraperitoneal catheter obstructions: Insulin amyloid aggregates vs foreign body reaction.

J Control Release 2021 Jun 10;336:1-15. Epub 2021 Jun 10.

Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Road U3092, Storrs, CT 06269, USA. Electronic address:

Continuous intraperitoneal insulin infusion, from an implanted insulin pump connected to a catheter that delivers insulin directly to the peritoneal cavity has many clinical advantages for patients with Type 1 diabetes. However, the ongoing incidence of catheter obstructions remains a barrier to the widespread use of this therapy. To date, the root cause of these obstructions remains unknown. Here, a two-year clinical investigation was conducted, along with the development of an animal model to enable a mechanistic investigation into this issue. This novel animal model was able to mimic the catheter obstructions that occur in patients and, fortuitously, at an accelerated rate. This model allowed for independent assessment of each potential cause associated with catheter obstructions to help identify the root cause. Both macroscopic and microscopic analysis were conducted with regards to the onset and progression of catheter obstructions, along with monitoring of insulin delivery. Interestingly, although insulin aggregation occurs in insulin pumps and insulin aggregates were found in some catheter obstructions, insulin is unlikely to be the root cause, since obstructions also occurred in the control groups where only diluent (no insulin) was administered to the animals. Inflammatory cells, different phenotypes of fibroblasts, as well as collagen were observed in all obstructed catheters explanted from the patients and the animals. The presence of these cells and collagen is indicative of a typical foreign body reaction. In addition, the dynamic change in the fibroblasts with respect to morphology, phenotype, and spatial distribution suggests that tissue irritation-mediated epithelial to mesenchymal transition plays a role in catheter obstructions.
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http://dx.doi.org/10.1016/j.jconrel.2021.06.005DOI Listing
June 2021

Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study.

Eur J Endocrinol 2021 Jul 5;185(2):299-311. Epub 2021 Jul 5.

Department of Endocrinology, Diabetology and Nutrition, Strasbourg University Hospitals, Strasbourg, France.

Objective: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.

Methods: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736).

Results: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only.

Conclusions: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.
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http://dx.doi.org/10.1530/EJE-21-0068DOI Listing
July 2021

Effects of Hormonal Contraception Use on Cognitive Functions in Patients With Bulimia Nervosa.

Front Psychiatry 2021 17;12:658182. Epub 2021 May 17.

Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, Montpellier, France.

Growing evidences indicate that sex hormones have an effect on cognitive functions, and that Bulimia Nervosa (BN) is associated with cognitive impairment. The aim of this study was to determine the effect of hormonal contraception (HC) use on four cognitive functions that are impaired in patients with BN. This retrospective exploratory study included 103 women with a diagnosis of BN based on the DSM-5 criteria. Their age ranged from 15 to 45 years, and 46.6% were taking HC (oral, transdermal, or intrauterine). Cognition was assessed with the d2 test (attention), Iowa gambling task (IGT; decision making), Brixton spatial anticipation test (set shifting), and Rey-Osterrieth complex figure test (central coherence). Data were analyzed with logistic regression models to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of HC effect on the neuropsychological test scores. In the multivariate model, HC use was significantly associated with better scores for two d2 test indices: F-score [OR = 0.98, 95% CI = (0.95; 0.99)] and final total score ratio [OR = 0.87, 95% CI = (0.77; 0.99)]. HC was also associated with a better understanding of the IGT explicit rules. No difference between the two groups (HC and non-HC use) was detected for set shifting and central coherence. This exploratory study suggests that HC could have effects on the sustained attention and concentration in women with BN. More studies are needed to confirm these results.
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http://dx.doi.org/10.3389/fpsyt.2021.658182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165222PMC
May 2021

No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed-loop system for 12 weeks: A post hoc secondary analysis of the multicentre, randomized controlled Diabeloop WP7 trial.

Diabetes Obes Metab 2021 May 19. Epub 2021 May 19.

Centre d'Etude et de Recherche pour l'Intensification du Traitement du Diabète (CERITD), Evry, France.

A post hoc analysis of the Diabeloop WP7 multicentre, randomized controlled trial was performed to investigate the efficacy of the Diabeloop Generation-1 (DBLG1) closed-loop system in controlling the hypoglycaemia induced by physical activity (PA) in real-life conditions. Glycaemic outcomes were compared between days with and without PA in 56 patients with type 1 diabetes (T1D) using DBLG1 for 12 weeks. After the patient announces a PA, DBLG1 reduces insulin delivery and, if necessary, calculates the amount of preventive carbohydrates (CHO). Daily time spent in the interstitial glucose range less than 70 mg/dL was not significantly different between days with and without PA (2.0% ± 1.5% vs. 2.2% ± 1.1%), regardless of the intensity or duration of the PA. Preventive CHO intake recommended by the system was significantly higher in days with PA (41.1 ± 35.5 vs. 21.8 ± 28.5 g/day; P < .0001), and insulin delivery was significantly lower (31.5 ± 10.5 vs. 34.0 ± 10.5 U/day; P < .0001). The time spent in hyperglycaemia and the glycaemic variation coefficient increased significantly on days with PA. In real-life conditions, the use of DBLG1 avoids PA-induced hypoglycaemia. Insulin adjustments and preventive CHO recommendation may explain this therapeutic benefit.
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http://dx.doi.org/10.1111/dom.14442DOI Listing
May 2021

A prospective cohort study of postpartum glucose metabolic disorders in early versus standard diagnosed gestational diabetes mellitus.

Sci Rep 2021 May 17;11(1):10430. Epub 2021 May 17.

Department of Endocrine and Metabolic Diseases, CHU Nimes, Univ Montpellier, Place du Professeur Debré, 30029, Nîmes Cedex 09, France.

Early gestational diabetes mellitus (eGDM) is diagnosed when fasting plasma glucose before 24 weeks of gestation (WG) is ≥ 5.1 mmol/L, whilst standard GDM is diagnosed between 24 and 28 WG by oral glucose tolerance test (OGTT). eGDM seems to have worse obstetric outcomes than standard GDM. We compared the rates of postpartum glucose metabolism disorders between women with early versus standard GDM in this prospective study on women with GDM from three university hospitals between 2014 and 2016. Patients were included if they were < 24 WG with at least one risk factor for GDM and excluded if they had type 2 diabetes. Patients were assigned to Group 1 (G1) for eGDM according to IADPSG: fasting blood glucose < 24 WG between 5.1 and 7 mmol/L. Group 2 (G2) consisted of patients presenting a standard GDM at 24-28 WG on OGTT results according to IADPSG: T0 ≥ 5.1 mmol/L or T60 ≥ 10.0 mmol g/L or T120 ≥ 8.5 mmol/L. The primary outcome was postpartum OGTT result. Five hundred patients were analysed, with 273 patients undergoing OGTT at 4-18 weeks postpartum: 192 patients in G1 (early) and 81 in G2 (standard). Patients in G1 experienced more insulin therapy during pregnancy than G2 (52.2% versus 32.5%, p < 0.001), but no patients were taking insulin postpartum in either group. G1 patients experienced less preterm labour (2.6% versus 9.1%, p = 0.043), more induced deliveries (38% versus 25%, p = 0.049) and reduced foetal complications (29.2% versus 42.0%, p = 0.048). There was no significant difference in the rate of postpartum glucose metabolism disorders (type 2 diabetes, impaired glucose tolerance, impaired fasting glycaemia) between groups: 48/192 (25%) in G1 and 17/81 (21%) in G2, p = 0.58. Thus the frequency of early postpartum glucose metabolism disorders is high, without difference between eGDM and standard GDM. This supports measurement of fasting plasma glucose before 24 WG and the threshold of 5.1 mmol/L seems appropriate until verification in future studies.Trial registration: NCT01839448, ClinicalTrials.gov on 22/04/2013.
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http://dx.doi.org/10.1038/s41598-021-89679-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128886PMC
May 2021

Modification of bone mineral density, bone geometry and volumetric BMD in young women with obesity.

Bone 2021 09 14;150:116005. Epub 2021 May 14.

Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHRU) Montpellier, Montpellier, France; PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France.

Background: Most obese women with low-trauma fractures present normal areal bone mineral density (aBMD), suggesting that other bone parameters are more determinant for fracture risk in these patients.

Objectives: (i) Determine the effects of obesity in young women on areal bone mineral density (aBMD), bone geometry, strength, and volumetric BMD determined by advanced DXA-based methods; (ii) model the profiles of bone parameters for each population with age; and (iii) determine the factors related to body composition (i.e. lean tissue mass and fat mass) potentially implicated in the "bone adaptation" in the femoral region.

Subjects And Methods: Two hundred and twenty adolescent and young women from 18 to 35 years old were enrolled in this study: 128 patients with obesity and 92 age-matched (±6 months) normal-weight controls. aBMD was determined with DXA, whereas hip geometry and strength parameters were assessed by hip structural analysis (HSA) and volumetric BMD by 3D-SHAPER® software.

Results: Compared with controls, subjects with obesity presented significantly higher aBMD at all bone sites, but the difference was greater at hip compared with lumbar spine or radius. Bone size estimates (i.e. cortical thickness), as well as strength estimates (i.e. cross-sectional area) were higher at all femoral subregions including femoral neck, intertrochanteric region and femoral shaft in young women with obesity. In whole proximal femur and all femoral compartments, vBMD was also higher in subjects with obesity, but the difference between groups was greater for cortical vBMD compared with trabecular vBMD. When hip bone parameters were modelled for each group from individual values, maximal values were reached between 20 and 26 years in both groups but, whatever the age, subjects with obesity presented higher values than controls. In both groups, lean body mass (LBM) was the parameter most positively associated with the greatest number of bone parameters studied.

Conclusion: Our study confirmed that young women with obesity presented higher aBMD, better hip geometry and greater strength compared with normal-weight controls. Additionally, cortical and trabecular compartments measured by 3D-SHAPER® were favourably and concomitantly modified. However, it remains to be demonstrated whether the evaluation of these new parameters would provide better prediction of fracture risk in this population than aBMD.
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http://dx.doi.org/10.1016/j.bone.2021.116005DOI Listing
September 2021

Ten-years outcomes of islet transplantation in patients with type 1 diabetes: data from the Swiss-French GRAGIL network.

Am J Transplant 2021 May 7. Epub 2021 May 7.

Department of Endocrinology, Grenoble University Hospital, Grenoble Alpes, Pôle DigiDune, Grenoble, France.

To describe the 10-year outcomes of islet transplantation within the Swiss-French GRAGIL Network, in patients with type 1 diabetes experiencing high glucose variability associated with severe hypoglycemia and/or with functional kidney graft. We conducted a retrospective analysis of all subjects transplanted in the GRAGIL-1c and GARGIL-2 islet transplantation trials and analyzed components of metabolic control, graft function and safety outcomes over the 10-year period of follow-up. Forty-four patients were included between September 2003 and April 2010. Thirty-one patients completed a ten-year follow-up. Ten years after islet transplantation, median HbA1c was 7.2% [6.2-8.0] (55 mmol/mol [44-64]) vs 8.0% [7.1-9.1] (64 mmol/mol [54-76]) before transplantation (p<0.001). 17/23 (73.9%) recipients were free of severe hypoglycemia, 1/21 patient (4.8%) was insulin-independent and median C-peptide was 0.6 ng/ml [0.2-1.2]. Insulin requirements (UI/kg/day) were 0.3 [0.1-0.5] vs 0.5 [0.4-0.6] before transplantation (p<0.001). Median [IQR] β-score was 1 [0-4] (p<0.05 when comparing with pre-transplantation values) and 51.9% recipients had a functional islet graft at 10 years. With a 10-year follow up in a multicentric network, islet transplantation provided sustained improvement of glycemic control and was efficient to prevent severe hypoglycemia in almost 75% of the recipients.
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http://dx.doi.org/10.1111/ajt.16637DOI Listing
May 2021

Patient-reported outcomes in adults with type 1 diabetes in global real-world clinical practice: The SAGE study.

Diabetes Obes Metab 2021 Aug 14;23(8):1892-1901. Epub 2021 Jun 14.

Medical Faculty, University Hospital of Freiburg, Freiburg, Germany.

Aims: To conduct a secondary analysis of the SAGE study to evaluate the association between glycaemic control and patient-reported outcomes (PROs), in adults with type 1 diabetes (T1DM) across different age groups and regions.

Materials And Methods: SAGE was a multinational, cross-sectional, observational study in adults with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and ≥65 years), and reported across different regions. PRO questionnaires were applied to assess hypoglycaemia fear (Hypoglycemia Fear Survey-II), diabetes-related distress (Problem Areas In Diabetes questionnaire), insulin treatment satisfaction (Insulin Treatment Satisfaction Questionnaire), and diabetes-specific quality of life (QoL; Audit of Diabetes-Dependent Quality of Life). Multivariable analysis was performed to evaluate the relationship between glycated haemoglobin (HbA1c) target achievement (<7% and individualised targets) with PRO scores.

Results: The PRO scores showed relatively low levels of diabetes-related emotional distress and fear of hypoglycaemia, moderate to high treatment satisfaction, and low diabetes-related impact on QoL. Results were generally comparable across age groups with some regional variability. Achievement of the HbA1c <7% target was associated with less worry about hypoglycaemia, lower diabetes-related emotional distress, higher insulin treatment satisfaction, and higher QoL. Achievement of individualised HbA1c targets was associated with lower diabetes-related emotional distress and higher insulin treatment satisfaction.

Conclusions: Better glycaemic control was most closely associated with low emotional distress due to diabetes and high patient-reported insulin treatment satisfaction.
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http://dx.doi.org/10.1111/dom.14416DOI Listing
August 2021

Patient-reported outcomes in adults with type 1 diabetes in global real-world clinical practice: The SAGE study.

Diabetes Obes Metab 2021 Aug 14;23(8):1892-1901. Epub 2021 Jun 14.

Medical Faculty, University Hospital of Freiburg, Freiburg, Germany.

Aims: To conduct a secondary analysis of the SAGE study to evaluate the association between glycaemic control and patient-reported outcomes (PROs), in adults with type 1 diabetes (T1DM) across different age groups and regions.

Materials And Methods: SAGE was a multinational, cross-sectional, observational study in adults with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and ≥65 years), and reported across different regions. PRO questionnaires were applied to assess hypoglycaemia fear (Hypoglycemia Fear Survey-II), diabetes-related distress (Problem Areas In Diabetes questionnaire), insulin treatment satisfaction (Insulin Treatment Satisfaction Questionnaire), and diabetes-specific quality of life (QoL; Audit of Diabetes-Dependent Quality of Life). Multivariable analysis was performed to evaluate the relationship between glycated haemoglobin (HbA1c) target achievement (<7% and individualised targets) with PRO scores.

Results: The PRO scores showed relatively low levels of diabetes-related emotional distress and fear of hypoglycaemia, moderate to high treatment satisfaction, and low diabetes-related impact on QoL. Results were generally comparable across age groups with some regional variability. Achievement of the HbA1c <7% target was associated with less worry about hypoglycaemia, lower diabetes-related emotional distress, higher insulin treatment satisfaction, and higher QoL. Achievement of individualised HbA1c targets was associated with lower diabetes-related emotional distress and higher insulin treatment satisfaction.

Conclusions: Better glycaemic control was most closely associated with low emotional distress due to diabetes and high patient-reported insulin treatment satisfaction.
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http://dx.doi.org/10.1111/dom.14416DOI Listing
August 2021

Hypoglycaemia detection and prediction techniques: A systematic review on the latest developments.

Diabetes Metab Res Rev 2021 Mar 15:e3449. Epub 2021 Mar 15.

Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, Montpellier, France.

The main objective of diabetes control is to correct hyperglycaemia while avoiding hypoglycaemia, especially in insulin-treated patients. Fear of hypoglycaemia is a hurdle to effective correction of hyperglycaemia because it promotes under-dosing of insulin. Strategies to minimise hypoglycaemia include education and training for improved hypoglycaemia awareness and the development of technologies to allow their early detection and thus minimise their occurrence. Patients with impaired hypoglycaemia awareness would benefit the most from these technologies. The purpose of this systematic review is to review currently available or in-development technologies that support detection of hypoglycaemia or hypoglycaemia risk, and identify gaps in the research. Nanomaterial use in sensors is a promising strategy to increase the accuracy of continuous glucose monitoring devices for low glucose values. Hypoglycaemia is associated with changes on vital signs, so electrocardiogram and encephalogram could also be used to detect hypoglycaemia. Accuracy improvements through multivariable measures can make already marketed galvanic skin response devices a good noninvasive alternative. Breath volatile organic compounds can be detected by dogs and devices and alert patients at hypoglycaemia onset, while near-infrared spectroscopy can also be used as a hypoglycaemia alarms. Finally, one of the main directions of research are deep learning algorithms to analyse continuous glucose monitoring data and provide earlier and more accurate prediction of hypoglycaemia. Current developments for early identification of hypoglycaemia risk combine improvements of available 'needle-type' enzymatic glucose sensors and noninvasive alternatives. Patient usability will be essential to demonstrate to allow their implementation for daily use in diabetes management.
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http://dx.doi.org/10.1002/dmrr.3449DOI Listing
March 2021

The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.

Arch Osteoporos 2021 01 14;16(1):13. Epub 2021 Jan 14.

Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHRU) Montpellier, 34295, Montpellier, France.

This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients.

Purpose: The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN).

Methods: Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel.

Results: BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm vs 0.806 ± 0.010 g/cm), lumbar spine (0.966 ± 0.012 g/cm vs 0.886 ± 0.010 g/cm), and radius (0.545 ± 0.005 g/cm vs 0.526 ± 0.04 g/cm) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification.

Conclusion: BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.
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http://dx.doi.org/10.1007/s11657-020-00870-wDOI Listing
January 2021

The SAGE study: Global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM.

Diabetes Metab Res Rev 2020 Dec 28:e3430. Epub 2020 Dec 28.

Diabetes Department, University Hospitals of Derby and Burton, Derby, UK.

Aims: To describe glycaemic control and diabetes management in adults with type 1 diabetes (T1DM), in a real-life global setting.

Materials And Methods: Study of Adults' GlycEmia (SAGE) was a multinational, multicentre, single visit, noninterventional, cross-sectional study in adult patients with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64 and ≥65 years) and reported across different regions. The primary endpoint was the proportion of participants achieving HbA  less than 7.0 % in each age group. Secondary endpoints included incidence of hypoglycaemia, severe hypoglycaemia and severe hyperglycaemia leading to diabetic ketoacidosis (DKA) and therapeutic management of T1DM.

Results: Of 3903 included participants, 3858 (98.8%) were eligible for the study. Overall, 24.3% (95% confidence interval [CI]: 22.9-25.6) of participants achieved the glycaemic target of HbA  less than 7.0 %, with more participants achieving this target in the 26-44 years group (27.6% [95% CI: 25.5-29.8]). Target achievement was highest in Eastern and Western Europe, and lowest in the Middle East. The incidence of hypoglycaemia and of severe hyperglycaemia leading to DKA tended to decrease with age, and varied across regions. Age and regional differences were observed in therapeutic management, including types of device/insulin usage, frequency of insulin dose adjustment and technology usage.

Conclusions: Glycaemic control remains poor in adults with T1DM globally. Several areas of treatment may be optimised to improve outcomes, including supporting patient self-management of insulin therapy, increasing use of technologies such as CGM, and greater provision of healthcare support.
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http://dx.doi.org/10.1002/dmrr.3430DOI Listing
December 2020

LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells.

Eur J Endocrinol 2021 Jan;184(1):155-168

Sorbonne Université, Inserm UMRS_938, Centre de Recherche Saint Antoine, Paris, France.

Objective: The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants.

Methods: A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue.

Results: We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction.

Conslusions: Biallelic LIPE null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target.
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http://dx.doi.org/10.1530/EJE-20-1013DOI Listing
January 2021

Assessment of the effect of pregnancy planning in women with type 1 diabetes treated by insulin pump.

Acta Diabetol 2021 Mar 24;58(3):355-362. Epub 2020 Oct 24.

Department of Endocrinology, Diabetes and Nutrition, Montpellier University Hospital, Montpellier, France.

Background: Pregnant women with type 1 diabetes (T1D) have high risk of complications despite improved care based on technology advancements.

Objective: To assess the effects of pregnancy planning on fetal and maternal outcomes in T1D women treated with continuous subcutaneous insulin infusion (CSII).

Study Design: We retrospectively assessed maternal and neonatal outcomes in T1D women using CSII who had planned or unplanned pregnancies between 2002 and 2018. The study was done in two European countries with similar sustained programs for pregnancy planning over the study period.

Results: Data from 107 pregnancies and newborn babies were collected. Seventy-nine pregnancies (73.8%) had been planned. HbA1c was lower in planned versus unplanned pregnancy before and during all three trimesters of pregnancy (p < 0.0001). Pregnancy planning was associated with a reduction in the occurrence of iatrogenic preterm delivery (RR 0.44, 95% CI 0.23-0.95; p = 0.01). Risk reduction persisted after adjustments for mother's age above 40 years and preeclampsia. High HbA1c before or during pregnancy was associated with an increased risk of iatrogenic preterm delivery (RR 3.05, 95% CI 1.78-5.22, p < 0.0001). Premature newborns needed intensive care more often than those at term (RR 3.10, 95% CI 1.53-4.31; p = 0.002).

Conclusions: Pregnancy planning in T1D women using CSII was associated with better glucose control and decreased risk of iatrogenic preterm delivery. Hence preconception care also improves pregnancy outcome in patients using an advanced mode of insulin delivery. Planned pregnancies could further benefit from the use of new metrics of glucose control.
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http://dx.doi.org/10.1007/s00592-020-01620-7DOI Listing
March 2021

The Impact of Retrospective Childhood Maltreatment on Eating Disorders as Mediated by Food Addiction: A Cross-Sectional Study.

Nutrients 2020 Sep 28;12(10). Epub 2020 Sep 28.

PSNREC, University of Montpellier, INSERM, CHU de Montpellier, 34295 Montpellier, France.

Background: The current study aimed to test whether food addiction (FA) might mediate the relationship between the presence of a history of childhood maltreatment and eating disorder (ED) symptom severity.

Methods: Participants were 231 patients with ED presenting between May 2017 and January 2020 to a daycare treatment facility for assessment and management with mainly the Eating Disorder Inventory-2 (EDI-2), the Child Trauma Questionnaire (CTQ), and the Yale Food Addiction Scale (YFAS 2.0).

Results: Participants had a median age of 24 (interquartile range (IQR) 20-33) years and manifested anorexia nervosa (61.47%), bulimia nervosa (16.88%), binge-eating disorders (9.09%), and other types of ED (12.55%). They were grouped into those likely presenting FA ( = 154) and those without FA ( = 77). The group with FA reported higher scores on all five CTQ subscales, as well as the total score of the EDI-2 ( < 0.001). Using mediation analysis; significant indirect pathways between all CTQ subscales and the EDI-2 total score emerged via FA, with the largest indirect effect emerging for physical neglect (standardized effect = 0.208; 95% confidence interval (CI) 0.127-0.29) followed by emotional abuse (standardized effect = 0.183; 95% CI 0.109-0.262).

Conclusion: These results are compatible with a model in which certain types of childhood maltreatment, especially physical neglect, may induce, maintain, and/or exacerbate ED symptoms via FA which may guide future treatments.
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http://dx.doi.org/10.3390/nu12102969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601309PMC
September 2020

Primary care visits can reduce the risk of potentially avoidable hospitalizations among persons with diabetes in France.

Eur J Public Health 2020 12;30(6):1056-1061

Health Services Research Unit, Public Health Department (DIM), CHU Montpellier, Montpellier, France.

Background: Diabetes is a frequent chronic condition, which can lead to costly complications if not managed well in the primary care setting. Potentially avoidable hospitalizations (PAH) are considered as an indirect measure of primary care. However, the association between primary care use and PAH in diabetic patients has not been investigated in France.

Methods: We investigate the association between primary care indicators and PAH at an individual level among persons with diabetes in a population-based cohort study on the French national health insurance database (EGB sample). PAH occurrence in 2013 was modeled as a function of primary care use and access, health status and socio-economic indicators over the exposure period 2011-12 using a cause-specific hazards model with death as a competing event.

Results: We included 25 293 diabetics in our cohort, among which 385 (1.5%) experienced at least 1 PAH in 2013. After adjustment on health status indicators, primary care use had a protective effect against PAH. Diabetic patients who had seen a general practitioner (GP) 10-14 times had a reduced hazard of PAH compared to less frequent encounters (HR=0.49, P<0.001). The effect size decreased when the number of encounters increased, suggesting a remaining confounding effect of health status.

Conclusions: For the first time in France, this study shows a protective effect of the number of GP encounters against PAH at an individual level and highlights the importance of a frequent monitoring of diabetic patients in the primary care setting to prevent PAH occurrence.
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http://dx.doi.org/10.1093/eurpub/ckaa137DOI Listing
December 2020

The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study.

J Clin Med 2020 Jul 21;9(7). Epub 2020 Jul 21.

Montpellier School of Medicine, University of Montpellier, 34000 Montpellier, France.

Background: The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic.

Methods: Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients' clinical courses.

Results: Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course ( < 0.01 and = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L.

Conclusions: Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.
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http://dx.doi.org/10.3390/jcm9072315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408691PMC
July 2020

Personal Experience With COVID-19 and Diabetes in the South of France: Technology Facilitates the Management of Diabetes in Disruptive Times.

Authors:
Eric Renard

J Diabetes Sci Technol 2020 Jul 19;14(4):772-773. Epub 2020 May 19.

Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, France.

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http://dx.doi.org/10.1177/1932296820929370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673169PMC
July 2020

Correction to: InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring-Study Design.

Diabetes Ther 2020 Jul;11(7):1607-1608

International Diabetes Center at Park Nicollet, Minneapolis, USA.

In the original publication, the timing of baseline CGM assessment was incorrectly stated in the text in two instances; it is correct in Fig. 1.
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http://dx.doi.org/10.1007/s13300-020-00820-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324444PMC
July 2020

Practical recommendations for the management of diabetes in patients with COVID-19.

Lancet Diabetes Endocrinol 2020 06 23;8(6):546-550. Epub 2020 Apr 23.

Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital Carl Gustav Carus, Dresden, Germany; Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland; Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Deutsche Forschungsgemeinschaft-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.
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http://dx.doi.org/10.1016/S2213-8587(20)30152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013PMC
June 2020

Practical recommendations for the management of diabetes in patients with COVID-19.

Lancet Diabetes Endocrinol 2020 06 23;8(6):546-550. Epub 2020 Apr 23.

Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital Carl Gustav Carus, Dresden, Germany; Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland; Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Deutsche Forschungsgemeinschaft-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.
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http://dx.doi.org/10.1016/S2213-8587(20)30152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013PMC
June 2020

InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring-Study Design.

Diabetes Ther 2020 Apr 25;11(4):1017-1027. Epub 2020 Feb 25.

International Diabetes Center at Park Nicollet, Minneapolis, USA.

Introduction: Suboptimal glycaemic control among people with type 1 diabetes (T1D) is known to lead to long-term micro- and macrovascular complications and, unfortunately, it is still prevalent even in the most affluent societies. Although glycated haemoglobin monitoring is considered to be the gold standard for assessing glycaemic control, such monitoring is unable to reliably measure acute glycaemic excursions. Continuous glucose monitoring (CGM) has been shown to improve glucose control and reduce the incidence of hypoglycaemia, and also allow a more complete assessment of overall glycaemic control and hyper- and hypoglycaemic excursions. The use of CGM has led to time-in-range, which is the time that a patient is within the glycaemic range of 70 to 180 mg/dL, to be adopted as a treatment target. To date, only limited data comparing the second-generation insulins glargine 300 U/mL (Gla-300) and degludec 100 U/mL (IDeg-100) in people with T1D are available, and there is no CGM literature on comparisons of the use of CGM results to assess primary, secondary and tertiary endpoints. The aim of the InRange study was to address this unmet need.

Methods: InRange is a multicentre, randomised, active-controlled, parallel-group, 12-week, open-label, phase 4, comparative study. Adults with T1D will be randomised to receive once-daily Gla-300 or IDeg-100 by subcutaneous injection in the morning. Following an 8-week titration period, CGM data will be collected over 20 consecutive days.

Planned Outcomes: The primary objective is to demonstrate that Gla-300 is noninferior to IDeg-100 in terms of glycaemic control [time-in-range ≥ 70 to ≤ 180 mg/dL (≥ 3.9 to ≤ 10 mmol/L)] and variability, as assessed using CGM, in adults with T1D. The results are expected to help confirm the utility of CGM in clinical practice in this population and provide insight into its application as an outcome measure in clinical practice.

Trial Registration: NCT04075513.
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http://dx.doi.org/10.1007/s13300-020-00781-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136362PMC
April 2020

Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent?

Diabetes Care 2020 04 27;43(4):821-827. Epub 2020 Jan 27.

Diabetes Research Group, Cymru, Swansea University, Swansea, Wales, U.K.

Objective: To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes.

Research Design And Methods: People with type 1 diabetes ( = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.9, 3.45, and 3.0 mmol/L).

Results: MDG was significantly higher, and %CV significantly lower (both < 0.001), when comparing the 24-h glycemic profiles according to whether no time or a certain duration of time was spent below the thresholds. Univariate regression analyses showed that MDG and %CV were the two explanatory variables that entered the model with the outcome variable (time spent below the thresholds). The classification and regression tree procedure indicated that the predominant predictor for hypoglycemia was %CV when the threshold was 3.0 mmol/L. In people with mean glucose ≤7.8 mmol/L, the time spent below 3.0 mmol/L was shortest ( < 0.001) when %CV was below 34%.

Conclusions: In type 1 diabetes, short-term glycemic variability relative to mean glucose (i.e., %CV) explains more hypoglycemia than does mean glucose alone when the glucose threshold is 3.0 mmol/L. Minimizing the risk of hypoglycemia requires a %CV below 34%.
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http://dx.doi.org/10.2337/dc19-1549DOI Listing
April 2020

Certified Interoperability Allows a More Secure Move to the Artificial Pancreas Through a New Concept: "Make-It-Yourself".

Authors:
Eric Renard

J Diabetes Sci Technol 2020 03 20;14(2):195-197. Epub 2020 Jan 20.

Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, France.

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http://dx.doi.org/10.1177/1932296820901612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196868PMC
March 2020

Specific Effects of Anorexia Nervosa and Obesity on Bone Mineral Density and Bone Turnover in Young Women.

J Clin Endocrinol Metab 2020 04;105(4)

Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHRU) Montpellier, Montpellier, France.

Objective: The threefold aim was to (1) compare areal bone mineral density (aBMD), bone turnover markers, and periostin levels in young women with either anorexia nervosa (AN) or obesity (OB) and controls (CON); (2) model the profiles according to age; and (3) determine the parameters associated with aBMD.

Subjects And Methods: One hundred and fifty-two young women with ages ranging from 16.0 to 27.0 years were subdivided into 3 groups (AN, OB, CON). The CON group was age-matched by ±6 months. aBMD, bone turnover markers, and periostin levels were evaluated.

Results: aBMD modeling showed that hip aBMD was higher in OB than in the other 2 groups from 19 years, and AN presented lower values than CON from 21 years. aBMD at the lumbar spine was higher in older OB and CON women, starting from 20 to 22 years, but in AN the difference with the other 2 groups increased with age. Periostin levels were lower in OB than in AN or CON, but no variation with age was observed. Compared with controls, OB and AN presented similarly lower markers of bone formation, although markers of bone resorption were lower in OB and higher in AN. A modeling approach showed that markers of bone formation and resorption were lower in older than in younger CON, whereas the values of these bone markers remained relatively constant in AN and OB. In all groups, lean body mass (LBM) was the parameter most positively correlated with aBMD.

Conclusion: This study demonstrated that weight extremes (AN or OB) influence aBMD, bone remodeling and periostin profiles. Moreover, factors related to aBMD were specific to each condition, but LBM was the parameter most consistently associated with aBMD.
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http://dx.doi.org/10.1210/clinem/dgz259DOI Listing
April 2020

The Differential and Combined Action of Insulin Glargine and Lixisenatide on the Fasting and Postprandial Components of Glucose Control.

J Diabetes Sci Technol 2021 Mar 6;15(2):371-376. Epub 2019 Dec 6.

Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA.

Background: iGlarLixi is an injectable combination of long acting insulin glargine (iGlar) and glucagon-like peptide 1 receptor agonist lixisenatide in a fixed ratio, which was proven safe and effective for the treatment of type 2 diabetes. Lixisenatide and iGlar act differently on fasting and postprandial plasma glucose (fasting plasma glucose [FPG] and postprandial glucose [PPG]). Here, we deconstruct quantitatively their respective FPG and PPG effects.

Method: This post hoc study analyzes data from the Lixilan-O trial, where 1170 subjects with type 2 diabetes were randomly assigned to 30 weeks of once daily injections of lixisenatide, iGlar, and iGlarLixi (1:2:2). The FPG and PPG components of glucose control were assessed in terms of mean glucose (fasting mean plasma glucose [FMPG] and prandial mean plasma glucose [PMPG], respectively). The MPGP was computed across all meals as a delta between post- and premeal glucose; glucose variability was measured by the high blood glucose index (HBGI) (fasting HBGI and prandial HBGI [PHBGI], respectively), and glycemic exposure measured by area under the curve (AUC) computed overall. All metrics were derived from seven-point self-monitoring glucose profiles.

Results: Insulin glargine lowered significantly FMPG by 15.3 mg/dL ( < .01) without any significant change in PMPG. Lixisenatide, when added to iGlar, reduced PMPG by 9.7 mg/dL ( < .01), AUC by 96.3 mg∙h/dL ( < .01), and PHBGI by 2.4 ( < .01), primarily due to attenuation of PPG and without significant change in mean FPG.

Conclusion: Insulin glargine and lixisenatide act selectively on FPG and PPG. Their combination iGlarLixi offers more effective glucose control than its components due to the cumulative effect on FPG and PPG, which is evidenced by reduced average glycemia, glycemic exposure, and glucose variability.
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http://dx.doi.org/10.1177/1932296819891170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256059PMC
March 2021

The Differential and Combined Action of Insulin Glargine and Lixisenatide on the Fasting and Postprandial Components of Glucose Control.

J Diabetes Sci Technol 2021 Mar 6;15(2):371-376. Epub 2019 Dec 6.

Center for Diabetes Technology, University of Virginia, Charlottesville, VA, USA.

Background: iGlarLixi is an injectable combination of long acting insulin glargine (iGlar) and glucagon-like peptide 1 receptor agonist lixisenatide in a fixed ratio, which was proven safe and effective for the treatment of type 2 diabetes. Lixisenatide and iGlar act differently on fasting and postprandial plasma glucose (fasting plasma glucose [FPG] and postprandial glucose [PPG]). Here, we deconstruct quantitatively their respective FPG and PPG effects.

Method: This post hoc study analyzes data from the Lixilan-O trial, where 1170 subjects with type 2 diabetes were randomly assigned to 30 weeks of once daily injections of lixisenatide, iGlar, and iGlarLixi (1:2:2). The FPG and PPG components of glucose control were assessed in terms of mean glucose (fasting mean plasma glucose [FMPG] and prandial mean plasma glucose [PMPG], respectively). The MPGP was computed across all meals as a delta between post- and premeal glucose; glucose variability was measured by the high blood glucose index (HBGI) (fasting HBGI and prandial HBGI [PHBGI], respectively), and glycemic exposure measured by area under the curve (AUC) computed overall. All metrics were derived from seven-point self-monitoring glucose profiles.

Results: Insulin glargine lowered significantly FMPG by 15.3 mg/dL ( < .01) without any significant change in PMPG. Lixisenatide, when added to iGlar, reduced PMPG by 9.7 mg/dL ( < .01), AUC by 96.3 mg∙h/dL ( < .01), and PHBGI by 2.4 ( < .01), primarily due to attenuation of PPG and without significant change in mean FPG.

Conclusion: Insulin glargine and lixisenatide act selectively on FPG and PPG. Their combination iGlarLixi offers more effective glucose control than its components due to the cumulative effect on FPG and PPG, which is evidenced by reduced average glycemia, glycemic exposure, and glucose variability.
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http://dx.doi.org/10.1177/1932296819891170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256059PMC
March 2021
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