Polymorphisms in GC and NADSYN1 Genes are associated with vitamin D status and metabolic profile in Non-diabetic adults.

BACKGROUND: Our aim was to assess the associations between vitamin D (vitD) status, metabolic profile and polymorphisms in genes involved in the transport (Group-Component: GC) and the hydroxylation (NAD synthetase 1: NADSYN1) of 25 hydroxyvitamin D (25(OH)D) in non-diabetic individuals. METHODS: We conducted a cross-sectional study with 323 individuals recruited from the Health Center of Guadeloupe, France. The rs2282679 T > G and rs2298849 T > C in GC and rs12785878 G > T in NADSYN1 were genotyped. RESULTS: Mean age was 46(range 18-86) years. 57% of participants had vitD insufficiency, 8% had vitD deficiency, 61% were overweight and 58% had dyslipidemia. A higher frequency of overweight was noted in women carrying rs2298849T allele v CC carriers (71% v 50%; P = 0.035). The rs2282679G allele was associated with increased risks of vitD deficiency and vitD insufficiency (OR =3.53, P = 0.008, OR = 2.34, P = 0.02 respectively). The rs2298849 TT genotype was associated with vitD deficiency and overweight (OR =3.4, P = 0.004 and OR = 1.76, P = 0.04 respectively) and the rs12785878 GG genotype with vitD insufficiency and dyslipidemia (OR = 1.80, P = 0.01 and OR = 1.72, P = 0.03 respectively). Based on the number of risk alleles for rs2282679 and rs12785878 combined, a genotype score of 3 (vs. 0-1) was associated with a 5.5 ng/mL average reduction in serum 25(OH)D levels (P = 0.001). CONCLUSIONS: The GC and NADSYN1 genes are associated with the vitamin D status and might contribute to dyslipidemia and overweight independently of 25(OH)D levels.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. METHODS: ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled ß-galactosidase gene (Ad-RSV-ß-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. RESULTS: VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. CONCLUSIONS: The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury.

Metabolic Syndrome Components in a Nondiabetic Afro-Caribbean Population: Influence of Gender and Age.

Background: Our aim was to describe the prevalence of metabolic syndrome (MetS) and its components among Afro-Caribbean adults without diabetes and cardiovascular complications. Methods: Participants were recruited from a Health Center in Guadeloupe, French West Indies. MetS was defined according to the NCEP ATP III. Prevalence of MetS and MetS components were compared across age groups and sex. The odds ratios (ORs) and 95% confidence intervals were obtained using logistic regression. Results: There were 1011 participants (68.8% women, mean age 47.8 ± 11.8 years). Prevalence of MetS was 17.9% (21.1% women, 10.8% men) and increased by age in women. High blood pressure had the highest prevalence among men and among women ≥60 years. Prevalence of abdominal obesity (AbO) was higher in women than in men. High triglyceride levels were uncommon at all ages and, men and women <40 years, compared with the other groups had higher prevalence of low high-density lipoprotein cholesterol (HDL-C) levels. With multiple logistic regression, compared with adults <40 years, those ≥60 years had the highest OR for prevalent hypertension 7.8 (4.8-12.8); P < 0.001, AbO 2.1 (1.3-3.3); P = 0.002 and high fasting blood glucose levels 5.5 (3.1-9.8); P < 0.001. They also had lower odds for having low HDL-C than the younger ones (G1: age <40 years). Among persons ≥60 years, OR for MetS was 1.9 (1.1-3.6); P = 0.013 compared with the referent group. Compared with men, women had higher odds of MetS 2.2 (1.5-3.3); P < 0.001. Conclusion: Women were more likely to have MetS than men and persons ≥60 years were significantly more likely to have MetS than persons <40 years. Preventive measures are required to reduce the prevalence of MetS.

N-terminal Pro-B-Type Natriuretic Peptide and Malnutrition in Patients on Hemodialysis.

Natriuretic peptides, brain natriuretic peptide (BNP), and N-terminal probrain natriuretic peptide (NT-proBNP) are mainly known as diagnostic markers for heart failure with high diagnostic and prognostic values in the general population. In patients who are undergoing hemodialysis (HD), changes in NT-proBNP can be related to noncardiac problems such as fluid overload, inflammation, or malnutrition and can also be influenced by the dialysis characteristics. The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients. Articles published after 2009 and over a ten-year period were considered for inclusion. We first briefly discuss the traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in HD patients. Mechanisms that could explain these relationships were also discussed. Overall, 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects were taken into account. NT-proBNP levels correlated with several factors described in the 4 categories of markers indicative of PEW (body mass and composition, muscle mass, biochemical criteria, and dietary intakes) and/or were associated with PEW. Interactions between several parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status. NT-proBNP is elevated in HD patients and is associated with malnutrition. Nevertheless, the prognostic value of NT-proBNP on nutritional status should be evaluated.

Influence of K656N Polymorphism of the Leptin Receptor Gene on Obesity-Related Traits in Nondiabetic Afro-Caribbean Individuals.

Background: Ethnic variations have been reported in allelic frequencies of the leptin receptor gene (LEPR) with population-specific effects. We aimed to explore the association of LEPR polymorphisms with obesity, metabolic syndrome (MetS), and leptin levels in Afro-Caribbean nondiabetic subjects. Methods: Genotypic analysis of three LEPR polymorphisms (K109R, Q223R, and K656N) was performed using TaqMan allelic discrimination assays. Associations were measured with phenotypic variables, including body mass index (BMI), waist circumference (WC), and leptin levels. Linear and logistic regressions were performed to evaluate the effects of single-nucleotide polymorphisms (SNPs). Results: Mean age was 46 ± 12 years. Among the 375 participants, 29.3% were obese, 36.3% had abdominal obesity, and 18.1% had MetS. Significant association between BMI (P < 0.002) and WC (P < 0.005) was observed for K656N, whereas the associations were not statistically significant for the other two SNPs. No association was found with leptin levels for the three SNPs. The variant allele frequencies for LEPR 109R, 223R, and 656N were 0.16, 0.46, and 0.20, respectively. In dominant models, the variant allele 656N (GC/CC vs. GG) was associated with prevalence of obesity [odds ratio (OR) 1.82; P = 0.012] and abdominal obesity (OR 2.00; P = 0.007), but not significantly with prevalence of MetS (OR 1.72; P = 0.029). Individuals carrying four variant alleles of the three SNPs had a significantly higher risk of obesity (OR 2.86; P = 0.032) than those carrying none variant allele. Conclusion: Our results suggest an influence of K656N polymorphism in the LEPR gene on obesity and abdominal obesity in this Afro-Caribbean population.

High Prevalence of Rare Monogenic Forms of Obesity in Obese Guadeloupean Afro-Caribbean Children.

Context: The population of Guadeloupe Island exhibits a high prevalence of obesity. Objective: We aimed to investigate whether rare genetic mutations in genes involved in monogenic obesity (or diabetes) might be causal in this population of Afro-Caribbean ancestry. Design and Setting: This was a secondary analysis of a study on obesity conducted in schoolchildren from Guadeloupe in 2013 that aimed to assess changes in children's profiles after a lifestyle intervention program. Through next-generation sequencing, we sequenced coding regions of 59 genes involved in monogenic obesity or diabetes in participants from this study. Participants and Interventions: A total of 25 obese schoolchildren from Guadeloupe were screened for rare mutations (nonsynonymous, splice-site, or insertion/deletion) in 59 genes. Main Outcome Measures: Correlation between phenotypes and mutations of interest. Results: We detected five rare heterozygous mutations in five different children with obesity: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutations in ABCC8 (p.Lys1521Asn and p.Ala625Val) or KCNJ11 (p.Val13Met and p.Val151Met) that were of uncertain significance. Conclusions: We were able to detect pathogenic or likely pathogenic mutations linked to severe obesity in >15% of this population, which is much higher than what we observed in Europeans (∼5%).

NT-proBNP, Cardiometabolic Risk Factors, and Nutritional Status in Hemodialysis Patients.

BACKGROUND: We aimed to evaluate the association between NT-proBNP and malnutrition in HD patients while taking into account the four established categories of parameters for diagnosis of protein energy wasting (PEW). METHODS: A cross-sectional study was performed in Afro-Caribbean dialysis patients. One component in each of the 4 categories for the wasting syndrome was retained: serum albumin ≤ 38 g/L, BMI ≤ 23 Kg/m2, serum creatinine ≤ 818 µmol/L, and normalized protein catabolic rate (nPCR) ≤ 0.8 g/kg/day. NT-proBNP was assessed using a chemiluminescence immunoassay. Two multivariate logistic regression models were performed to determine the parameters associated with high NT-proBNP concentrations. RESULTS: In 207 HD patients, 16.9% had PEW (at least three components). LVEF lower than 60% was found in 13.8% of patients. NT-proBNP levels ranged from 125 to 33144 pg/mL. In model 1, high levels of NT-proBNP (≥6243 pg/mL) were independently associated with PEW OR 14.2 (3.25-62.4), male gender 2.80 (1.22-6.57), hsCRP > 5 mg/L 3.90 (1.77-8.57), and dialysis vintage > 3 years 3.84 (1.35-10.8). In model 2, LVEF OR was 0.93 (0.88-0.98). NT-proBNP concentrations were significantly higher when the PEW component number was higher. CONCLUSION: In dialysis patients, high NT-proBNP levels must draw attention to cardiac function but also to nutritional status.

Influence of Genetic Risk Factors on Coronary Heart Disease Occurrence in Afro-Caribbeans.

BACKGROUND: Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. METHODS: We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. RESULTS: In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). CONCLUSIONS: This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution.

Gene Polymorphisms of FABP2, ADIPOQ and ANP and Risk of Hypertriglyceridemia and Metabolic Syndrome in Afro-Caribbeans.

OBJECTIVES: The metabolic syndrome (MetS) is a cluster of metabolic abnormalities and cardiovascular risk factors that are highly heritable and polygenic. We investigated the association of allelic variants of three candidate genes, rs1799883-FABP2, rs1501299-ADIPOQ and rs5065-ANP with MetS and its components, individually and in combination, using a genetic risk score. METHODS: A cross-sectional study was conducted in 462 Afro-Caribbeans subjects without cardiovascular complications or lipid-lowering medications. Cardiovascular risk factors and MetS components (NCEP-ATPIII criteria) were recorded. The 3 SNPs were genotyped. The genetic risk score was calculated by summing the number of risk alleles at each locus. Logistic regressions were used. RESULTS: Fifty-eight participants (12.6%) were diabetics and 116 (25.1%) had a MetS. In a dominant model, rs1799883 was associated with hypertriglyceridemia (OR 2.22; P = 0.014) and hypertriglyceridemic waist (HTGW), (P = 0.014) but not significantly with overweight (P = 0.049), abdominal obesity (P = 0.033) and MetS (P = 0.068). In a dominant model, the OR of MetS and HTGW for rs1501299 were 1.80 (P = 0.028) and 2.19 (P = 0.040) respectively. In a recessive model, the OR of hypertriglyceridemia for rs5065 was 1.94 (P = 0.075). The genetic risk score was significantly associated with MetS. Subjects carrying 4-5 risk alleles (18.8%) had a nearly 2.5-fold-increased risk of MetS compared to those carrying 0-1 risk allele (24.3%): OR 2.31; P = 0.025. CONCLUSIONS: This study supports the association of FABP2, ANP and ADIPOQ gene variants with MetS or its components in Afro-Caribbeans and suggests a cumulative genetic influence of theses variants on this syndrome and a potential effect on lipid metabolism.

Vitamin D Status, Insulin Resistance, Leptin-To-Adiponectin Ratio in Adolescents: Results of a 1-Year Lifestyle Intervention.

AIM: We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program. METHODS: 25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity. RESULTS: Among 117 girls and boys (11-15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels < 20 ng/mL). With linear regression models where 25(OH)D and HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P < 0.001 for all). After one year, in 78 children/adolescent, mean serum 25(OH)D increased significantly from 21.4 ± 4.9 ng/mL at baseline to 23.2 ± 6.0 after 1 year; P = 0.003 whereas BMI z-score, HOMA-IR and L/A ratio decreased significantly (P = 0.003, P < 0.001 and P = 0.012; respectively). CONCLUSION: The association between 25(OH)D and HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status.

High pulse pressure associated with cardiovascular events in patients with type 2 diabetes undergoing hemodialysis.

BACKGROUND: The aims of this study were to examine systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) in patients with type 2 diabetes undergoing hemodialysis (HD), and to assess the relationships between these parameters and cardiovascular (CV) events such as coronary heart disease and congestive cardiac failure. METHODS: A total of 80 Afro-Caribbean type 2 diabetic patients undergoing hemodialysis in three centers in Guadeloupe, French West Indies, were included in this cross-sectional study. Pre- and postdialysis BP were recorded. Logistic regression methods and areas under the receiver operating characteristic curves were used. RESULTS: The mean age (+/- standard deviation) was 62.2 years (+/-10.2 years). A total of 24 subjects (30%) had one or more CV events. Sixteen (20%) had coronary disease, 15 (18.8%) cardiac failure, and seven (8.8%) had both. The medians [interquartile ranges] for predialysis PP was higher in patients with CV comorbidity than in patients without a history of CV at 84.5 mm Hg [74.5 to 92.3]v 69.5 mm Hg [61.0 to 79.5], P = .003. Areas under the ROC curves (95% confidence intervals) predialysis were significant only for SBP and PP at 0.70 (0.58 to 0.82) v 0.71 (0.59 to 0.83) without statistical differences. After adjustment for gender, age, body mass index, antihypertensive use, time on hemodialysis (>or=2 years), and hemoglobin rate, the odds ratio was significant only predialysis, and a higher odds ratio was found for PP at 2.25 (1.22 to 4.18), P = .01, than for SBP 1.97 (1.12 to 3.49), P = .02. CONCLUSIONS: Our results suggest that the strongest association of PP with CV morbidities should be considered in therapeutic strategies. These results show the necessity of targeting antihypertensive treatment to patients' predialysis blood pressure values.

Impact of protein energy wasting status on survival among Afro-Caribbean hemodialysis patients: a 3-year prospective study.

BACKGROUND: We assessed the prognostic value of protein-energy wasting (PEW) on mortality in Afro-Caribbean MHD patients and analysed how diabetes, cardiovascular disease (CVD) and inflammation modified the predictive power of a severe wasting state. METHOD: A 3-year prospective study was conducted in 216 patients from December 2011. We used four criteria from the nomenclature for PEW proposed by the International Society of Renal Nutrition and Metabolism in 2008: serum albumin 38 g/L, body mass index (BMI) ≤23 kg/m(2), serum creatinine ≤818 µmol/L and protein intake assessed by nPCR ≤0.8 g/kg/day. PEW status was categorized according the number of criteria. Cox regression analyses were used. RESULTS: Forty deaths (18.5 %) occurred, 97.5 % with a CV cause. Deaths were distributed as follows: 7.4 % in normal nutritional status, 13.2 % in slight wasting (1 PEW criterion), 28 % in moderate wasting (2 criteria) and 50 % in severe wasting (3-4 criteria). Among the PEW markers, low serum albumin (HR 3.18; P = 0.001) and low BMI (HR 1.97; P = 0.034) were the most significant predictors of death. Among the PEW status categories, moderate wasting (HR 3.43; P = 0.021) and severe wasting (HR 6.59; P = 0.001) were significant predictors of death. Diabetes, CVD, and inflammation were all additives in predicting death in association with severe wasting with a strongest HR (7.76; P < 0.001) for diabetic patients. CONCLUSIONS: The nomenclature for PEW predicts mortality in our Afro-Caribbean MHD patients and help to identify patients at risk of severe wasting to provide adequate nutritional support.

Ghrelin, adipokines, metabolic factors in relation with weight status in school-children and results of a 1-year lifestyle intervention program.

BACKGROUND: Overweight in Guadeloupe is a public health matter affecting children and adults. In the present study we evaluated the metabolic profile, including serum ghrelin, leptin and adiponectin levels, in normal weight, overweight and obese school children and we analyzed the potential changes in anthropometric and metabolic risk factors after a 1-year lifestyle intervention program. METHODS: Parameters were assessed at baseline and at 1 year. Three groups (G) were defined according the International Obesity Task Force reference values, G1: normal weight / G2: overweight / G3: obese. The lifestyle intervention included dietary counseling, regular physical activity and family support. RESULTS: A total of 120 children (G1: n = 44, G2: n = 39, G3: n = 37), aged 11- 15 years and 59 % girls were enrolled. Obese children showed significant lower HDL-C, adiponectin and ghrelin concentrations, higher triglycerides, fasting blood glucose, insulin and leptin levels and also higher frequencies of abdominal obesity (G1: 2.3 %, G2: 28.2 %, G3: 73 %) and insulin resistance (GI: 39 %, G2: 72 %, G3: 89 %) than the other groups. In the overall sample, the linear regressions exploring the associations of ghrelin, adiponectin and leptin with age, gender, BMI z-score, HOMA-IR and tanner stage as independent variables showed strong associations of leptin levels with weight status and insulin resistance at baseline. The models accounted for 58 % of variability in leptin levels compared with 26 and 15 % for adiponectin and ghrelin levels respectively. In 83 children who completed the program, significant decreases in BMI z-score in overweight and obese children were noted. Leptin levels decreased significantly only in the obese group whereas adiponectin concentrations increased significantly in the three groups, In obese children, a significant correlation was found between changes in BMI Z-score, and changes in leptin levels (r = 0.39; P = 0.049) but not with changes in adiponectin levels. CONCLUSIONS: Abdominal obesity and insulin resistance were highly prevalent in obese children highlighting their risk of metabolic complications in adulthood. A 1-year long lifestyle intervention was associated with improvement in BMI z-score and metabolic parameters.

Body mass index (BMI) and waist circumference (WC) as screening tools for cardiovascular risk factors in Guadeloupean women.

Hypertension, dyslipidemia and type 2 diabetes, important cardiovascular risk factors, are strongly linked to obesity. Body mass index (BMI) and waist circumference (WC) are measures of obesity that can be useful in identifying individuals with these risk factors. We assessed which of the two measures is more informative at the population level. The study population included 5,149 consecutive women aged 18 to 74 recruited in an Health Center of Guadeloupe (FWI) in 1999. The areas under the ROC curves of BMI and WC and their 95% CI were computed and compared. Logistic regression analysis of BMI and WC and the areas under the ROC curves in two separate age groups (18-39 years and 40-74 years) showed that age modifies the discriminant ability of these parameters in identifying the CVD risk factors. Sensitivity equalled specificity at levels between 52-70% for BMI and 55-80% for WC. ROC areas for identifying each risk factors by BMI varied from 0.52 to 0.84 and by WC from 0.55 to 0.88. For the identifying of women with at least one CVD risk factor, in the whole population, the areas under the curves for BMI and WC (respectively, 0.71; 95% CI: 0.69-0.73 and 0.76; 95% CI: 0.74-0.78) were both significantly greater than 0.5. The difference between these correlated areas was 0.04, 95% CI [-0.05, -0.03]. The lowest values of the areas were noted in detecting women with dyslipidemia and the highest in detecting those with type 2 diabetes. Waist circumference, a practical tool that had a higher discriminant ability than BMI in identifying presence or absence of all these risk factors, appears as the best screening tool in this population.

Distribution of coronary artery disease severity and risk factors in Afro-Caribbeans.

BACKGROUND: Traditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups. AIMS: In this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity. METHODS: We retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score. RESULTS: In the studied population (mean age 64.7 ± 12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01-2.33; P=0.048), 1.61 (1.02-2.55; P=0.043) and 1.68 (1.11-2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29-0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor. CONCLUSION: Diabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention.

Adiponectin gene variants, adiponectin isoforms and cardiometabolic risk in type 2 diabetic patients.

AIMS/INTRODUCTION: The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (-11391G>A) and rs182052 (-10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry. MATERIALS AND METHODS: A cross-sectional study of 200 patients was carried out. Concentrations of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms were measured. The four polymorphisms were genotyped. RESULTS: Decreased values were noted for total Ad in overweight, dyslipidemia and coronary artery disease (CAD), for HMW in overweight and dyslipidemia, for MMW in CAD, for LMW in dyslipidemia and CAD, for the percentage HMW/total in overweight, and for MMW:HMW ratio in patients without hypertriglyceridemic waist (HTGW). Significant associations were noted between total Ad, HMW, and HMW/total Ad and rs182052 under a dominant model (P = 0.04, P = 0.03 and P = 0.04, respectively), and between MMW and rs17300539 (P = 0.006). No significant difference in adiponectin concentrations was noted according to rs2241766 and rs1501299 genotypes. Patients carrying the rs2241766 G allele (TG+GG) had an increased risk of HTGW (odds ratio [OR] 3.1; P = 0.04) and of CAD (OR 3.3; P = 0.01). The odds of having low total adiponectin concentrations (<25th percentile: 3.49 ng/mL) for carrying the rs182052A allele (AA+GA) was: OR 0.40; P = 0.009. The single-nucleotide polymorphism associated with adiponectin levels was not concomitantly associated with cardiometabolic risk factors. CONCLUSIONS: Adiponectin concentrations and ADIPOQ variants are implicated in the pathophysiological process leading to cardiovascular diseases, but the genetic effects seem to be independent of adiponectin concentrations in our Afro-Caribbean diabetic patients.

Are G3 ENETS neuroendocrine neoplasms heterogeneous?

The new WHO classification of gastroenteropancreatic (GEP) neuroendocrine tumors (NET) implies that G3 neoplasms with mitotic index >20 and/or Ki67 index >20% are neuroendocrine carcinomas (NEC), described as poorly differentiated, small or large cell types, by analogy with lung NEC. To characterize the subgroup of non-small-cell-type GEP and thoracic NET with mitotic index >20 and/or Ki67 >20% according to their pathological features, response to cisplatin and overall survival (OS). We reviewed pathological and clinical presentation of G3 non-small-cell-type NET referred to our institution for 5 years. Data from 166 patients with metastatic thoracic and GEP-NET were collected. Twenty-eight patients (17%) fulfill the inclusion criteria. Tumors were classified as well-differentiated NET (G3-WDNET) in 42.8% of cases and poorly differentiated, large-cell NEC (G3-LCNEC) in 57.2% of cases. Plasma chromogranin A or neuron-specific enolase were elevated in 42 and 25% respectively of G3-WDNET and 31 and 50% of G3-LCNEC. Somatostatin receptor scintigraphy was positive in 88 and 50% of G3-WDNET or G3-LCNEC respectively. Complete or partial response to cisplatin was observed in 31% of cases, all classified as G3-LCNEC. The median OS was 41 months for G3-WDNET but 17 months for G3-LCNEC (P=0.34). Short survival was observed in 25% of G3-WDNET but 62.5% of G3-LCNEC patients (P=0.049). G3 ENETS GEP and thoracic neuroendocrine neoplasms (NEN) could constitute a heterogeneous subgroup of NEN as regards diagnosis, prognosis, and treatment. If confirmed, future classifications may consider splitting them into two groups according to their morphological differentiation.

Vitamin D status in dark-skinned patients undergoing hemodialysis in a continually sunny country.

BACKGROUND: Vitamin D (vitD) insufficiency is common in end-stage renal disease. Seasonal and ethnic differences in vitD status have been reported previously. We hypothesized that vitD status in Afro-Caribbean patients on hemodialysis (HD) living in a country with a constant sunny climate would be better than that in African-American HD patients living in countries with a winter season. METHOD: A cross-sectional study was conducted in 152 Afro-Caribbean HD patients in a dialysis center located in Guadeloupe. We evaluated the prevalence of vitD insufficiency, defined as serum 25-hydroxyvitamin D (25(OH)D) levels below 30 ng/mL, compared with those results previously reported in African-American HD patients (88%). RESULTS: Prevalence of vitD insufficiency was 60% and thus lower than that in the African-American patients considered as the reference population (p<0.001). In our diabetic patients, this prevalence was 72.4%. Globally, 9.2% of patients had 25(OH)D below 15 ng/mL. Alfacalcidol therapy was prescribed in 29%. Mean 25(OH)D levels were higher in treated than in untreated patients (32 vs. 27 ng/mL; p=0.009). Patients with vitD insufficiency had dyslipidemia and diabetes more frequently. No significant differences were found between patients with and without vitD insufficiency for serum calcium, phosphorus and parathyroid hormone (PTH). In untreated patients, no significant correlation was found between 25(OH)D and PTH levels. CONCLUSION: Prevalence of vitD insufficiency in Afro-Caribbean HD patients was lower than that previously reported in African Americans undergoing HD in the United States. This finding may be due to the constantly sunny weather with a high intensity of UVB radiation in Guadeloupe.

Association of 2238T>C polymorphism of the atrial natriuretic peptide gene with coronary artery disease in Afro-Caribbeans with type 2 diabetes.

BACKGROUND: The atrial natriuretic peptide (ANP) is known mainly for its effects on kidney function and blood pressure homeostasis. We investigated the association between two ANP polymorphisms and pre-existing coronary artery disease (CAD) in patients of African descent with type 2 diabetes (T2D). METHODS: We conducted a cross-sectional and retrospective study of 218 volunteer Afro-Caribbean patients with T2D. Two polymorphisms (rs5064, 708C>T; and rs5065, 2238T>C) of ANP were genotyped using PCR-restriction fragment length polymorphism analysis. ANCOVA, χ2-test, and logistic regression were used for statistical analysis. RESULTS: Among these patients (92 men; 128 women), 67 (30.7%) had CAD, of whom 75% had had myocardial infarction. The frequency of rs5065-C carriers (TC/CC) was significantly lower in patients with CAD than in those without CAD (24 vs. 41%, P = 0.01). The frequency of hypertension did not differ significantly according to genotype. Univariate logistic regression revealed that male sex, age, dyslipidemia, hypertension, and rs5065-C carrier status were associated significantly with CAD. After adjustment for the variables of interest, the odds ratio (ORs) of CAD for rs5065-C carriers (TC/CC) was 0.50 (0.26-0.96; P = 0.038). No association was found between the rs5064 (708C>T) single-nucleotide polymorphisms (SNPs) and pre-existing CAD or cardiovascular risk factors. CONCLUSIONS: The ANP rs5065 (2238T>C) C allele seems to exert a protective effect against CAD in T2D patients of African descent. The relevance of ANP polymorphisms for CAD should be determined in different populations.

[Half of the patients with primary hyperparathyroidisms have a vitamin D deficiency: aggravating the osseous attack]. / La moitié des patients atteints d'hyperparathyroïdies primaires ont un déficit en vitamine D aggravant l'atteinte osseuse.

BACKGROUND: Primary hyperparathyroidism (PHPT) associates hypocalcemia and hypophosphatemia secondary to parathyroid hormone (PTH) excess. PHPT is asymptomatic for 80% of patients and responsible for a decrease in bone mineral density particularly in women. Vitamin D deficiency increases the risk of bone fractures. METHODS: We performed a prospective analysis of patients with PHPT in order to evaluate the prevalence of vitamin D deficiency. We determined the effects of vitamin D deficiency on bone metabolism: calcium, phosphate and PTH levels. We also analyzed biochemical markers of bone remodeling and bone mineral density (BMD) before and 6 months after vitamin D replacement. RESULTS: 75 patients with PHPT were identified: 38 patients with vitamin D deficiency but only 22 patients could be followed (G1). 14 patients with a normal level of vitamin D were followed (G2). Prevalence of vitamin D deficiency was 51%. Calcium and phosphate levels were similar into both groups. PTH levels were higher in the G1 group. Calciuria was significantly lower in the G1. For markers of bone formation (fragments of collagen CTX and alkaline phosphatase): osteocalcine levels were higher in G1 group. For bone resorption: télopeptides levels were significantly higher in the G1 group. T score was significantly lower in this group, favoring a significant osseous attack. After 6 months of substitution with vitamin D, calcium decreased and hypophosphatemia normalized. PTH levels decreased (-50.7%). Calciuria increased without risks of urinary lithiasis. Bone mineral density loss decreased while markers of bone turn over increased. DISCUSSION: Vitamin D deficiency increases the risk of bone fragility in PHPT. Few data are available in France concerning the prevalence of vitamin D deficiency in PHPT. Our results were similar to data in other countries. Vitamin D replacement with regular monitoring of calcium and calciuria levels is beneficial for metabolic and hormonal status, improves bone density, without systematic opposing effects. The follow-up of effectiveness by BMD could be associated with measurement of markers of bone remodeling. CONCLUSION: In asymptomatic PHPT, particularly those for which surgery is not indicated, measurement of 25 OH Vitamin D should be systematic. It is recommended before surgery.