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C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus.

ABSTRACT: BACKGROUND/AIM:C-Reactive protein (CRP) is a common marker of inflammation. Elevated CRP levels have been associated with increased risk of development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association of CRP gene polymorphisms with early-onset T2DM and the effect of genetic variants on CRP level. MATERIALS AND METHODS:In total, 948 individuals with early-onset (n=271) or late-onset (n=677) T2DM were enrolled in the study. Five single-nucleotide polymorphisms (SNPs) in the CRP gene, namely rs3093077, rs2808630, rs1800947, rs11265263, and rs11265265, were selected for genotyping, and CRP levels were measured. RESULTS:Genotypic, allelic, and haplotype frequencies of these five SNPs were not significantly different between patients with early- and those with late-onset. T2DM Higher serum CRP levels were independently associated with the C-allele of rs3093077 and T-allele of rs11265265 (p<0.001). Furthermore, the C-allele of rs3093077 was associated with higher CRP level in both early- (p=0.016) and late-onset (p<0.001) T2DM. CONCLUSION:CRP gene variants may contribute to the risk of early-onset T2DM by affecting the serum CRP level.

SUBMITTER: Huang YC

PROVIDER: S-EPMC6754999 | biostudies-literature | 2019 Sep-Oct

REPOSITORIES: biostudies-literature

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C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus.

Huang Yu-Chuen YC Chen Ching-Chu CC Wang Tzu-Yuan TY Nguyen Hung Tran The HTT Chen Yung-Hsiang YH Wu Chia-Ming CM Chang Ya-Wen YW Liao Wen-Ling WL Tsai Fuu-Jen FJ

In vivo (Athens, Greece) 20190901 5

<h4>Background/aim</h4>C-Reactive protein (CRP) is a common marker of inflammation. Elevated CRP levels have been associated with increased risk of development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association of CRP gene polymorphisms with early-onset T2DM and the effect of genetic variants on CRP level.<h4>Materials and methods</h4>In total, 948 individuals with early-onset (n=271) or late-onset (n=677) T2DM were enrolled in the study. Five single-nucleotide poly ...[more]

PMID: 31471424

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Project description:BackgroundAlthough cumulating evidence has suggested that early-onset type 2 diabetes mellitus (T2DM) conferred on patients a broader tendency for complications beyond vascular ones, a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.MethodWe prospectively studied 1 777 early-onset (age at diagnosis ≤ 45 years) and 35 889 late-onset (>45 years) T2DM patients with matched unexposed individuals from the UK Biobank. Diabetes-specific and -related complications were examined using phenome-wide association analysis, with patterns identified by comorbidity network analysis. We also evaluated the effect of lifestyle modifications and glycemic control on complication development.ResultsThe median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years, respectively. Compared to late-onset T2DM patients, patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs [hazard ratio (HR) 3.46 vs. 1.72], the endocrine/metabolic system (HR 3.08 vs. 2.01), and the neurological system (HR 2.70 vs. 1.81). Despite large similarities in comorbidity patterns, a more complex and well-connected network was observed for early-onset T2DM. Furthermore, while patients with early-onset T2DM got fewer benefits (12.67% reduction in pooled HR for all studied complications) through fair glycemic control (median HbA1c ≤ 53 mmol/mol) compared to late-onset T2DM patients (18.01% reduction), they seemed to benefit more from favorable lifestyles, including weight control, healthy diet, and adequate physical activity.ConclusionsOur analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM. Aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM-related complications.

Project description:The type 2 deiodinase gene (DIO2) encodes a deiodinase that converts the thyroid prohormone, thyroxine, to the biologically active triiodothyronine. Thyroid hormones regulate energy balance and may also influence glucose metabolism. Therefore, we hypothesized that variations in DIO2 could contribute to obesity or type 2 diabetes mellitus (T2DM) in Pima Indians.Sequencing of the DIO2 gene in DNA from 83 Pima Indians identified 12 single-nucleotide polymorphisms (SNPs). Several of these SNPs were in perfect genotypic concordance among the 83 samples that were sequenced, and all 12 could be divided into five linkage disequilibrium groups. One representative SNP from each group (Thr92Ala, rs225011, rs225015, rs6574549, and a rare 5' flanking SNP) was selected for further genotyping for association analyses. In this study, the five selected variants in DIO2, as described above, were genotyped in three groups of Pima Indians: (i) a case (n=150)/control (n=150) group for early-onset T2DM (onset age <25 years); (ii) a case (n=362)/control (n=127) group for obesity; (iii) a large (n=1,311, cases n=810/controls n=501) family-based group, of which 256 nondiabetic subjects had undergone detailed metabolic phenotyping.The Thr92Ala variant common in Pima Indians, rs225011, and rs225015 were modestly associated with early-onset T2DM (p=0.01-0.04) in the case-control study, but were not associated with obesity in the obesity case-control study, nor associated with T2DM (at any age) or body-mass index (BMI; as a quantitative trait) in the family-based analysis. Thr92Ala, rs225011, rs225015, and rs6574549 were also nominally associated with hepatic glucose output (p=0.02). rs6574549 was associated with fasting insulin (p=0.02), insulin action (p=0.04), and energy expenditure (p=0.02). None of these nominal associations remained statistically significant after corrections for multiple testing.We propose that variation in DIO2 may have a subtle role in altering metabolic processes that lead to early-onset T2DM, but this gene does not have a large impact on T2DM at older ages, nor does DIO2 influence BMI in the Pima Indian population.

Project description:BACKGROUND: Apelin is an adipokine that plays a role in the regulation of glucose homeostasis and in obesity. The relationship between apelin serum concentration and dysmetabolic conditions such as type 2 diabetes (T2D) is still controversial. Aims of our study are: 1) determine the circulating levels of apelin in a large cohort of Italian subjects with T2D, T1D and in non-diabetic controls; 2) identify putative metabolic determinants of modified apelin concentrations, in order to search possible mechanism of apelin control; 3) investigate changes in apelin levels in response to sharp modifications of glucose/insulin metabolism in T2D obese subjects before and 3 days after bariatric surgery. METHODS: We recruited 369 subjects, 119 with T2D, 113 with T1D and 137 non-diabetic controls. All subjects underwent a complete clinical examination, including anthropometric and laboratory measurements. Serum apelin levels were determined by EIA (immunoenzyme assay). RESULTS: Patients with T2D had significantly higher serum apelin levels compared to controls (1.23 ± 1.1 ng/mL vs 0.91 ± 0.7 ng/mL, P<0.001) and to T1D subjects (0.73 ± 0.39 ng/mL, P<0.001). Controls and T1D subjects did not differ significantly in apelin levels. Apelin concentrations were directly associated with fasting blood glucose (FBG), body mass index (BMI), basal Disposition Index (DI-0), age, and diagnosis of T2D at bivariate correlation analysis. Multiple regression analysis confirmed that diagnosis of T2D, basal DI-0 and FBG were all determinants of serum apelin levels independently from age and BMI. Bariatric surgery performed in a subgroup of obese diabetic subjects (n = 12) resulted in a significant reduction of apelin concentrations compared to baseline levels (P = 0.01). CONCLUSIONS: Our study demonstrates that T2D, but not T1D, is associated with increased serum apelin levels compared to non-diabetic subjects. This association is dependent on impaired glucose homeostasis, and disappears after bariatric surgery, providing further evidence regarding the relationship between apelin and the regulation of glucose metabolism.

Project description:BackgroundGlucose metabolism links closely to cholesterol metabolism. Posttransplant diabetes mellitus (PTDM) adversely affects posttransplant outcomes, but its risk factors in relation to cholesterol metabolism have not been fully delineated. The apolipoprotein B/A1 (Apo B/A1) ratio, which is associated with insulin resistance, has not been evaluated in kidney transplant recipients as a risk factor for PTDM.ObjectiveThe objective of this study was to determine whether serum apolipoprotein profiles predict late PTDM, defined as a new onset diabetes occurring greater than 3 months posttransplant.DesignRetrospective chart review of a prevalent population of kidney transplant recipients.SettingLarge transplant center in Ontario, Canada.PatientsWe identified 1104 previously nondiabetic adults who received a kidney transplant between January 1, 1998, and December 1, 2015, and were followed at 1 transplant center.MeasurementsRecipients provided testing for serum apolipoprotein B (Apo B) and apolipoprotein A1 (Apo A1) concentrations from 2010, either at 3 months posttransplant for new transplant recipients or the next clinic visit for prevalent recipients. Late PTDM defined using Canadian Diabetes Association criteria as occurring ≥3 months posttransplant was recorded until May 1, 2016.MethodsAll analyses were conducted with R, version 3.4.0 (The R Foundation for Statistical Computing). Comparisons were made using Student t test, Fisher exact test or chi-square test, Kaplan-Meier methodology with the logrank test, or Cox proportional hazards analysis as appropriate. Covariates for the multivariate Cox proportional hazards models of PTDM as the outcome variable were selected based on significance of the univariate associations and biological plausibility.ResultsThere were 53 incident late PTDM cases, or 1.71 cases per 100 patient-years. Incident late PTDM differed between the highest and lowest quartiles for Apo B/A1 ratio, 2.47 per 100 patient-years vs 0.88 per 100 patient-years (P = .005 for difference). In multiple Cox regression analysis, first measured serum Apo B/A1 concentration better predicted subsequent PTDM than low-density lipoprotein cholesterol (LDL-C; hazard ratio [HR] = 7.80 per unit increase, P = .039 vs HR = 1.05 per unit increase, P = .774). Non-high-density lipoprotein cholesterol (HDL-C) concentrations also did not predict PTDM (P = .136). By contrast to Apo B, Apo A1 was protective against PTDM in statin users (HR = 0.17 per unit increase, P = .016).LimitationsPosttransplant diabetes mellitus cases occurring before apolipoprotein testing was implemented were not included in the analysis.ConclusionsApolipoproteins B and A1 better predict late PTDM than conventional markers of cholesterol metabolism.

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C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus.

Publications

C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus.

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