Metabolically 'extremely unhealthy' obese and non-obese patients with diabetes and the risk of cardiovascular events: a French nationwide cohort study.

BACKGROUND: Non-obese patients with diabetes mellitus (DM) are becoming more prevalent, but their cardiovascular risk (CV) especially when accompanied with cardio-renal-metabolic co-morbidities (hypertension, chronic kidney disease, hyperlipidemia) is not well characterised. The aim of the study was to assess the CV risk among patients with DM in relation to obesity and cardio-renal-metabolic co-morbidities. MATERIALS AND METHODS: This was a cohort study of all patients with DM without a history of major adverse cardiovascular event who were hospitalized for any reason in France in 2013 with at least 5 years of follow-up. They were categorized by the presence of obesity vs no obesity, as well as three cardio-renal-metabolic co-morbidities: hypertension, chronic kidney disease, hyperlipidemia. 'Extremely unhealthy' patients with DM were defined as those having all 3 co-morbidities. RESULTS: There were 196,112 patients (mean age 65.7 (SD 13.7) years; 54.3% males) included into the analysis. During a mean follow-up of 4.69 ± 1.79 years, when adjusted for multiple covariates, the non-obese and 'extremely unhealthy' obese patients had the highest risk of CV death [aHR 1.40 (95% CI, 1.22-1.61) and 1.48 (95% CI, 1.25-1.75), respectively]. The 'extremely unhealthy' obese had the highest risk of MACE-HF [aHR 1.84 (95% CI, 1.72-1.97)] and new-onset AF [aHR 1.64 (95% CI, 1.47-1.83)]. CONCLUSION: Both non-obese and obese patients with DM with associated cardio-renal-metabolic co-morbidities are an 'extremely unhealthy' phenotype with the highest risk of CV death and CV events.

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties.

Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin. EVs also constitute stable conveyors of adiponectin in the blood circulation. Adiponectin-enriched sEVs display in vitro insulin-sensitizing effects by binding to regular adiponectin receptors. Adoptive transfer of adiponectin-enriched sEVs in high-fat-diet-fed mice prevents animals from gaining weight and ameliorated insulin resistance and tissue inflammation, with major effects observed in the AT and liver. Our results therefore provide information regarding adiponectin-related metabolic responses by highlighting EVs as delivery platforms of metabolically active forms of adiponectin molecules.

3-Month Post-Operative Increase in FGF21 is Predictive of One-Year Weight Loss After Bariatric Surgery.

PURPOSE: The association between bariatric surgery outcome and blood levels of fibroblast growth factor 21 (FGF21) remains controversial. Many patients displayed stable or decreased FGF21 one year after bariatric surgery. Nevertheless, there is often an early increase FGF21 concentration in the post-surgery period. The aim of this study was to investigate the relationship between 3-month FGF21 response and percentage total weight loss at one year after bariatric surgery. MATERIALS AND METHODS: In this prospective monocentric study, a total of 144 patients with obesity grade 2-3 were included; 61% of them underwent a sleeve gastrectomy and 39% a Roux-en-Y gastric bypass. Data analysis was carried out to determine the relation between 3-month plasma FGF21 response and weight loss one year after bariatric surgery. Multiple adjustments were done including degree of weight loss after 3 months. RESULTS: FGF21 significantly increased between baseline and Month 3 (n = 144, p < 10-3), then decreased between Month 3 and Month 6 (n = 142, p = 0.047) and was not different from baseline at Month 12 (n = 142, p = 0.86). The 3-month-FGF21 response adjusted to body weight loss was not different between types of bariatric surgery. The 3-month-FGF21 response was associated to body weight loss at Month 6 (r = -0.19, p = 0.02) and Month 12 (r = -0.34, p < 10-4). After multiple regression analysis, only Month 12 body weight loss remained associated to 3-month FGF21 response (r = -0.3, p = 0.02). CONCLUSION: This study showed that the magnitude of changes in FGF21 at 3 months after bariatric surgery emerged as an independent predictor of one-year body weight loss irrespective of the type of surgery.

Type 2 diabetes and cardiorenal syndromes. A nationwide French hospital cohort study.

AIM: Type 2 diabetes mellitus (T2DM) is a risk factor for cardiac and renal complications; its effect on cardiorenal syndromes is unknown. METHODS: In a French nationwide cohort of 5,123,193 patients hospitalized in 2012 with ≥5 years of follow-up, we assessed the effect of T2DM on cardiorenal syndrome (CRS) (using cardiorenal, renocardiac, and simultaneous subtypes) incidence and outcomes using 1:1 propensity matching. RESULTS: Among 4,605,236 adults without cardiorenal syndrome, 380,581 (8.5%) with T2DM were matched to 380,581 adults without T2DM. During follow-up, CRS occurred in 104,788 patients: simultaneous n = 25,225 (24.0%); cardiorenal n = 51,745 (49.4%); renocardiac n = 27,818 (26.5%). T2DM doubled the risk of incident CRS (1.30% versus 0.65%/year; adjusted hazard ratio (HR) for any cardiorenal syndrome: 2.14 [95% confidence interval 2.10;2.19]; renocardiac: 2.43 [2.34;2.53]; cardiorenal: 2.09 [2.03;2.15]; simultaneous: 1.94 [1.86;2.03]. Among the 26,396 adults with CRS in 2012, 11,355 (43.0%) had T2DM and were younger than non-diabetic adults (77.4 ± 9.5 versus 82.3 ± 10.0); 8,314 patients with T2DM were matched to 8,314 patients without. T2DM increased risk of: end-stage kidney disease, adjusted HR 1.50 [1.39;1.62]; myocardial infarction 1.35 [1.19;1.53]; cardiovascular death 1.20 [1.13;1.27]; heart failure 1.17 [1.12;1.21]; and all-cause death 1.09 [1.06;1.13], but not ischemic stroke. CONCLUSION: Patients with T2DM represent almost half of patients with CRS and are younger than their non-diabetic counterparts. T2DM doubles the risk of CRS and increases the risk of death, cardiovascular outcome, and end-stage kidney disease but not ischemic stroke after CRS.

Prevalence and incidence of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: A nationwide French observational study of hospitalized patients.

BACKGROUND: Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) increase risks of cardiovascular (CV) and renal disease compared with diabetes-free populations. There are only a few studies comparing T1DM and T2DM for the relative risk of these clinical events. METHODS: All adult patients hospitalized in French hospitals in 2013 with at least 5 years of follow-up were identified and categorized by their diabetes status. A total of 50,623 patients with T1DM (age 61.4 ± 18.6, 53% male) and 425,207 patients with T2DM (age 68.6 ± 14.3, 55% male) were followed over a median period of 5.3 years (interquartile range: 2.8 - 5.8 years). Prevalence and event rates of myocardial infarction (MI), heart failure (HF), ischemic stroke, chronic kidney disease (CKD), all-cause death and CV death were assessed with age stratification of 10-year intervals. For clinical events during follow-up, we report hazard ratios (HRs) in T1DM relative to T2DM. RESULTS: The age and sex-adjusted prevalence of CV diseases was higher in T2DM for ages above 40 years whereas the prevalence of CKD was more common in T1DM between ages 18 and 70 years. During 2,033,239 person-years of follow-up, age and sex-adjusted HR event rates comparing T1DM, versus T2DM as reference, showed that MI and HF relative risks were increased above 60 years (1.2 and 1.4 -fold). HR of ischemic stroke did not markedly differ between T1DM and T2DM. Risk of incident CKD was 2.4-fold higher in T1DM above 60 years. All-cause death HR risk was 1.1-fold higher in T1DM after 60 years and the CV death risk was 1.15-fold higher in T1DM between 60 and 69 years compared to T2DM. CONCLUSIONS: Although the crude prevalent burden of CV diseases may be lower in T1DM than in T2DM, patients with T1DM may have a higher risk of incident MI, HF, all-cause death and CV death above 60 years of age, highlighting the need for improved prevention in this population.

Concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in Human Serum and Adipose Tissues and Stimulatory Effect of Naphthalene in Adipogenesis in 3T3-L1 Cells.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity.

A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia.

Genetic diagnosis of familial hypercholesterolemia (FH) remains unexplained in 30 to 70% of patients after exclusion of monogenic disease. There is now a growing evidence that a polygenic burden significantly modulates LDL-cholesterol (LDL-c) concentrations. Several LDL-c polygenic risk scores (PRS) have been set up. However, the balance between their diagnosis performance and their practical use in routine practice is not clearly established. Consequently, we set up new PRS based on our routine panel for sequencing and compared their diagnostic performance with previously-published PRS. After a meta-analysis, four new PRS including 165 to 1633 SNP were setup using different softwares. They were established using two French control cohorts (MONA LISA n=1082 and FranceGenRef n=856). Then the explained LDL-c variance and the ability of each PRS to discriminate monogenic negative FH patients (M-) versus healthy controls were compared with 4 previously-described PRS in 785 unrelated FH patients. Between all PRS, the 165-SNP PRS developed with PLINK showed the best LDL-c explained variance (adjusted R²=0.19) and the best diagnosis abilities (AUROC=0.77, 95%CI=0.74-0.79): it significantly outperformed all the previously-published PRS (p<1 × 10-4). By using a cut-off at the 75th percentile, 61% of M- patients exhibited a polygenic hypercholesterolemia with the 165-SNP PRS versus 48% with the previously published 12-SNP PRS (p =3.3 × 10-6). These results were replicated using the UK biobank. This new 165-SNP PRS, usable in routine diagnosis, exhibits better diagnosis abilities for a polygenic hypercholesterolemia diagnosis. It would be a valuable tool to optimize referral for whole genome sequencing.

Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

Yearly Incidence of Stroke and Bleeding in Atrial Fibrillation with Concomitant Hyperthyroidism: A National Discharge Database Study.

Background: Hyperthyroidism is associated with atrial fibrillation (AF), and the latter is a major risk factor for stroke. Aim: We aimed to investigate the yearly incidence of stroke and bleeding in AF patients with and without concomitant hyperthyroidism from the French National Hospital Discharge Database. Methods: Admissions with AF between January 2010 and December 2019 were retrospectively identified and retrieved from the French national database. Incidence rates of ischaemic stroke and bleeding were compared in AF patients with and without concomitant hyperthyroidism. The associations of risk factors with ischaemic stroke were assessed by Cox regression. Results: Overall 2,421,087 AF patients, among whom 32,400 had concomitant hyperthyroidism were included in the study. During the follow-up (mean: 2.0 years, standard deviation SD: 2.2 years), the yearly incidence of ischaemic stroke was noted to be 2.6 (95% confidence interval CI: 2.5−2.8) in AF patients with concomitant hyperthyroidism, and 2.3 (95%CI: 2.3−2.4) in non-thyroid AF patients. Hyperthyroidism was noted as an independent risk factor for ischaemic stroke (adjusted hazard ratio aHR: 1.133, 95%CI: 1.080−1.189) overall, particularly within the first year of hyperthyroidism diagnosis (aHR 1.203, 95%CI 1.120−1.291), however, the association became non-significant in subsequent years (aHR 1.047, 95%CI 0.980−1.118). Major bleeding incidence was lower in the hyperthyroid AF group in comparison to the non-thyroid AF group (incidence ratio: 5.1 vs. 5.4%/year, p < 0.001). The predictive value of CHA2DS2VASc and HAS-BLED scores for ischaemic stroke and bleeding events, respectively, did not differ significantly between AF patients with or without concomitant hyperthyroidism. Conclusions: Hyperthyroidism seems to be an independent risk factor of ischaemic stroke in AF patients, particularly within the first year of hyperthyroidism diagnosis.

The Hepatokine FGF21 Increases the Human Spermatozoa Motility.

Lifestyle, environment and excess body weight are not only associated with an increased risk of metabolic disorders, such as type 2 diabetes, but also to other pathological processes, such as infertility. A hormone produced mainly by the liver called fibroblast growth factor 21 (FGF21) is closely linked to the energy status and is increased in patients suffering from obesity or insulin resistance. Recently, FGF21 has been shown to be associated with female fertility disorders, but no or few data about the role of FGF21 on human male fertility has been described. In the present study, FGF21 was measured in the seminal fluid at a lower level in comparison to the blood level. Thus, in the present in vitro study, we aimed to decipher the FGF21 system in human semen. To evaluate the putative role of FGF21 on spermatozoa function, we incubated human spermatozoa with increasing concentrations of recombinant human FGF21. The FGF21 in seminal fluid is potentially produced by male reproductive tract tissues. In spermatozoa, the FGF21 signal was transduced by the two main receptors FGFR1-c and FGFR3 and the cofactor ß-klotho, which are colocalized in the middle piece of spermatozoa and stimulated the PI3K/Akt and MAPK pathways. Finally, in vitro treatment by FGF21 significantly increased sperm motility and ATP levels. Concomitantly, exposure to FGF21 improved the oxidative stress, as a lower ROS level was observed. Overall, these results seem to indicate that the metabolic factor, FGF21, positively modifies the activity and quality of the parameters of human spermatozoa.

Metabolically healthy obesity and cardiovascular events: A nationwide cohort study.

AIM: To evaluate the associations between metabolically healthy obesity (MHO) and different types of incident cardiovascular events in a contemporary population. MATERIALS AND METHODS: All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and without a history of major adverse cardiovascular event (MACE; myocardial infarction, heart failure [HF], ischaemic stroke or cardiovascular death [MACE-HF]) or underweight/malnutrition were identified. They were categorized by phenotypes defined by obesity and three metabolic abnormalities (diabetes, hypertension and hyperlipidaemia). Hazard ratios (HRs) for cardiovascular events during follow-up were adjusted on age, sex and smoking status at baseline. RESULTS: In total, 2 873 039 individuals were included in the analysis, among whom 272 838 (9.5%) had obesity. During a mean follow-up of 4.9 years, when pooling men and women, individuals with MHO had a higher risk of MACE-HF (multivariate-adjusted HR 1.22, 95% confidence interval [CI]: 1.19-1.24), new-onset HF (HR 1.34, 95% CI 1.31-1.37) and atrial fibrillation (AF; HR 1.33, 95% CI 1.30-1.37) compared with individuals with no obesity and zero metabolic abnormalities. By contrast, risks were not higher for myocardial infarction (HR 0.92, 95% CI 0.87-0.98), ischaemic stroke (HR 0.93, 95% CI 0.88-0.98) and cardiovascular death (HR 0.99, 95% CI 0.93-1.04). MHO in men was associated with a higher risk of clinical events compared with metabolically healthy men of normal weight (HR 1.12-1.80), while women with MHO had a lower risk for most events than metabolically healthy women of normal weight (HR 0.49-0.99). CONCLUSIONS: In a large and contemporary analysis of patients seen in French hospitals, individuals with MHO did not have a higher risk of myocardial infarction, ischaemic stroke or cardiovascular death than metabolically healthy individuals with no obesity. By contrast, they had a higher risk of new-onset HF and new-onset AF. However, notable differences were observed in men and women in the sex-stratified analysis.

[How a metabolic hormone, FGF21 (fibroblast growth factor 21) impacts reproduction]. / Impact du FGF21, une hormone du métabolisme énergétique, sur la reproduction.

Obesity or insulin resistance are the major non-infectious diseases that continue to progress worldwide. They promote diabetes and cardiovascular diseases, but also lead to a decrease in fertility in both sexes. FGF21, discovered in the 2000s, is a hormone closely linked to the energy status and has the ability to decrease insulin resistance. Its action through the FGFR1c, 3c & 4 receptors modulates tissues involved in energy-related metabolism but also the brain and the gonads. Recent data favor a role of FGF21 in female and male fertility, but raise the question about the role of FGF21 on reproductive function. In this review, we have scanned the different FGF21 actions on the reproductive axis, suggesting a potential therapeutic role in case of infertility.

TITLE: Impact du FGF21, une hormone du métabolisme énergétique, sur la reproduction. ABSTRACT: L'obésité et l'insulinorésistance sont les principales maladies non infectieuses qui progressent le plus dans le monde. Elles favorisent l'hypertension, les maladies cardio-vasculaires, mais conduisent aussi à une chute de la fertilité dans les deux sexes. Le FGF21, découvert dans les années 2000, est lié au statut énergétique de l'organisme et améliore l'insulinorésistance. Via ses récepteurs (FGFR1c, 3c,et 4), il agit sur le foie et au niveau d'organes régulant le métabolisme glucido-lipidique, mais aussi sur le cerveau et les gonades. Des données récentes sont ainsi en faveur d'un rôle régulateur de FGF21 sur la fertilité, tant féminine que masculine. Mais quel rôle FGF21 peut-il jouer dans la reproduction ? Dans cette revue, nous avons examiné les différentes activités que présente cette hormone sur la reproduction, ouvrant la voie à une éventuelle utilisation thérapeutique en cas d'infertilité.

Impact of gender on relative rates of cardiovascular events in patients with diabetes.

AIM: To investigate whether diabetes confers higher relative risks of cardiovascular events in women compared with men using contemporary data and also whether such gender-differences are dependent on age. METHODS: All patients discharged from French hospitals in 2013 with at least 5 years of follow-up and no history of major adverse cardiovascular events including heart failure (MACE-HF; heart failure, myocardial infarction, ischaemic stroke, cardiovascular death) were identified and categorized by diabetes status. Overall and age-stratified incidence rates, hazard ratios (HRs) and women-to-men ratios (WMRs) for MACE-HF leading to hospitalization were also calculated. Adjustments were then made for age and baseline characteristics according to cardiovascular risk factors and non-cardiovascular comorbidities. RESULTS: The study included 2,953,816 subjects, among whom 349,928 (11.9%) had diabetes. Of those with diabetes, the absolute rate of MACE-HF was higher in men than in women (96 vs 66 per 1000 person-years); corresponding absolute rates in men and women without diabetes were 44 vs 27 per 1000 person-years. Comparing those with and without diabetes, women had a higher unadjusted HR of MACE-HF (2.45, 95% CI: 2.42-2.47) than men (2.15, 95% CI: 2.14-2.17), with an adjusted WMR of 1.13 (95% CI: 1.12-1.15). HRs of MACE-HF related to diabetes were highest in women aged around 45 years and in the youngest men and decreased with advancing age in both these groups. However, HRs were higher in women of all ages > 40 years. After adjustment, this effect was more apparent for myocardial infarction (adjusted WMR: 1.43, 95% CI: 1.38-1.48) than for either ischaemic stroke (adjusted WMR: 1.10, 95% CI: 1.07-1.14) or heart failure (adjusted WMR: 1.13, 95% CI: 1.11-1.14). CONCLUSION: Although men have higher absolute risks of cardiovascular complications, the relative risks of cardiovascular complications associated with diabetes are higher in women than in men.

Sex, age, type of diabetes and incidence of atrial fibrillation in patients with diabetes mellitus: a nationwide analysis.

BACKGROUND: There remain uncertainties regarding diabetes mellitus and the incidence of atrial fibrillation (AF), in relation to type of diabetes, and the interactions with sex and age. We investigated whether diabetes confers higher relative rates of AF in women compared to men, and whether these sex-differences depend on type of diabetes and age. METHODS: All patients aged ≥ 18 seen in French hospitals in 2013 with at least 5 years of follow-up without a history of AF were identified and categorized by their diabetes status. We calculated overall and age-dependent incidence rates, hazard ratios, and women-to-men ratios for incidence of AF in patients with type 1 and type 2 diabetes (compared to no diabetes). RESULTS: In 2,921,407 patients with no history of AF (55% women), 45,389 had prevalent type 1 diabetes and 345,499 had prevalent type 2 diabetes. The incidence rates (IRs) of AF were higher in type 1 or type 2 diabetic patients than in non-diabetics, and increased with advancing age. Among individuals with diabetes, the absolute rate of AF was higher in men than in women. When comparing individuals with and without diabetes, women had a higher adjusted hazard ratio (HR) of AF than men: adjusted HR 1.32 (95% confidence interval 1.27-1.37) in women vs. 1.12(1.08-1.16) in men for type 1 diabetes, adjusted HR 1.17(1.16-1.19) in women vs. 1.10(1.09-1.12) in men for type 2 diabetes. CONCLUSION: Although men have higher absolute rates for incidence of AF, the relative rates of incident AF associated with diabetes are higher in women than in men for both type 1 and type 2 diabetes.

Energy sensors and reproductive hypothalamo-pituitary ovarian axis (HPO) in female mammals: Role of mTOR (mammalian target of rapamycin), AMPK (AMP-activated protein kinase) and SIRT1 (Sirtuin 1).

In female, energy metabolism influences reproductive function by modulating the Hypothalamic Pituitary Ovarian axis including the hypothalamic GnRH neuronal network, the pituitary gonadotropin secretion and the ovarian follicle growth and steroidogenesis. Several hormones and neuropeptides or metabolites are important signals between energy balance and reproduction. These energy sensors mediate their action on reproductive cells through specific kinases or signaling pathways. This review focuses on the role of three main enzymes-specifically, mTOR, AMPK, and SIRT1 at the hypothalamic pituitary and ovarian axis in normal female fertility and then we discuss their possible involvement in some women reproductive disorders known to be associated with metabolic complications, such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF).

Association between sleep disturbances, fear of hypoglycemia and psychological well-being in adults with type 1 diabetes mellitus, data from cross-sectional VARDIA study.

AIM: To assess the relationship between sleep quality, fear of hypoglycemia, glycemic variability and psychological well-being in type 1 diabetes mellitus. METHODS: Our data were provided by the VARDIA Study, a multicentric cross-sectional study conducted between June and December 2015. Sleep characteristics were assessed by the Pittsburgh Sleep Quality Index (PSQI). Fear of hypoglycemia and psychological well-being were measured with the Hypoglycemia Fear Survey version II (HFS-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Glycemic variability (GV) was determined using the CV of three 7-point self-monitoring blood glucose profiles and the mean amplitude of glycemic excursion (MAGE). RESULTS: 315 patients were eligible for PSQI questionnaire analysis: 54% women, mean age 47 ± 15, mean diabetes duration of 24 ± 13 years, HbA1c of 7.6 ± 0.9% (60 ± 7,5mmol/mol). Average PSQI score was 6.0 ± 3.3 and 59.8% of the patients had a PSQI score > 5. HFS-II score and HADS were significantly higher among "poor" sleepers (p < 0.0001) and PSQI score was positively associated with HADS (ß = 0.22; 95% CI = 0.08;0.35). GV evaluated by CV or MAGE did not differ between "poor" and "good" sleepers (p = 0.28 and 0.54, respectively). CONCLUSIONS: Adult patients with type 1 diabetes have sleep disturbances which correlate with psychological well-being. This study suggests that psychological management can be a target to improve sleep quality in adults with type 1 diabetes mellitus.

Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models.

It is well known that adipokines are endocrine factors that are mainly secreted by white adipose tissue. Their central role in energy metabolism is currently accepted. More recently, their involvement in fertility regulation and the development of some reproductive disorders has been suggested. Data concerning the role of leptin and adiponectin, the two most studied adipokines, in the control of the reproductive axis are consistent. In recent years, interest has grown about some novel adipokines, chemerin, visfatin, resistin and apelin, which have been found to be strongly associated with obesity and insulin-resistance. Here, we will review their expression and role in male and female reproduction in humans and animal models. According to accumulating evidence, they could regulate the secretion of GnRH (Gonadotropin-Releasing Hormone), gonadotropins and steroids. Furthermore, their expression and that of their receptors (if known), has been demonstrated in the human and animal hypothalamo-pituitary-gonadal axis. Like leptin and adiponectin, these novel adipokines could thus represent metabolic sensors that are able to regulate reproductive functions according to energy balance changes. Therefore, after investigating their role in normal fertility, we will also discuss their possible involvement in some reproductive troubles known to be associated with features of metabolic syndrome, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia and intra-uterine growth retardation in women, and sperm abnormalities and testicular pathologies in men.

No association between fear of hypoglycemia and blood glucose variability in type 1 diabetes: The cross-sectional VARDIA study.

AIMS: In type 1 diabetes (T1D), treatment efficacy is limited by the unpredictability of blood glucose results and glycemic variability (GV). Fear of Hypoglycemia (FOH) remains a major brake for insulin treatment optimization. We aimed to assess the association of GV with FOH in participants with T1D in an observational cross-sectional study performed in 9 French Diabetes Centres (NCT02790060). METHODS: Participants were T1D for ≥5 years, aged 18-75 years, on stable insulin therapy for ≥3 months. The coefficient of variation (CV) of blood glucose and mean amplitude of glycemic excursions (MAGE) were used to assess GV from 7-point self-monitoring of blood glucose (SMBG). FOH was assessed using the validated French version of the Hypoglycemia Fear Survey-II (HFS-II) questionnaire. RESULTS: Among a total of 570 recruited participants, 298 were suitable for analysis: 46% women, 58% on continuous subcutaneous insulin infusion [CSII], mean age 49 ±â€¯16 years, HbA1c 7.5 ±â€¯0.9%, HFS-II score 67 ±â€¯18 and 12% with recent history of severe hypoglycemia during the previous 6 months, mean CV 39.8 ±â€¯9.7% and MAGE 119 ±â€¯42 mg/dL. CV and MAGE did not significantly correlate with HFS-II score (R = -0.05;P = 0.457 and R = 0.08;P = 0.170). Participants with severe hypoglycemia in the previous 6 months had higher HFS scores. Participants with higher HFS scores presented more hypoglycemias during follow-up. CONCLUSIONS: FOH as determined using the HFS-II questionnaire was not associated with 7-point SMBG variability in participants with T1D, but was associated with a positive history of severe hypoglycemia. Higher FOH was associated with higher frequency of hypoglycemia during follow-up.