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Objective: Foot ulcers are a common complication of diabetes and are associated with an increase in lower limb amputation and death. Early referral to a specialised unit is recommended. The aim of this study was to assess the characteristics of new-patient referrals to specialised diabetes foot care units across Europe and to determine the factors involved in delayed referral. Method: In this prospective observational study, consecutive patients with a new foot ulcer presenting to nine diabetic foot centres in five European countries (France, Germany, Italy, Spain and the UK) were included. Results: Some 25% of the 332 patients included had presented with a foot ulcer >3 months before referral to the participating foot clinic. Compared with patients referred earlier, patients with a long time to referral (>3 months) were older (p=0.006) and had a less severe wound according to Infectious Diseases Society of America (IDSA) classification (p=0.003) and University of Texas classification (grade D=infection + peripheral artery disease, p=0.004). Conclusion: The proportion of patients with a diabetic foot ulcer (DFU) referred to a specialised unit >3 months after the beginning of the ulcer remained high throughout Europe. Patients with severe DFU were, however, referred more quickly by front line health professionals. Primary care professionals need to be made aware of the importance of early referral to a specialised unit in order to improve the management of foot disease in patients with diabetes. Declaration of interest: The authors have no conflicts of interest to declare.

Resume Une patiente de 56 ans, diabetique de type 2, presentait des episodes d’hypoglycemies, qui ont persiste apres arret du traitement antidiabetique. Une epreuve de jeune authentifie une hypoglycemie organique, a 0,34 g/L, insulinemie a 6 mUI/L, peptide C a 1,9 ng/mL (normes : 0,5–3,0 ng/mL) et proinsuline a 3,72, puis 4,5 pmol/L (normes : 1,28–3,84 pmol/L). Aucune lesion n’est retrouvee au scanner ou a l’echo-endoscopie. La scintigraphie a la somatostatine est negative. Ces elements font ainsi porter le diagnostic de nesidioblastose. Des traitements par diazoxide et octreotide sont successivement mis en place, sans succes. Sous pasireotide LAR, les hypoglycemies disparaissent, avec meme une elevation franche des glycemies, des hyperglycemies bien controlees sous sitagliptine. La patiente est depuis 2 ans sous pasireotide LAR, sans recidive des hypoglycemies a ce jour.

The COVID-19 pandemic has had a detrimental impact on mental health, including on food-related behaviors. However, little is known about the effect of the pandemic on anorexia nervosa (AN). We sought to assess an association between the COVID-19 pandemic and a potential increase in hospitalizations for AN in France. We compared the number of hospitalizations with a diagnosis of AN during the 21-month period following the onset of the pandemic with the 21-month period before the pandemic using Poisson regression models. We identified a significant increase in hospitalizations for girls aged 10 to 19 years (+45.9%, RR = 1.46[1.43–1.49]; p < 0.0001), and for young women aged 20 to 29 (+7.0%; RR = 1.07[1.04–1.11]; p < 0.0001). Regarding markers of severity, there was an increase in hospitalizations for AN associated with a self-harm diagnosis between the two periods. Multivariate analysis revealed that the risk of being admitted for self-harm with AN increased significantly during the pandemic period among patients aged 20–29 years (aOR = 1.39[1.06–1.81]; p < 0.05 vs. aOR = 1.15[0.87–1.53]; NS), whereas it remained high in patients aged 10 to 19 years (aOR = 2.40[1.89–3.05]; p < 0.0001 vs. aOR = 3.12[2.48–3.98]; p < 0.0001). Furthermore, our results suggest that the pandemic may have had a particular effect on the mental health of young women with AN, with both a sharp increase in hospitalizations and a high risk of self-harming behaviors.

Mean amplitude of glucose excursion (MAGE) is considered as the “gold standard” for assessing the short-term within-day glycemic variability (GV), which is an important component of overall glycemic control. A 14-day continuous glucose monitoring system is now widely used and allows easier assessment of GV. However, it is still unknown whether MAGE, usually calculated on a 48-hour period is identical whatever the time during the 14-day lifespan of the sensor and whether a longer time period might give additional information. We evaluated in 68 patients with type 1 diabetes, MAGE during three 2-day periods (day1-day3; day6-day8; day11-day13) and during periods of 3 days and 4 days. MAGE calculated at the three 2-day periods were identical and not different from MAGE of the 3-day or 4-day periods.

Introduction Inappropriate insulin secretion could be due to several diseases. Nesidioblastosis is characterized by diffuse hyperplasia of pancreatic beta cells, causing organic hypoglycemia. No pancreatic lesions are found on the imaging of patients with this condition. Diazoxide is used as a first-line treatment but can be poorly tolerated because of its side effects, and therapeutic failure is possible. Somatostatin analogues have limited efficacy because of their poor affinity to somatostatin (SST) receptors. Pasireotide is a somatostatin analogue with a much higher affinity to SST receptors, especially SST5, and it could thus be more efficient for treating nesidioblastosis-related hypoglycemia. Observation A 56 years-old diabetic woman had symptoms of hypoglycemia, persistent after treatment's withdrawal. A fasting test authentify an organic hypoglycemia, at 34mg/dL, a plasma insulin level at 6mUI/L above the 5 mU/L threshold, a C-peptide level at 1.9 ng/mL above the threshold of 0.6, and an insulin/C-peptide ratio 0.066, below the threshold of 1. No lesions were found on CT-scan or endoscopic ultrasound. Somatostatin receptor scintigraphy was also negative. Diazoxide and octreotide failed to improve the recurrence of hypoglycemia episodes. With pasireotide LAR, hypoglycemia disappeared and glycemia increased. Hyperglycemia was controlled with sitagliptin. The patient has now been treated with pasireotide LAR for two years, with no more episode of hypoglycemia until now. Discussion We present the first case of nesidioblastosis treatment with pasireotide LAR, with success. Patients diagnosed with nesidioblastosis and diazoxide-resistant hypoglycemia, or who experience difficulties with other treatments, could use pasireotide LAR in conjunction with glycemia monitoring, particularly if they are diabetic.

Obesity is increasing in patients with type 2 diabetes. A possible reduced association between fructosamine and glycated hemoglobin (HbA1c) in obese individuals has been previously discussed, but this has never been specifically evaluated in type 2 diabetes, and the potential influence of body fat mass and fat distribution has never been studied. We studied 112 type 2 diabetes patients with assessment of fat mass, liver fat and fat distribution. Patients with body mass index (BMI) above the median (34.9 kg/m2), versus BMI below the median, had a correlation coefficient between fructosamine and HbA1c significantly reduced (r = 0.358 vs r = 0.765). In the whole population, fructosamine was correlated negatively with BMI and fat mass. In multivariate analysis, fructosamine was associated with HbA1c (positively) and fat mass (negatively), but not with BMI, liver fat or fat distribution. The association between fructosamine and HbA1c is significantly reduced in the most obese type 2 diabetes patients, and this is mostly driven by increased fat mass., The association between fructosamine and glycated hemoglobin is significantly reduced in the most obese type 2 diabetes patients, and this is mostly driven by increased fat mass.

Background Diabetes management has not been evaluated in French nursing homes (NHs) for 10 years. Objectives The present study aimed to compare the management of diabetes with guidelines in older patients living in NHs. Design Observational, retrospective and multicentre study carried out in 13 NH in the Cote d’Or region of France. Settings and subjects Between January and June 2018, all NH residents older than 65 years and known to have diabetes (n = 148) were included. Methods Epidemiological, clinical and biological data and diabetes characteristics were collected from the medical records. Results The average glycated haemoglobin (HbA1C) was 7.2 ± 1.2%. In total, 51% of patients had HbA1C Conclusions We found that glycaemic control was too tight in at least 36.5% of the total population and that 40% of patients with HbA1C

Objective The Type A personality, characterized by impatience, strong career ambition and competitiveness, is associated with greater sensitivity to external stress. Type 1 diabetes (T1D) is an auto-immune disease, which is potentially influenced by stress, unlike type 2 diabetes (T2D). The aim of this study was to assess whether individuals with T1D and T2D exhibited significant differences on the Type A personality scale. We also assessed personality in patients with thyroid auto-immune diseases to validate potential links between auto-immune disease and Type A personality. Design and methods The Bortner questionnaire was used to assess Type A personality in 188 patients with T1D, 430 patients with T2D and 85 patients with auto-immune thyroid disease (Graves’ disease or Hashimoto’s thyroiditis). Results Type A Bortner scores were significantly higher in T1D patients than in T2D patients (188 ± 34 vs 177 ± 36, P P = 0.860). Conclusion Patients with auto-immune T1D have higher Type A scores than T2D patients. Furthermore, patients with auto-immune thyroid disease also have elevated Type A scores similar to those observed in type 1 diabetes, suggesting that an elevated Type A score in T1D is potentially related to its auto-immune origin. This suggests a possible link between Type A personality and auto-immune diseases via stress-triggering psychobiological pathways. The different personality score between T1D and T2D is an important factor, which could influence self-care coping strategies in diabetes and long-term prognosis.

International audience; Background: The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. Method: This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5 years. Results: Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P

Dysregulation of the renin angiotensin system (RAS) has been proven in diabetic animal models, and studies in humans show that diuretic use is associated with lower limb amputation in diabetes. While patients with diabetes are often treated with diuretics and RAS blockers, the association between wound healing and these treatments is still unknown. We aimed to determine whether the use of diuretics and RAS blockers could influence healing of diabetic foot ulcers (DFU).Two hundred seventy-six patients referred to a specialized diabetes foot care unit for a new foot ulcer were included in this retrospective observational study.Healing rate was significantly higher in patients not treated with diuretics than in those receiving diuretics (75.9 vs. 62.9%, P = 0.026) and in patients treated with angiotensin receptor blockers (ARB) than in those not treated with ARB (79.5 vs 64.4%, P = 0.012). The difference was not significant for angiotensin conversion enzyme inhibitor use. ARB use was independently and positively associated with wound healing in a multivariate adjusted model including several factors affecting wound healing (odds ratio (OR) 2.79 [1.13, 6.86] P = 0.025). Diuretic use was negatively associated with wound healing in univariate analysis (OR 0.54 [0.32, 0.91] P = 0.02) but not in multivariate adjusted analysis (OR 0.53 [0.26, 1.10] P = 0.088).This novel study found that ARB use is independently and positively associated with wound healing in 276 patients with DFU. On the contrary, diuretics were associated with healing rate only at univariate analysis. Further prospective studies are needed to confirm our findings.

Diabetes is associated with an accelerated development of atherosclerosis. Specific mechanisms related to diabetes and hyperglycemia may play a role in this process. In particular, alterations of arachidonic acid (AA) metabolism have been reported. Our main goal was to investigate for differences in the concentration of LTB4 and RvD1 as well as selected cyclooxygenase-derived mediators in carotid plaques from diabetic and non-diabetic patients. We also aimed to analyze the relationship between omega 6 and omega 3 Poly-Unsaturated Fatty acids (PUFAs) content in the plaques and the concentrations of these lipid mediators.29 type 2 diabetic patients and 30 control patients admitted for surgical treatment of carotid stenosis were enrolled in the present study. Carotid plaques were harvested for in-depth lipidomic profiling.No differences for LTB4 or other lipid mediators were observed between diabetic and non-diabetic patients. RvD1 levels were below the threshold of quantification in most of the samples. A significant correlation was found between LTB4 and 5(S)-HETE levels. Omega 3 enrichment was not significantly different between control and diabetic plaques. There was a negative correlation between DHA/AA ratio and the level of 5(S)-HETE while there was a positive association with TXB2 and PGD2 concentrations.Our results does not support the hypothesis of a specific involvement of LTB4 or COX-derived mediators in diabetic atherosclerosis. The relationship between DHA enrichment and the concentrations of specific inflammatory mediators within the plaque is of interest and will need to be confirmed in larger studies.

International audience; Type 2 diabetes mellitus (T2DM) is a frequent comorbidity in patients with cirrhosis that is projected to rise in prevalence due to the worldwide burden of obesity, insulin-resistance and non-alcoholic fatty liver disease. The management of T2DM in patients with cirrhosis is complex given the requirement for accurate adaptation according to the level of liver function impairment, with lack of summary of the little evidence available in the literature. Here, we summarise the data available with respect to the epidemiology and the impact of T2DM in patients with cirrhosis, as well as those on the management of T2DM in these patients. We provide guidance for the diagnosis of T2DM and the monitoring of glycaemic control in patients with cirrhosis, and for the management of nutrition and pharmacological treatments in relation to the level of liver dysfunction.

The impact of cholesteryl ester transfer protein (CETP) on atherosclerotic development in humans remains unclear. Plasma cholesteryl ester transfer was shown to be associated with carotid intima-media thickness in type 2 diabetic (T2D) patients with adequate metabolic control. Since glycation of CETP may influence cholesteryl ester transfer processes, it is important to determine if plasma cholesteryl ester transfer is still a determinant of carotid intima-media thickness (IMT) in patients with poorly controlled diabetes. The aim of the present study was to determine whether CETP activity influences carotid IMT in T2D patients with poor metabolic control. In 110 individuals with T2D, we measured CETP mass concentration with ELISA, CETP activity with a radioactivity method and carotid intima-media thickness with high-resolution real-time B-mode ultrasonography. The mean HbA1C was 8.8 ± 1.7%. Carotid IMT did not correlate with CETP activity in the total population. In T2D patients with HbA1C

AIMS/HYPOTHESIS: The aim of this study was to examine the impact of the COVID-19 epidemic on the hospitalization rates for diabetic foot ulcer (DFU), osteomyelitis and lower limb revascularization procedure in people with DFU. METHODS: This nationwide retrospective cohort study included hospital data on all people hospitalized in France for diabetes in weeks 2-43 in 2020, including the COVID-19 lockdown period, compared to same period in 2019. RESULTS: The number of hospitalizations for DFU decreased significantly in weeks 12-19 (during the lockdown) (p

BackgroundLittle is known about the prevalence of hypoglycaemia in older people with diabetes. However, the HbA1c goal is ≥8% for institutionalised patients with treatments that can cause hypoglycaemia.PurposeWe aimed to assess the prevalence of hypoglycaemia with continuous glucose monitoring and to evaluate the link with HbA1C in older institutionalised patients with diabetes taking potentially hypoglycaemia-inducing drugs.DesignProspective, multicentre study carried out in six geriatric care centres in the Côte d’Or region of France between January 2019 and July 2020.Settings, subjects and methodsA FreeStyle Libre Pro® (FSLP) was worn for up to 14 days in blinded mode in 42 patients taking at least one potentially hypoglycaemia-inducing antidiabetic drug.ResultsTwo hundred and forty-two hypoglycaemic events were detected in 79% (n = 33) of patients wearing the FSLP. One or more hypoglycaemic event was detected in 100% of patients with HbA1C ConclusionsWe report a very high prevalence of hypoglycaemia, with a significant proportion of severe hypoglycaemia, in older institutionalised patients with diabetes taking potentially hypoglycaemia-inducing drugs. Having HbA1C

OBJECTIVE Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect of the GLP-1 agonist liraglutide on the metabolism of apoB100-containing lipoproteins. RESEARCH DESIGN AND METHODS We performed an in vivo kinetic study with stable isotopes (L-[1-13C]leucine) in 10 patients with T2D before and after 6 months of treatment with liraglutide (1.2 mg/day). We also evaluated in mice the effect of liraglutide on the expression of genes involved in apoB100-containing lipoprotein clearance. RESULTS In patients with T2D, liraglutide treatment significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 ± 0.11 g/L, P = 0.011) and fasting triglycerides (1.76 ± 0.37 vs. 2.48 ± 0.69 mmol/L, P = 0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL1-apoB100 (4.11 ± 1.91 vs. 2.96 ± 1.61 pools/day, P = 0.005), VLDL2-apoB100 (5.17 ± 2.53 vs. 2.84 ± 1.65 pools/day, P = 0.008), and IDL-apoB100 (5.27 ± 2.77 vs. 3.74 ± 1.85 pools/day, P = 0.017) and in catabolism of LDL-apoB100 (0.72 ± 0.22 vs. 0.56 ± 0.22 pools/day, P = 0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced proprotein convertase subtilisin/kexin type 9 (PCSK9), retinol-binding protein 4 (RBP4), and tumor necrosis factor-α (TNF-α) gene expression in adipose tissue and decreased PCSK9 mRNA and increased LDL receptor protein expression in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver. CONCLUSIONS Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL1, VLDL2, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100-containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2D.

The aim of this large retrospective cohort study was to use a quasi-exhaustive national medico-administrative database of deliveries in France to determine the risk of developing pancreatic cancer (PC) in women with a history of gestational diabetes mellitus (GDM). This nationwide population-based study included women aged 14&ndash, 55 who gave birth between 1st January 2008 and 31 December 2009. The women were followed-up epidemiologically for eight years. Survival analyses using Cox regression models, adjusted for age, subsequent type 2 diabetes, and tobacco consumption, were performed on the time to occurrence of hospitalization for PC. The onset of GDM, tobacco consumption and subsequent type 2 diabetes were considered as time-dependent variables. Among 1,352,560 women included, 95,314 had a history of GDM (7.05%) and 126 women were hospitalized for PC (0.01%). Over the eight years of follow-up, GDM was significantly associated with a higher risk of hospitalization with PC in the first Cox regression model adjusted for age and subsequent type 2 diabetes (HR = 1.81 95% CI [1.06&ndash, 3.10]). The second Cox regression model adjusted for the same covariates, plus tobacco consumption, showed that GDM was still significantly associated with a higher risk of hospitalization for PC with nearly the same estimated risk (HR = 1.77 95% CI [1.03&ndash, 3.03]). Gestational diabetes was significantly associated with a greater risk of hospital admission for pancreatic cancer within eight years, regardless of subsequent type 2 diabetes.

Aim Type A personality—characterized by time urgency, strong drive, and a need for achievement and competitiveness—has been shown to be associated with reduced mortality in patients with diabetes. However, it is not known whether a Type A personality might protect against diabetic foot ulcer (DFU). This prompted our present analysis of the association between Type A personality and DFU. Methods The Bortner Scale questionnaire was used to assess Type A personality in 386 patients with type 2 diabetes (T2D), including 104 patients also presenting with, and 282 presenting without, DFU. Additional questionnaires were used to assess perceived stress and depression. Results Type A Bortner scores were significantly lower in T2D patients with vs without DFU (166.64 ± 38.76 vs 178.79 ± 36.61, respectively; P = 0.005). In patients with DFU, the prevalence of Type A personality traits was significantly lower than in those without DFU (48% vs 64.5%, respectively; P = 0.005) whereas, in contrast, Type B personality traits (the opposite of Type A) were more prevalent (52% vs 35.5%, respectively; P = 0.005). On multivariate analysis, Type A Bortner scores were negatively associated with DFU (P = 0.008) independently of age, gender, BMI, depression scores or perceived stress. Conclusion The Type A personality, characterized by competitiveness and a need for achievement, is significantly less frequently seen in T2D patients with DFU. On the other hand, the Type B personality is much more prevalent in such patients. It may be that the Type B personality, which is characterized by fewer problem-focused coping strategies and a decreased adherence to care, might favour the development of DFU.

International audience; For many years, scientists have been looking for specific biomarkers associated with cancer cells for diagnosis purposes. these biomarkers mainly consist of proteins located at the cell surface (e.g. the TrkB receptor) whose activation is associated with specific metabolic modifications. Identification of these metabolic changes usually requires cell fixation and specific dye staining. MCARS microspectroscopy is a label-free, non-toxic, and minimally invasive method allowing to perform analyses of live cells and tissues. We used this method to follow the formation of lipid droplets in three colorectal cancer cell lines expressing TrkB. MCARS images of cells generated from signal integration of cH 2 stretching modes allow to discriminate between lipid accumulation in the endoplasmic reticulum and the formation of cytoplasmic lipid droplets. We found that the number of the latter was related to the TrkB expression level. This result was confirmed thanks to the creation of a HEK cell line which over-expresses TrkB. We demonstrated that BDNF-induced TrkB activation leads to the formation of cytoplasmic lipid droplets, which can be abolished by K252a, an inhibitor of TrkB. So, MCARS microspectroscopy proved useful in characterizing cancer cells displaying an aberrant lipid metabolism. Cancer is characterized by an uncontrolled cell growth, and tumor cell dissemination enabling the spread of cancer from its site of origin 1. For a number of years, studies have focused on the identification of specific biomarkers associated with cancer processes. Biomarkers comprise many molecular structures such as DNA, mRNA, proteins or metabolites. However, in most cases, cancer biomarkers consist of proteins such as receptors at the cell surface 1,2. Human epidermal growth factor receptor (ErbB) family has been the first receptor family discovered as involved in human cancers. In this family, the most common receptors are EGFR (Epithelial Growth Factor Receptor) and HER2 (Human Epidermal Growth Factor Receptor 2) 3. Other biomarkers have also been discovered which are specific for certain types of cancer. For example, breast cancer can be detected by the presence of biomarkers such as HER2 or BRCA1, while KRAS and TP53 biomarkers are linked to non-small cell lung cancer 4. Aside from distinguishing cancer cells from healthy ones, these biomarkers also allow to determine the stage of the cancer. Neurotrophins have been discovered in the central and peripheral nervous systems, thereby regulating the growth and differentiation of neurons 5. The neurotrophin family is composed of three major receptors, Trk A, B and C, associated with specific ligands: NGF binds to TrkA, BDNF and NT-4 bind to TrkB and NT-3 binds to TrkC 6. When they are expressed in other human tissues, neurotrophins are associated with tumorigenesis, metastases, for example in ovarian, breast, and colorectal cancers 7. The BDNF/TrkB complex is mainly correlated with colorectal cancer (CRC) and is of poor prognosis 8. BDNF binding to TrkB induces an autophosphorylation open 1 PEIRENE, EA 7500

Dyslipidaemia in type 2 diabetes mellitus (T2DM), which increases cardiovascular risk, includes abnormal metabolism of low-density lipoproteins (LDL). Our group has recently shown that liraglutide increases LDL catabolism in patients with T2DM and that it reduces the expression of PCSK9 (a major inhibitor of LDL-receptor expression) in vitro and in mice. This prompted us to study the effect of liraglutide on plasma PCSK9 level in patients with T2DM.We studied prospectively 82 patients with T2DM (51 without statins, 31 with statins). Plasma PCSK9 and plasma lipids were measured before and six months after the initiation of a treatment with liraglutide at a dose of 1.2 mg/day.Plasma PCSK9 was significantly reduced by liraglutide treatment (214.9 ± 56.4 vs 244.5 ± 99.2 ng/ml, P = 0.024) in patients not on statins, but not in patients treated with statins (301.1 ± 91.5 vs 281.2 ± 96.9 ng/ml, P = 0.41). In patients not on statins, a very significant 17% decrease in plasma PCSK9 was observed in patients with baseline haemoglobin A1c (HbA1c)10% (n = 33; mean = -45.0 ng/ml, P = 0.013), when it was not observed in patients with baseline HbA1c ≥ 10% (n = 18; mean = +5.2 ng/ml, P = 0.75). In multivariate analysis, baseline HbA1c was an independent factor associated with plasma PCSK9 reduction, in patients not on statins.Treatment with liraglutide induces a significant reduction of plasma PCSK9 in patients with T2DM not on statins. This is in line with the acceleration of LDL catabolism that has been observed with liraglutide. However, this decrease in plasma PCSK9 is significantly influenced by glycaemic control and is not observed in patients with poorly controlled T2DM.

Aim The aim of the present study was to identify the affected gene in a French family with maturity-onset diabetes of the young (MODY) using whole-exome sequencing (WES). Methods WES was performed in one patient with MODY, and candidate variants were confirmed in members of the immediate family by Sanger sequencing. Results In the proband, a new heterozygous missense mutation (c.340A>C) was identified in the NEUROD1 gene by WES analysis and confirmed by Sanger sequencing. Additional Sanger sequencing of the proband's sister and mother revealed the same heterozygous mutation. The proband and his sister displayed typical clinical characteristics of MODY, while their mother had the same typical MODY features except for later onset. When clinical and biological profiles were established for all three patients, the severity of diabetes-related complications varied substantially from one family member to another. Conclusion A novel missense mutation found in NEUROD1 was associated with MODY 6 features in a single French family.

Thyroiditis is a frequent and mostly benign disease that can sometimes disrupt the thyroid balance. Their diagnosis, as well as their aetiology, is a necessary step in the management of the patients. Painful thyroiditis includes acute thyroiditis of infectious origin and subacute thyroiditis. The first one can be treated by antibiotics or antifungals depending on the germ found. The second one will be treated with non-steroidal anti-inflammatory drugs or corticosteroids. In cases of Hashimoto's thyroiditis with overt hypothyroidism, replacement therapy with L-thyroxine will be adapted to the TSH level. As amiodarone treatment provides dysthyroidism, the thyroid status should be monitored regularly. Hypothyroidism will be treated using thyroid replacement therapy. Hyperthyroidism imposes a stop of amiodarone when it is possible. Treatment with synthetic antithyroid drugs (propyl-thio-uracil) or corticosteroids could be used whether there is an underlying thyroid disease or not. Immunotherapies with anti-PD-1/PDL1 or anti-CTLA-4 can also provide dysthyroidism. A monitoring of the thyroid assessment needs to be done in these patients, even if there are no clinical signs, which are not very specific in this context. The treatment of hypothyroidism will be based on thyroid replacement therapy according to the TSH level and the presence or absence of anti-TPO antibodies. Treatment of symptomatic hyperthyroidism may involve a prescription of beta-blockers, or synthetic antithyroid drugs in case of positive anti-TSH receptor antibodies. In all cases, it is desirable to contact an endocrinologist to confirm the diagnosis hypothesis and to decide on a suitable treatment.

The aim of this study was to examine the associations between hospitalisation for diabetic ketoacidosis and subsequent hospitalisation for suicide attempt in young adults with type 1 diabetes. This nationwide historical cohort study included hospital data on all young people hospitalised in France for type 1 diabetes in 2008. Epidemiological follow-up focused on hospitalisations (medical and psychiatric hospital data) from the index hospitalisation to 2017. Survival analyses were done using a Cox proportional hazards regression model to explore the association between hospitalisation for ketoacidosis and subsequent hospitalisation for a suicide attempt. In 2008, 16,431 people aged 18–35 years had a hospitalisation mentioning type 1 diabetes. Among them, 1539 (9.4%) had at least one hospitalisation for ketoacidosis between 2008 and 2010. At 9 years, 7.2% of the group hospitalised for ketoacidosis had been hospitalised for a suicide attempt vs only 2.5% in the group not hospitalised for ketoacidosis. The association between hospitalisation for ketoacidosis and suicide attempt decreased over time and was no longer significant after 5 years. We found that young adults admitted to hospital for diabetic ketoacidosis have an increased risk of being admitted to hospital for a subsequent suicide attempt. The risk of a suicide attempt was the highest in the 12 months following the ketoacidosis episode. Our findings support the recommendation that screening for depression and suicide risk should be part of the routine clinical assessment of individuals with type 1 diabetes and ketoacidosis.

Myogenesis is a physiological process which involves the proliferation of myoblasts and their differentiation into multinucleated myotubes, which constitute the future muscle fibers. Commitment of myoblasts to differentiation is regulated by the balance between the myogenic factors Pax7 and MyoD. The formation of myotubes requires the presence of glycans, especially N‐glycans, on the cell surface. We examined here the involvement of α2,6 sialylation during murine myoblastic C2C12 cell differentiation by generating a st6gal1‐knockdown C2C12 cell line; these cells exhibit reduced proliferative potential and precocious differentiation due to the low expression of Pax7. The earlier fusion of st6gal1‐knockdown cells leads to a high fusion index and a drop in reserve cells (Pax7+/MyoD−). In st6gal1‐knockdown cells, the Notch pathway is inactivated; consequently, Pax7 expression is virtually abolished, leading to impairment of the proliferation rate. All these results indicate that the decrease in α2,6 sialylation of N‐glycans favors the differentiation of most cells and provokes a significant loss of reserve cells., The knockdown of st6gal1 in C2C12 murine myoblastic cells induces an increase in cell fusion and in myotube formation at the expense of cell proliferation and maintenance of a reserve cell pool. The decrease in α2,6 sialylated N‐glycans may affect the receptors that would be involved in the Notch signaling pathway that results in reduced expression level of Pax7.

Resume Le diabete est frequemment associe a des maladies chroniques du foie et, notamment, l’infection par le virus de l’hepatite C, la cirrhose, et la steatose metabolique. La particularite des pathologies hepatiques au cours du diabete doit inciter les cliniciens a adapter leurs objectifs de traitements et de surveillance aux differentes situations cliniques. Ces differentes pathologies hepatiques peuvent impliquer une prise en charge differente sur le plan nutritionnel, sur la surveillance de l’equilibre glycemique, et sur l’utilisation des therapeutiques antidiabetiques.

IF 3.340; International audience; AIMS:Women who had gestational diabetes mellitus (GDM) have a high risk of type 2 diabetes mellitus (T2DM) in the years following pregnancy. Most follow-up screening studies have been conducted in limited geographical areas leading to large variability in the results. The aim of our investigation was to measure how the publication of guidelines affected early screening for T2DM after a pregnancy with GDM during the period 2007-2013, in France.METHODS:We conducted a retrospective cohort study in a representative sample of 1/97th of the French population using data from the "National Health Insurance Inter-Regime Information System," which collects individual hospital and non-hospital data for healthcare consumption.RESULTS:The sample included 49,080 women who gave birth in 2007-2013. In the following 3 months, only 18.49% of women with GDM had an oral glucose tolerance test or a blood glucose test in 2007. This rate had not significantly increased in 2013 (p = 0.18). The proportion of women with GDM who had the recommended glycemic follow-up at 3 months (20.30 vs. 21.58%, p = 0.19) and 6 months (32.48 vs. 37.16%, p = 0.08) was not significantly different before the guidelines (2008-2009) and after the guidelines (2012-2013). At 12 months, the difference was significant (46.77 vs. 54.05%, p = 0.009).CONCLUSION:Postpartum screening has improved only slightly since the guidelines and remains largely insufficient, with less than 25% of women with GDM screened in the first 3 months. In the first year after delivery, less than 60% of women were screened for T2DM.

Introduction Les inhibiteurs de mTOR (mTORi), traitements anticancereux, sont responsables d’effets secondaires metaboliques. Ils n’ont jamais ete evalues en situation de vie reelle. Cette etude a pour objectif de determiner le devenir de patients presentant une dyslipidemie ou un diabete sous mTORi, mais aussi l’incidence et la prise en charge des anomalies metaboliques apparues sous mTORi en l’absence d’antecedent metabolique connu. Methode Etude retrospective et monocentrique chez les 177 patients places sous everolimus, au centre anti-cancereux de Dijon, entre mai 2015 et novembre 2018. Resultats Le diabete a ete depiste chez tous les patients. Son incidence etait de 9 % et son delai moyen d’apparition de 160 ± 173 jours. Un traitement antidiabetique pharmacologique a ete introduit chez 41 % des patients diagnostiques. La disparition du diabete a l’arret des mTORi a concerne 40 % des patients diagnostiques, qui avaient tous beneficie uniquement de regles hygieno-dietetiques. Une dyslipidemie a ete decouverte chez 14 % des patients, mais n’a ete depiste que chez 42 % des patients. Conclusion Notre etude est la premiere a s’interesser aux complications metaboliques des mTORi en situation de vie reelle. L’incidence du diabete est importante et le desequilibre glycemique est variable. La normalisation de l’homeostasie glucidique a l’arret des mTORi est possible, mais reste imprevisible. Le depistage de la dyslipidemie est insuffisant ce qui rend les donnees sur ce point difficiles a interpreter. Il apparait important d’ameliorer la mise en application des recommandations en vigueur pour optimiser la prise en charge metabolique des patients traites par mTORi.