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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.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mardi 3 avril 2018

Diabetes & Metabolism - Sous presse. Manuscrit accepte. Disponible en ligne depuis le jeudi 21 mai 2020

Aim To investigate whether diabetic micro- and macrovascular complications (mMVC) influence cancer-related events in people with type 2 diabetes. Methods People with type 2 diabetes from the SURDIAGENE cohort were characterized (duration of diabetes, HbA1c, mMVC, history of cancer) and prospectively followed-up for death and cancer-related events (occurrence, dissemination and cancer-related death). Results Between 2002 and 2012, 1468 participants (58% men, mean age 64.8 ± 10.7 years, mean duration of diabetes 14.5 ± 9.9 years at baseline) were enrolled. At baseline, 119 (8%) had a personal history of cancer. Incident cancer occurred in 207 (14%) patients during a mean follow-up of 7.3 ± 3.7 years and was associated with older age, smoking status and personal history of cancer. mMVC were not associated with cancer-related events, considering cancer occurrence, node/metastasis dissemination and cancer-specific death. Risk of all-cause mortality was increased in diabetic patients cumulating cancer history and mMVC (HR 1.73, 95%CI 1.25-2.38) compared to those with neither cancer nor mMVC. In our cohort, cancer-related death was not associated with mMVC (HR 1.05, 95%CI 0.67-1.64), but conversely history of cancer was significantly associated with cardiovascular-related death (HR 2.41, 95%CI 1.36-4.26). Conclusion In our cohort, mMVC were not associated with cancer-related events, while history of cancer was significantly associated with cardiovascular death.

Background Our study aimed to compare the clinical outcomes of patients with and without diabetes admitted to hospital with COVID-19. Methods This retrospective multicentre cohort study comprised 24 tertiary medical centres in France, and included 2851 patients (675 with diabetes) hospitalized for COVID-19 between 26 February and 20 April 2020. A propensity score-matching (PSM) method (1:1 matching including patients’ characteristics, medical history, vital statistics and laboratory results) was used to compare patients with and without diabetes (n = 603 per group). The primary outcome was admission to an intensive care unit (ICU) and/or in-hospital death. Results After PSM, all baseline characteristics were well balanced between those with and without diabetes: mean age was 71.2 years; 61.8% were male; and mean BMI was 29 kg/m2. A history of cardiovascular, chronic kidney and chronic obstructive pulmonary diseases were found in 32.8%, 22.1% and 6.4% of participants, respectively. The risk of experiencing the primary outcome was similar in patients with or without diabetes [hazard ratio (HR): 1.16, 95% confidence interval (CI): 0.95–1.41; P = 0.14], and was 1.29 (95% CI: 0.97–1.69) for in-hospital death, 1.26 (95% CI: 0.9–1.72) for death with no transfer to an ICU and 1.14 (95% CI: 0.88–1.47) with transfer to an ICU. Conclusion In this retrospective study cohort of patients hospitalized for COVID-19, diabetes was not significantly associated with a higher risk of severe outcomes after PSM. Trial registration number NCT04344327.

The outbreak of COVID-19 led to an unprecedented inflow of hospitalised patients with severe acute respiratory syndrome (SARS), requiring high-flow non-invasive oxygenation, if not invasive mechanical ventilation. While the best option in terms of non-invasive systems of oxygen delivery is still a matter of debate, it also remains unclear as to whether or not the optimal in-bed positioning of patients might also help to improve their oxygen saturation levels. On the basis of three representative cases, it is possible to propose the following hypotheses: (i) how patients are positioned has a strong influence on their oxygen saturation levels; (ii) saturation-optimalised positions are patient-specific; (iii) prone positions require ergonomic devices; and (iv) saturation-optimalised positions should aim to place the most affected part(s) of the lung(s) on top. Considered together, these hypotheses have led us to recommend that COVID-19 patients should undergo a specific assessment at admission to determine their saturation-optimalised in-bed position. However, further studies are still needed to assess the benefits of such a strategy on clinical outcomes.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 22 septembre 2016

Type 2 diabetes (T2D) is a complex, progressive disease with life-threatening complications and one of the most serious public-health problems worldwide. The two main mechanisms of T2D pathogenesis are pancreatic beta cell dysfunction and insulin resistance. It is now recognized that pancreatic beta cell dysfunction is a necessary factor for T2D development. Traditional therapies for controlling blood glucose are suboptimal as they fail to meet target goals for many patients. Glucagon-like peptide-1 receptor agonists (GLP1RA) and dipeptidyl peptidase-4 inhibitors (DPP4I) are an attractive class of therapy because they reduce blood glucose by targeting the incretin hormone system and, in particular, have the potential to positively affect pancreatic beta cell biology. This review outlines our current understanding of pancreatic beta cell incretin system dysfunction in T2D and summarizes recent evidence of the effect of incretin-based therapies on beta cell function and mass. Incretin-based therapies have shown strong evidence for beneficial effects on beta cell function and mass in animal studies. In humans, incretin-based therapies are effective glucose-lowering agents, but further study is still required to evaluate their long-term effects on beta cell function and safety as well as beta cell mass expansion.

Aim This report is an overview of type 2 diabetes (DT2) in the North African immigrant population living in France. Methods Data were collected in two separate cross-sectional national surveys. DT2 prevalence was estimated using a population-based survey involving 13 959 people aged ≥ 45 years (EDS), while health status and quality of care were evaluated using a sample of 3894 DT2 patients (ENTRED). Results Prevalence of DT2 and obesity was 14.0% [CI 95%: 9.9; 18.0] and 20.5% [15.7; 25.3], respectively, in participants born in North Africa (BNA) and 7.5% [7.0; 8.0] and 15.8% [14.7; 16.8], respectively, in those born in France (BIF). DT2 was associated with region of birth in women after adjusting for age, body mass index and income or occupation, but not after adjusting for education level. In men, DT2 was not associated with region of birth. BNA and BIF patients with diabetes frequently benefited from free medical coverage (88% vs. 84%, respectively), although BNA diabetic patients visited a general practitioner less frequently than BIF (8.5 vs. 9.0 visits/year, respectively). The percentage of BNA vs. BIF diabetes patients tested three times a year for HbA 1c was lower (39% vs. 44%), while HbA 1c was higher in BNA vs. BIF diabetics (> 8%: 30% vs. 15%). Ophthalmological complications were also more frequent in BNA vs. BIF patients with diabetes (25% vs. 18%, respectively). Conclusion The greater prevalence of DT2 in BNA women and the poorer glycaemic control observed in the BNA population overall both probably contribute to disparity in diabetes mortality compared with BIF diabetics, a fact that has been observed in previous studies.

Aim Epidemiological data suggest that glucose-6-phosphate dehydrogenase (G6PD) deficiency may be a risk factor for diabetes. Also, the occurrence of haemolysis in the context of diabetes crises has been reported in patients with G6PD deficiency. A unifying hypothesis could explain these associations. Methods We report two patients in whom haemolytic crises occurred soon after acute diabetes decompensation, and revealed G6PD deficiency. We have reviewed the mechanisms that may link the two diseases. Results One patient was admitted for decompensated ketosis-prone type-2 diabetes (KPT2D), but no acidosis, and was treated with insulin, then metformin and glibenclamide. The second patient had type-1 diabetes and ketoacidosis treated with insulin. Haemolytic crises were recognized 8 and 4 days after admission, respectively, and G6PD deficiency was confirmed in both patients. These patients and the other published cases share, as a unique characteristic, the occurrence of haemolysis after diabetes decompensation, whatever the treatment or associated conditions. Experimental data show that hyperglycaemia can reduce expression of the G6PD gene and activity of the enzyme. Conversely, G6PD deficiency can promote oxidative stress and impairment of insulin secretion by beta cells. Conclusion In patients at risk of G6PD deficiency, the possibility of haemolysis should be explored in case of diabetes crisis. In African patients with KPT2D diabetes, potentially oxidative hypoglycaemic agents should be avoided in the remission phase of the disease. G6PD deficiency and diabetes can aggravate each other, and diabetes could be aetiologically associated with G6PD deficiency.

Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. While insulin replacement represents the current therapy for type 1 diabetes, its metabolic control remains difficult, as exogenous insulin cannot exactly mimic the physiology of insulin secretion. Pancreatic or islet transplantation can provide exogenous insulin independence, but is limited by its intrinsic complications and the scarcity of organ donors. In this context, stem cell therapy, based on the generation of insulin-producing cells (IPCs) derived from MSCs, represents an attractive possibility. In this review, we provide a brief characterization of MSC immunomodulatory effects, and present the current experimental evidence for the potential therapeutic efficacy of MSC transplantation in diabetes.

The liver plays a pivotal role in energy metabolism. Under the control of hormones, especially insulin, the liver stores or releases glucose as needed by the body's systems. It is also responsible for an important part of non-esterified fatty-acid and aminoacid metabolism. Assessing hepatic insulin resistance is almost always synonymous with measuring hepatic glucose production (HGP) and calculating indices of hepatic insulin resistance. The most frequently used method to this end is the isotope dilution technique using a tracer. Among tracers, stable isotope-labelled glucose molecules are particularly advantageous over radioactive isotope-labelled glucose and are, therefore, the tracers of choice. The tracer is infused either on its own after an overnight fast to evaluate fasting HGP, or with some among the usual insulin-sensitivity tests to assess HGP suppression by insulin and/or glucose. In a fasting state, HGP is easily calculated whereas, during insulin or glucose infusion, some formula are needed to correct for the non-steady-state condition. The hepatic insulin-resistance index is the product of HGP and the corresponding plasma insulin concentration. Although subject to error, the isotope dilution method nevertheless remains an irreplaceable tool for assessing hepatic insulin resistance in clinical research. From a practical point of view, some easily obtainable indices and clinical or biochemical parameters can serve as surrogates or markers of hepatic insulin resistance in clinical practice. Finally, drugs such as metformin or glitazones can improve hepatic insulin resistance, hence their use in hepatic insulin-resistant states such as type 2 diabetes and non-alcoholic fatty liver disease.

Summary A new method is now available to measure capillary levels of 3hydroxybutyrate (3HB), one of the three ketone bodies. It is a quantitative and enzymatic test that uses the same equipment as for home capillary blood glucose determination but with specific strips. In comparison to urine ketone test, there is no false negative or false positive results, it is highly correlate to standard automate assays and patients find it more acceptable. Clinical implementations of this new test begin to be reported. Some studies showed an advantage of ketonemia versus ketonuria measurement to detect and to treat diabetic ketoacidosis in the emergency room. In diabetic patients treated with continuous subcutaneous insulin infusion, ketonemia seems to be more relevant to detect lack of insulin. In the current care of patient with type 1 diabetes and especially in children blood ketone test is more effective than urine ketone test to prevent hospitalisation during sick days. For other situations such as diabetic pregnancy or type 2 diabetes, more data are needed to determine if capillary measurement of 3HB is really useful. This new test is easier and less unpleasant than doing urinary test but it is still far more expensive. Further clinical studies are needed to define whether self 3HB monitoring should substitute urinary test in outpatient care.

Incretin hormones are defined as intestinal hormones released in response to nutrient ingestion, which potentiate the glucose-induced insulin response. In humans, the incretin effect is mainly caused by two peptide hormones, glucose-dependent insulin releasing polypeptide GIP, and glucagon-like peptide-1 GLP-1. GIP is secreted by K cells from the upper small intestine while GLP-1 is mainly produced in the enteroendocrine L cells located in the distal intestine. Their effect is mediated through their binding with specific receptors, though part of their biological action may also involve neural modulation. GIP and GLP-1 are both rapidly degraded into inactive metabolites by the enzyme dipeptidyl-peptidase-IV (DPP-IV). In addition to its effects on insulin secretion, GLP-1 exerts other significant actions, including stimulation of insulin biosynthesis, inhibition of glucagon secretion, inhibition of gastric emptying and acid secretion, reduction of food intake, and trophic effects on the pancreas. As the insulinotropic action of GLP-1 is preserved in type 2 diabetic patients, this peptide was a candidate as a therapeutic agent for this disease. A number of pharmacological strategies have been developed to provide continuous delivery of GLP-1 and to prevent degradation of GLP-1, including continuous administration of GLP-1, DPP-IV inhibitors and DPP-IV resistant GLP-1 analogues. Recent results of the most clinically advanced incretin mimetics confirmed their efficacy to improve glycemic control in type 2 diabetic patients. Further results are expected to confirm the efficacy/safety profile of these compounds, and to find their place in the therapeutic strategy of type 2 diabetes.

Objectif La dyslipidemie est un facteur de risque important des complications macroangiopathiques chez les patients diabetiques. La reduction du LDL-cholesterol (LDLc) permet de diminuer la morbimortalite cardiovasculaire. Les recommandations de la Societe Europeenne de Cardiologie (ESC) concernant les objectifs de concentrations de LDLc ont ete mises a jour en 2011. Notre objectif est d'evaluer la proportion des patients atteignant les objectifs de LDLc en fonction des recommandations europeennes notamment en prevention secondaire et en cas de nephropathie diabetique (objectifs de LDLc Patients et Methodes Nous avons collecte les donnees des patients diabetiques ( n =5 760) ayant consulte au Centre Universitaire du Diabete et de ses Complications de l'hopital Lariboisiere entre septembre 2014 et aout 2015. Nous avons analyse les resultats de 3 539 patients pour lesquels le LDLc etait disponible et calculable (triglyceridemie Resultats Notre cohorte inclut des diabetiques a haut risque cardiovasculaire (les donnees sont exprimees en mediane (Q1-Q3)) : homme 57,8 % ; âge 58 ans (18-80) ; IMC 27,5kg/m 2 (16,42-50,22) ; obeses 33 % ; duree de diabete 13 ans (0-59) ; HbA 1c 7,4 % (4,6-14) ; hypertension 68 % ; tabac 16,3 % ; nephropathie 39,6 % ; prevention cardiovasculaire secondaire 39 %. Chez les patients avec nephropathie, le LDLc est de 0,89g/L (0,25-2,13) vs 1,01g/L (0,35-2,06) chez ceux sans nephropathie ( p Conclusions Dans notre cohorte de patients diabetiques, le LDLc atteint rarement les objectifs de l'ESC. Une insuffisance de prescription peut expliquer ces resultats en prevention primaire alors qu'en prevention secondaire le probleme de l'efficacite et/ou de la dose choisie peut se poser.