First-degree Relatives Of Subjects Research Articles

The role of high fat diet on serum uric acid level among healthy male first degree relatives of type 2 diabetes mellitus

First-degree relatives (FDR) of type 2 diabetes mellitus have increased risk of developing insulin resistance-related disorders including hyperuricemia. We investigated metabolic profile and serum uric acid (SUA) metabolism in response to high-fat diet among healthy male FDR in comparison to those without family history of diabetes. A total of 30 FDR and 30 non-FDR subjects completed a 5-days-hypercaloric diet with fat added to regular daily intake. Despite similar insulin response, FDR displayed different changes in SUA compared to non-FDR subjects (0.26 ± 0.83 mg/dL vs − 0.21 ± 0.78 mg/dL, p = 0.028). In subgroup analyses stratified by body mass index and waist circumference, significant different SUA changes between FDR and non-FDR subjects were only found in obese (0.48 ± 0.87 mg/dL vs − 0.70 ± 0.71 mg/dL, p = 0.001) and centrally obese (0.59 ± 0.83 mg/dL vs − 0.55 ± 0.82 mg/dL, p = 0.011) subgroups. In multivariate analysis, visceral adiposity seemed mediating the different response in SUA metabolism between FDR and non-FDR subjects induced by short-term obesogenic diet.

A218 ASSOCIATIONS BETWEEN ADHERENCE TO LITERATURE-DERIVED DIETARY INDICES AND PRE-DISEASE BIOMARKERS: IMPLICATIONS FOR CROHN’S DISEASE PREVENTION

Abstract Background The incidence of Crohn’s disease (CD) is increasing globally, indicating a significant environmental influence such as diet. A plethora of dietary adherence (DA) patterns exist in the literature: the Mediterranean Diet (MD), Empirical Dietary Inflammatory Pattern (EDIP), Specific Carbohydrate Diet (SCD), and low Fermentable Oligosaccharide, Disaccharide, Monosaccharide, or Polyol diet (FODMAP) are all potential candidates to maintain a reduced level of inflammation, improving gastrointestinal function. Contrary, the Westernized diet (WD) is generally reported as a diet promoting inflammation in humans. Purpose To determine if DA to literature-derived dietary indices in a cohort of first-degree relatives (FDRs) of CD patients can modulate pre-disease biomarkers. Method We used food frequency questionnaire (FFQ) data from 2,696 healthy FDR subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We rederived each of the following scores using our FFQ data, utilizing originally described methods for the MD, EDIP, SCD, low FODMAP, and WD to obtain DA. Each diet was correlated pairwise via Kendall’s Tau. We fit multivariable regression models to identify the association of DA (top quintile vs remaining) and: i) intestinal permeability using urinary fractional excretion of lactulose to mannitol ratio (LMR), LMR≥0.03 defined abnormal; ii) subclinical inflammation using fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA, FCP≥250µg/g defined inflammation; and iii) fecal microbiome richness and composition using 16S rRNA sequencing. Two-sided p<0.05 for primary and q<0.05 for secondary analysis defined significance. Result(s) There were positive correlations between the MD, SCD, and low FODMAP, these diets negatively correlated with the WD. The EDIP negatively correlated with the SCD and low FODMAP, did not correlate with the MD, and positively correlated with the WD. No diet was associated with abnormal LMR or FCP. Only the SCD was associated with increased microbial richness (q=0.03). All diets were associated with microbial genera: the MD (n=18 taxa, (2.0-7<q-values< 0.04), EDIP (n=9, [2.8-4-0.05]), SCD (n=13, [3.7-11-0.05]), low FODMAP (n=14, [1.3-7-0.05]), and WD (n=1, [0.03]). Conclusion(s) This study shows that literature-derived dietary indices correlate generally with each other, yet none were not associated with abnormal LMR or FCP. However, we found that diet can impact microbiome richness and composition. Thus, it is tempting to speculate that diet is a possible intervention capable of maintain microbiome homeostasis to reduce future risk of CD. Submitted on behalf of the CCC-GEM consortium. Funding Crohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III The Leona M. and Harry B. Helmsley Charitable Trust Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Disease Disclosure of Interest None Declared

Examining the clinical correlates of conduct disorder in youth with bipolar disorder

BackgroundConduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. Methods357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/− CD were compared on rates of psychopathology in relatives. ResultsSubjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LimitationsThe generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. ConclusionsGiven the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.

Endothelial dysfunction due to decreased nitric oxide bioavailability in dysglycaemic subjects and first-degree relatives of type 2 diabetic patients

Abstract Background/Introduction Oxidative stress plays an important role in the pathogenesis of type 2 diabetes mellitus. Purpose We aimed to investigate oxidative stress and nitrites/nitrates concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDR) of type 2 diabetic patients with normal oral glucose test (OGTT), 40 subjects with abnormal OGTT (dysglycaemic) and 20 subjects with normal OGTT without parental history of diabetes (normoglycaemic). Methods Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm (Microscan, Glycocheck), a marker of endothelial glycocalyx integrity, coronary flow reserve (CFR) in the distal left anterior descending coronary artery, left ventricular global longitudinal strain (GLS), malondialdehyde (MDA), protein carbonyls (PC) and nitrites/nitrates plasma levels were assessed at 0 and 120 min of a 2-hour OGTT. Insulin sensitivity was evaluated using Matsuda and insulin sensitivity index (ISI). Results In all subjects, there were no significant changes in MDA and PC at 120 min after OGTT (p&amp;gt;0.05). Compared with normoglycaemic subjects, in FDR and dysglycaemic subjects, nitrites/nitrates levels were significantly decreased at 120 min (−24% versus −30% versus −3%, respectively) with a parallel increase in PBR (+7% versus +10% versus −3%) and a reduction in CFR (−11% versus −14% versus −6%) and GLS (−4% versus −4% versus +0.1%) (p&amp;lt;0.05 for all comparisons). The percent reduction of nitrites/nitrates levels was associated with abnormal values of Matsuda and ISI, reversely related with the percent increase of PBR (r=−0.60, p=0.001) and positively related with the percent decrease of CFR (r=0.39, p=0.038) and GLS (r=0.48, p=0.008). Conclusion Insulin resistance determines acute endothelial responses during OGTT leading to reduced nitric oxide production with resultant coronary and myocardial dysfunction in FDR and dysglycaemic subjects. Funding Acknowledgement Type of funding sources: None.

Overexpression of TLR7 and TLR9 Occurs Before Onset Symptoms In First-Degree Relatives of Rheumatoid Arthritis Patients

Autoantibodies have a central role in the physiopathology of Rheumatoid Arthritis (RA). However, the responsible factors that trigger and perpetuate the autoantibodies production are unknown. Toll-like receptors (TLRs) have been considered as promotors of autoantibodies production to break down the immunotolerance in RA. Evaluate the expression levels of TLR7 and TLR9 as well as their correlation with autoantibodies in first-degree relatives (FDR) of RA patients (seropositive and seronegative to ACPA), respect to early RA (eRA) and chronic RA (cRA) patients. We selected 32 RA patients (16 as eRA and 16 as cRA) and 32 FDR of RA patients (16 seropositive and 16 seronegative to ACPA). Expression levels of TLR7 and TLR9 in whole blood samples from each group were measured by real-time PCR using total RNA extracted from each subject. Also, correlation analysis between TLRs expression and autoantibodies was performed. The expression of TLR7 and TLR9 was diminished in RA patients (p <0.01) but elevated in ACPA- FDR (p <0.0001) and ACPA+ FDR (p <0.05) with a positive correlation between them (r=0.749, p <0.000). Moreover, the expression levels of TLR7 correlate positively with ACPA levels in both seropositive ACPA+ FDR subjects (r=0.582, p=0.018) and eRA patients (r=0.593, p=0.020). Our results showed overexpression of TLR7 and TLR9 may occur in preclinical RA subjects. TLR7 overexpression correlated with ACPA levels' production, suggesting TLR7 may play a role in ACPA development.

Abstract P65: Arterial Stiffness Relationship With Periventricular and Deep White Matter Hyperintensities in a Middle-Aged Population

Introduction and hypothesis: Periventricular white matter (PVWM) is perfused by perforators originating from the proximal large caliber cerebral arteries with direct transmission of systemic hemodynamic changes as compared to the deep white matter (DWM) that is perfused by distal perforators with dampened transmission. We hypothesized that PVWM hyperintensities (PVWMH) are more strongly associated with the systemic vascular properties representing arterial stiffness (AS) due to vascular aging and hypertension compared to DWM hyperintensities (DWMH). Methods: Apparently healthy first degree relatives of subjects with coronary artery disease who had brain MRI as participants in GeneSTAR were selected. PVWMH and DWMH volumes were computed by an automated analysis software. Arterial stiffness indicators included peak systolic blood pressure during treadmill test, pulse pressure (PP), brachial artery (BA) diameter, carotid distensibility index, and diastolic dysfunction estimated by filling and systolic emptying rates (SER) on sestamibi cardiac scan. Statistical analysis was completed using unadjusted and age-adjusted linear regression models in the cohort that was divided into 4 quartiles based on age distribution (1 st : 29-43, 2 nd : 44-51, 3 rd : 52-59, 4 th : 60-74). Results: 782 participants were included (age 51.05±10.6 years, 58.4% female, 39% African American, PVWMH volume 1977.01±5195.81 ml and DWMH volume 625.93±1108.37 ml). In the unadjusted analysis, PVWMH showed association with PP in the 1 st and 3 rd age quartiles (p= 0.02 and 0.03, respectively) and SER in the 2 nd and 4 th age quartiles (p=0.04 and 0.03). This relationship remained significant in the adjusted analysis for SER (p=0.047, and 0.032, respectively) and in the 1 st age quartile for PP (P=0.02). DWMH relationship with BA diameter was significant in the 2 nd age quartile in the unadjusted and adjusted models (P=0.011, and 0.02, respectively). DWMH was also associated with ratio of cardiac filling/SER (P=0.039 and 0.047) in the 1 st age quartile. Conclusions: In this exploratory analysis, AS measures show different relationships to PVWMH and DWMH across age groups in middle-aged population suggesting a potential mechanistic role of AS in WMH pathology.

Influence of HLA on clinical and analytical features of pediatric celiac disease

BackgroundCeliac disease (CD) is triggered by gluten and related prolamines in genetically susceptible individuals. We aimed to investigate the influence of HLA-DQ genotypes in clinical, serological and histological features related to CD.MethodsA retrospective observational study was performed including 463 Spanish patients with biopsy-proven CD. Clinical, serological, histological and HLA-DQ genetic data were collected from each participant. The presence of a family history of CD was also considered. Bivariate (chi-square tests or the Fisher’s exact test) and multivariate (logistic regression after adjusting for age and sex) analyses were performed to assess the association between clinical and laboratory parameters with HLA-DQ.ResultsA predominance of females (62%), classical clinical presentation (86%) and positive anti-transglutaminase 2/endomysium antibodies (99%) was observed in our sample, with a mean age at onset of 2.6 ± 0.1 years. Five percent of our patients were first-degree relatives of subjects with CD, with HLA-DQ genetics showing increased homozygosity of HLA-DQ2.5 (p = 0.03) and HLA-DQ8 (p = 0.09). In the non-CD family history group, an association between delayed disease onset and HLA-DQ8 carriage was observed (p < 0.001), besides an influence of HLA-DQB1*02 gene dosage on clinical presentation and severity of histological damage (after adjusting for age and sex, p = 0.05 and p = 0.02, respectively) and a trend towards presence of specific antibodies (p = 0.09). These associations could not be evaluated properly in the group of patients with affected first-degree relatives due to the small sample size.ConclusionsHLA-DQ genotypic frequencies differ slightly between CD patients depending on their family history of CD. In patients lacking CD first-degree relatives, carriage of HLA-DQ2.5 with double dose of HLA-DQB1*02 seems to be associated with classical clinical presentation and more severe histological damage.

Carotid intima-media thickness among normoglycemia and normotension first-degree relatives of type 2 diabetes mellitus.

Introduction: Theoretically, first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) are predisposed to have earlier and more severe atherosclerosis than non-FDR due to hereditary insulin resistance. A previous study reported that atherosclerotic plaques were found in 45.2% of young adults FDR of T2DM, but the study did not include non-FDR as control group. The aim of this study was to compare subclinical atherosclerosis (carotid intima-media thickness, CIMT) between FDR of T2DM and non-FDR.Method: This was a cross-sectional study involving 16 FDR subjects and 16 age-sex matched non-FDR subjects, aged 19–40 years, with normal glucose tolerance and no hypertension. Collected data included demographic characteristic, anthropometric measurement (BMI and waist circumference), laboratory analysis (fasting blood glucose, HbA1c, lipid profile), and CIMT examination (using B-mode ultrasound).Results: The mean of CIMT in the FDR group was higher than that in the non-FDR group (0.44 mm vs 0.38 mm, p=0.005). After adjusting for waist circumference, BMI, low-density lipoprotein cholesterol, and triglyceride, CIMT maintained significant difference between FDR and non-FDR subjects. BMI and waist circumference showed moderate correlation with CIMT.Conclusion: CIMT in young adult FDR of T2DM is thicker than that in age-and sex-matched non-FDR population.

Anticyclic Citrullinated Peptide Antibodies 3.1 and Anti-CCP-IgA Are Associated with Increasing Age in Individuals Without Rheumatoid Arthritis.

We investigated the association of age and anticyclic citrullinated peptide antibodies (anti-CCP) in subjects without rheumatoid arthritis (RA). Serum was tested for anti-CCP3.1 (IgG/IgA) in 678 first-degree relatives (FDR) of patients with RA and 330 patients with osteoarthritis (OA). Individual isotypes (anti-CCP-IgA and anti-CCP-IgG) were also tested in all FDR. In FDR, increasing age was significantly associated with positivity for anti-CCP3.1 (per year, OR 1.03) and anti-CCP-IgA (per year, OR 1.05) but not anti-CCP-IgG. In FDR and OA subjects, anti-CCP3.1 prevalence was significantly increased after age 50 years. Increasing age in individuals without RA should be considered in the interpretation of anti-CCP3.1 positivity.

Brain Network Organization Correlates with Autistic Features in Preschoolers with Autism Spectrum Disorders and in Their Fathers: Preliminary Data from a DWI Analysis.

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders that is characterized by an altered brain connectivity organization. Autistic traits below the clinical threshold (i.e., the broad autism phenotype; BAP) are frequent among first-degree relatives of subjects with ASD; however, little is known regarding whether subthreshold behavioral manifestations of ASD mirror also at the neuroanatomical level in parents of ASD probands. To this aim, we applied advanced diffusion network analysis to MRI of 16 dyads consisting of a child with ASD and his father in order to investigate: (I) the correlation between structural network organization and autistic features in preschoolers with ASD (all males; age range 1.5–5.2 years); (II) the correlation between structural network organization and BAP features in the fathers of individuals with ASD (fath-ASD). Local network measures significantly correlated with autism severity in ASD children and with BAP traits in fath-ASD, while no significant association emerged when considering the global measures of brain connectivity. Notably, an overlap of some brain regions that are crucial for social functioning (cingulum, superior temporal gyrus, inferior temporal gyrus, middle frontal gyrus, frontal pole, and amygdala) in patients with ASD and fath-ASD was detected, suggesting an intergenerational transmission of these neural substrates. Overall, the results of this study may help in elucidating the neurostructural endophenotype of ASD, paving the way for bridging connections between underlying genetic and ASD symptomatology.

Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia.

Aim The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects. Materials and Methods 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp. Blood samples taken before and at the end of the clamp were used for the flow cytometry analysis of lymphocyte and monocyte populations and for the assessment of cytokine levels. Results At fasting conditions, FDR showed a higher CD4/CD8 ratio of peripheral lymphocytes, a higher percentage of Th17 lymphocytes, and a lower content of intermediate monocytes when compared to controls. The CD4/CD8 ratio correlated with fat mass, insulin, and HOMA-IR in the entire group of subjects. Hyperinsulinemia decreased a relative content of peripheral CD4+ and increased a relative content of CD8+ T lymphocytes, thus decreasing the CD4/CD8 ratio by 18-22% in both groups of subjects. In FDR but not in controls, the decrease of CD4+ T lymphocyte content was partially based on the decrease of TH2 and TH17 lymphocyte subpopulations. In control subjects but not in FDR, the number of intermediate monocytes has declined in response to hyperinsulinemia. Conclusion The alterations of the CD4/CD8 lymphocyte ratio, relative content of TH17 cells, and intermediate monocytes in FDR are features of genetic predisposition to T2DM and may play a role in pathogenesis of T2DM. Short-term hyperinsulinemia affected mostly the immune cell populations deregulated in FDR subjects, which suggests important interplay between immune system homeostasis and insulin levels.

Risk indicators for venous thrombosis in first-degree relatives of patients with recurrent venous thromboembolism in Chinese.

Having encountered several subjects with venous thromboembolism (VTE) in 1 family in which 1 proband has recurrent VTE (rVTE), we aimed to assess the risk of VTE in first-degree relatives, especially the children of individuals with rVTE, and to investigate the association of endothelial nitric oxide synthase (eNOS) G894T polymorphism between Chinese persons with rVTE and their offspring.We collected information about family histories and blood samples from 126 individuals with rVTE who had presented to our institute from 2003 to 2014, and 126 population-based controls and the first-degree relatives of subjects in these 2 groups. We tested blood samples for heritable thrombophilia and calculated odds ratios (ORs) and kappa coefficients.First-degree relatives of individuals with rVTE patients had a statistically significant risk of developing VTE (OR 2.62, 95% confidence interval [CI] 1.61–4.26, P < 0.001). For siblings, the OR was 2.72 (95% CI 1.56–4.73, P < .001). Moreover, for each year that the patient was older, the OR was 0.98 (95% CI 0.97–0.99, P = 0.03). One (11.2%) of the 9 individuals who had the same eNOS G894T polymorphism as their probands had a history of VTE, whereas none of the 17 relatives without the same polymorphism had developed VTE. The associations between patients and their children were statistically significant for VTE (kappa = 0.23, P < 0.001) and for eNOS G894T (kappa = 0.03, P = 0.04).In this case-controlled study, we demonstrated a higher risk of VTE among first-degree relatives of individuals with rVTE, especially in siblings of younger subjects with rVTE. We also found that eNOS G894T polymorphism may be a predictor of VTE in offspring of individuals with rVTE.

The effects of vitamin D supplementation on adiponectin level and insulin resistance in first-degree relatives of subjects with type 2 diabetes: a randomized double-blinded controlled trial.

BackgroundDespite the certain role of both vitamin D and adiponectin in the regulation of insulin sensitivity, the interaction between these two agents has remained uncertain.ObjectiveThe present study aimed to determine whether vitamin D is able to change plasma adiponectin and affect glucose homeostasis and insulin sensitivity in first-degree relatives of subjects with type 2 diabetes.MethodsThis randomized clinical trial was conducted at Clinic of Shahid Sadoughi Hospital in Yazd, Iran, from January 25, 2012 to December 25, 2014. In this randomized, double-blinded controlled trial, 64 first-degree relatives of type 2 diabetic patients were assigned randomly to receive either vitamin D supplement (50000 IU vitamin D tablet weekly) plus lifestyle change as the intervention group (n = 32) or placebo plus lifestyle change as the control group (n = 32) for twelve weeks (three months).ResultsFifty-three patients (28 in the intervention group and 25 in the control group) completed the study. Serum levels of vitamin D increased while insulin level and consequently insulin resistance (calculated by HOMA formula) significantly decreased in the case group (p-value <0.001 for all variables). Although the values of these three biomarkers showed a slight increase in control group, the changes were not statistically significant. The levels of the changes in other markers including adiponectin, Fasting Blood Sugar (FBS), triglyceride, and total cholesterol remained insignificant in both study groups after completing interventions compared with before interventions.ConclusionThis study showed that decreased insulin resistance is expected by administrating vitamin D supplement in first-degree relatives of the patients with diabetes mellitus.Trial RegistrationThe trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: 201105176430N1.FundingThe authors received no financial support for the research or publication of this article.

White matter diffusivity and microarchitecture among schizophrenia subjects and first-degree relatives

BackgroundImpairments in structural and functional connections are demonstrated in schizophrenia. Certain disconnectional patterns may be biomarkers of elevated risk for schizophrenia. Convergent examination of multiple diffusion parameters and cognitive performance better illustrates pathophysiological significance of such disconnectional patterns. MethodsDiffusion Tensor Imaging data on 39 early-course schizophrenia subjects, 21 adolescent/young adult first-degree relatives (FDR) of schizophrenia subjects and 29 healthy controls (HC) were examined for threshold-free clusters of fractional anisotropy (FA) and radial diffusivity (RD) differences correcting for multiple comparisons. Regression models examined the variance contributed by anisotropy differences, age and sex. Group-wise differences on sustained attention, verbal memory and executive functions were examined and correlated with diffusivity measures controlling for age and sex. ResultsSchizophrenia subjects showed significantly decreased FA and increased RD in the forceps minor and superior longitudinal fasciculus (SLF) compared to HC. FDR showed decreased forceps minor FA compared to HC, and decreased SLF RD compared to HC and schizophrenia subjects. Quantitative RD differences were 2–3 fold higher compared to FA. Besides, forceps minor RD was inversely correlated with sustained attention in schizophrenia. ConclusionsSchizophrenia and FDR subjects show different patterns of white matter diffusivity compared to HC. While forceps minor changes may be a disease marker, SLF changes may be risk markers. In addition, RD may be a more robust risk marker than FA.

Circulating Chemerin Levels are Increased in First-Degree Relatives of Type 2 Diabetic Patients

Chemerin is an important risk factor of insulin resistance and metabolic syndrome. The aim of this study was to explore the potential role of chemerin in the early stage of diabetes development. 63 control subjects without any family history of diabetes and with normal glucose tolerance (NGT) and 74 healthy, first-degree relatives (FDRs) of type 2 diabetic patients were recruited in the study. All subjects underwent a 75 g oral glucose tolerance (OGTT) test after having fasted overnight. Plasma glucose, insulin, total cholesterol, HDL cholesterol, triglycerides, chemerin, and adiponectin were measured. FDR subjects had higher BMI, WHR, waist, fasting plasma glucose, fasting insulin, TG, UA, HOMA-IR, LDL-C, and lower HDL- C levels than control subjects (p < 0.05). The FDRs group had significantly lower adiponectin levels while chemerin was higher. Plasma chemerin levels were independently correlated with HOMA-IR, FINS, TG, FPG, and adiponectin level. Multiple stepwise regression analysis showed that HOMA-IR and TG were independent risk factors that influenced circulating chemerin levels. These findings showed a significant increase of chemerin levels in FDR subjects which suggested that chemerin may be involved in the development and progression of insulin resistance.

The music of the genes

The music of the genes

Low Prevalence of Interleukin-6 Haplotypes Associated with a Decreased Risk of Type 2 Diabetes in Mexican Subjects with a Family History of Type 2 Diabetes

There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 -598G>A-572G>C-174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of -598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99-7.36; p = 0.050 OR, 30.08; 95% CI, 0.58-1,568.06; p = 0.092). IL-6 -598/-572/-174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

SAT0098 Seropositivity of anti-cyclic citrullinated peptide antibody is more prevalent in unaffected first-degree relatives with multicases families of rheumatoid arthritis

ObjectivesThis study elucidates the prevalence of seropositivity and determinants for rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-mutated citrullinated vimentin (anti-MCV) antibodies in unaffected first-degree relatives (FDRs) of rheumatoid...

Reducing the Risk of Developing Diabetes

Reducing the Risk of Developing Diabetes

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels

ObjectiveIt has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). MethodSerum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. ResultsThere was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06–11.52]ng/ml versus 10.50 [4.30–20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0μg/ml versus 20.66±8.12μg/ml, p<0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30–0.79]; p=0.004 and OR=0.74, CI [0.67–0.82]; p<0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. ConclusionsThe FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs’ increased risk of diabetes needs to be further elucidated.