Dataset Information

Transforming growth factor-beta1 and incident type 2 diabetes: results from the MONICA/KORA case-cohort study, 1984-2002.

ABSTRACT:

Objective

Subclinical inflammation leads to insulin resistance and beta-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-beta1 (TGF-beta1)-a central, mainly immunosuppressive, and anti-inflammatory cytokine-were associated with incident type 2 diabetes.

Research design and methods

We measured serum levels of TGF-beta1 from 460 individuals with and 1,474 individuals without incident type 2 diabetes in a prospective case-cohort study within the population-based MONICA (MONItoring of Trends and Determinants in CArdiovascular Disease)/KORA (Cooperative Health Research in the Region of Augsburg) cohort.

Results

Elevated TGF-beta1 concentrations were associated with higher, not lower, risk for type 2 diabetes (age-, sex-, and survey-adjusted hazard ratios [95% CI] for increasing TGF-beta1 tertiles: 1.0, 1.08 [0.83-1.42], and 1.41 [1.08-1.83]; P(for) (trend) = 0.012). Adjustment for BMI and metabolic and lifestyle factors had virtually no impact on the effect size.

Conclusions

Elevated serum concentrations of the cytokine TGF-beta1 indicate an increased risk for type 2 diabetes. TGF-beta1 may be upregulated to counterbalance metabolic and immunological disturbances preceding type 2 diabetes.

SUBMITTER: Herder C

PROVIDER: S-EPMC2752926 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Transforming growth factor-beta1 and incident type 2 diabetes: results from the MONICA/KORA case-cohort study, 1984-2002.

Herder Christian C Zierer Astrid A Koenig Wolfgang W Roden Michael M Meisinger Christa C Thorand Barbara B

Diabetes care 20090710 10

<h4>Objective</h4>Subclinical inflammation leads to insulin resistance and beta-cell dysfunction. This study aimed to assess whether levels of circulating transforming growth factor-beta1 (TGF-beta1)-a central, mainly immunosuppressive, and anti-inflammatory cytokine-were associated with incident type 2 diabetes.<h4>Research design and methods</h4>We measured serum levels of TGF-beta1 from 460 individuals with and 1,474 individuals without incident type 2 diabetes in a prospective case-cohort st ...[more]

PMID: 19592635

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Project description:BACKGROUND:Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to assess the relevance of biomarkers combined to pathway groups for the development of T2D and CHD in the same cohort. METHODS:Forty-seven serum biomarkers were measured in the MONICA/KORA case-cohort study using clinical chemistry assays and ultrasensitive molecular counting technology. The T2D (CHD) analyses included 689 (568) incident cases and 1850 (2004) non-cases from three population-based surveys. At baseline, the study participants were 35-74 years old. The median follow-up was 14 years. We computed Cox regression models for each biomarker, adjusted for age, sex, and survey. Additionally, we assigned the biomarkers to 19 etiological pathways based on information from literature. One age-, sex-, and survey-controlled average variable was built for each pathway. We used the R2PM coefficient of determination to assess the explained disease risk. RESULTS:The associations of many biomarkers, such as several cytokines or the iron marker soluble transferrin receptor (sTfR), were similar in strength for T2D and CHD, but we also observed important differences. Lipoprotein (a) (Lp(a)) and N-terminal pro B-type natriuretic peptide (NT-proBNP) even demonstrated opposite effect directions. All pathway variables together explained 49% of the T2D risk and 21% of the CHD risk. The insulin-like growth factor binding protein 2 (IGFBP-2, IGF/IGFBP system pathway) best explained the T2D risk (about 9% explained risk, independent of all other pathway variables). For CHD, the myocardial-injury- and lipid-related-pathways were most important and both explained about 4% of the CHD risk. CONCLUSIONS:The biomarker-derived pathway variables explained a higher proportion of the T2D risk compared to CHD. The ranking of the pathways differed between the two diseases, with the IGF/IGFBP-system-pathway being most strongly associated with T2D and the myocardial-injury- and lipid-related-pathways with CHD. Our results help to better understand the pathophysiology of the two diseases, with the ultimate goal of pointing out targets for lifestyle intervention and drug development to ideally prevent both T2D and CHD development.

Project description:Data from meta-analyses of genome-wide association studies provided evidence for an association of polymorphisms with body mass index (BMI), and gene expression results indicated a role of these variants in the hypothalamus. It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure.It was our aim to investigate the association of these genetic factors with BMI in a large homogenous population-based sample to explore the association of these polymorphisms with lifestyle factors related to nutritional intake or energy expenditure, and whether such lifestyle factors could be mediators of the detected single-nucleotide polymorphism (SNP)-association with BMI. It was a further aim to compare the proportion of BMI explained by genetic factors with the one explained by lifestyle factors.The association of seven polymorphisms in or near the genes NEGR1, TMEM18, MTCH2, FTO, MC4R, SH2B1 and KCTD15 was analyzed in 12,462 subjects from the population-based MONICA/KORA Augsburg study. Information on lifestyle factors was based on standardized questionnaires. For statistical analysis, regression-based models were used.The minor allele of polymorphism rs6548238 C>T (TMEM18) was associated with lower BMI (-0.418?kg?m(-2), P=1.22 × 10(-8)), and of polymorphisms rs9935401 G>A (FTO) and rs7498665 A>G (SH2B1) with increased BMI (0.290?kg?m(-2), P=2.85 × 10(-7) and 0.145?kg?m(-2), P=9.83 × 10(-3)). The other polymorphisms were not significantly associated. Lifestyle factors were correlated with BMI and explained 0.037% of the BMI variance as compared with 0.006% of explained variance by the associated genetic factors. The genetic variants associated with BMI were not significantly associated with lifestyle factors and there was no evidence of lifestyle factors mediating the SNP-BMI association.Our data first confirm the findings for TMEM18 with BMI in a single study on adults and also confirm the findings for FTO and SH2B1. There was no evidence for a direct SNP-lifestyle association.

Project description:ObjectiveTo examine the relationship between symptoms of insomnia and sleep duration and incident total (non-fatal plus fatal) strokes, non-fatal strokes, and fatal strokes in a large cohort of men and women from the general population in Germany.MethodsIn four population-based MONICA (monitoring trends and determinants in cardiovascular disease)/KORA (Cooperative Health Research in the Region of Augsburg) surveys conducted between 1984 and 2001, 17,604 men and women (aged 25 to 74 years) were asked about issues like sleep, health behavior, and medical history. In subsequent surveys and mortality follow-ups, incident stroke cases (cerebral hemorrhage, ischemic stroke, transient ischemic attack, unknown stroke type) were gathered prospectively until 2009. Sex-specific hazard ratios (HR) and their 95% confidence intervals (CI) were estimated using sequential Cox proportional hazards regression models.ResultsDuring a mean follow-up of 14 years, 917 strokes (710 non-fatal strokes and 207 fatal strokes) were observed. Trouble falling asleep and difficulty staying asleep were not significantly related to any incident stroke outcome in either sex in the multivariable models. Among men, the HR for the association between short (≤5 hours) and long (≥10 hours) daily sleep duration and total strokes were 1.44 (95% CI: 1.01-2.06) and 1.63 (95% CI: 1.16-2.29), after adjustment for basic confounding variables. As for non-fatal strokes and fatal strokes, in the analyses adjusted for age, survey, education, physical activity, alcohol consumption, smoking habits, body mass index, hypertension, diabetes, and dyslipidemia, the increased risks persisted, albeit somewhat attenuated, but no longer remained significant. Among women, in the multivariable analyses the quantity of sleep was also not related to any stroke outcome.ConclusionIn the present study, symptoms of insomnia and exceptional sleep duration were not significantly predictive of incident total strokes, non-fatal strokes, and fatal strokes in either sex.

Project description:OBJECTIVES:To test the effects of body weight maintenance, gain, and loss on health care utilisation in terms of outpatient visits to different kinds of physicians in the general adult population. METHODS:Self-reported utilisation data were collected within two population-based cohorts (baseline surveys: MONICA-S3 1994/95 and KORA-S4 1999/2001; follow-ups: KORA-F3 2004/05 and KORA-F4 2006/08) in the region of Augsburg, Germany, and were pooled for present purposes. N=5,147 adults (complete cases) aged 25 to 64 years at baseline participated. Number of visits to general practitioners (GPs), internists, and other specialists as well as the total number of physician visits at follow-up were compared across 10 groups defined by body mass index (BMI) category maintenance or change. Body weight and height were measured anthropometrically. Hierarchical generalized linear regression analyses with negative binomial distribution adjusted for sex, age, socioeconomic status (SES), survey, and the need factors incident diabetes and first cancer between baseline and follow-up were conducted. RESULTS:In fully adjusted models, compared to the group of participants that maintained normal weight from baseline to follow-up, the following groups had significantly higher GP utilisation rates: weight gain from normal weight (+36%), weight loss from preobesity (+39%), maintained preobesity (+34%), weight gain after preobesity (+43%), maintained moderate obesity (+48%), weight gain from moderate obesity (+107%), weight loss from severe obesity (+114%), and maintained severe obesity (+83%). Regarding internists, those maintaining moderate obesity reported +107% more visits; those with weight gain from moderate obesity reported +91%. The latter group also had +41% more consultations with other physicians. Across all physicians, mean number of visits were estimated at 7.8 per year for maintained normal weight, 9 for maintained preobesity, 11 for maintained moderate obesity, and 12 for maintained severe obesity. Among those with weight loss, the mean number of visits were 8.7, 10.6 and 10.8 for baseline preobesity, moderate obesity, and severe obesity, respectively. Finally, those with weight gain from normal weight and preobesity reported 9.4 and 9.3 visits, respectively, and those with baseline moderate and follow-up severe obesity reported 13.1 visits (the most overall). Women reported higher GP and other physician utilisation. While all utilisation rates increased with age, GP utilisation was lower in middle to high SES groups. CONCLUSION:Compared to maintained normal weight over a 7- to 10-year period, maintained overweight, weight gain and weight loss are associated with higher outpatient physician utilisation in adults, especially after baseline obesity. These effects only partly became insignificant after inclusion of incident diabetes or first cancer into the model. Future research should further elucidate the associations between weight development and health care utilisation by BMI status and the mechanisms underlying these associations.

Dataset Information

Transforming growth factor-beta1 and incident type 2 diabetes: results from the MONICA/KORA case-cohort study, 1984-2002.

Objective

Research design and methods

Results

Conclusions

Publications

Transforming growth factor-beta1 and incident type 2 diabetes: results from the MONICA/KORA case-cohort study, 1984-2002.

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