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Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.

ABSTRACT: AIMS/HYPOTHESIS:Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals. METHODS:We studied two prospective cohorts: the Framingham Offspring Study (n?=?2,023) and the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study (n?=?887) cohorts. Insulin resistance was estimated by HOMA-insulin resistance (HOMA-IR). We used logistic regression analysis to test the association between adiponectin and incident type 2 diabetes overall and in insulin-resistant vs insulin-sensitive individuals (defined by ? vs <75th percentile of HOMA-IR). RESULTS:At baseline, Framingham's participants were 60?±?9 years old and 56% were women; KORA's participants were 63?±?5 years old and 49% were women. Type 2 diabetes incidence was 5.4% over 6.5 years (n?=?109) in Framingham and 10.5% over 8 years (n?=?93) in KORA. Lower adiponectin levels were associated with type 2 diabetes incidence in both cohorts. In insulin-resistant individuals, lower adiponectin levels were associated with higher risk of type 2 diabetes incidence (OR 1.60 [95% CI 1.10-2.31] per SD decrease in Framingham, p?=?0.01; and OR 2.34 [95% CI 1.16-4.73] in KORA, p?=?0.02); while this was not observed in insulin-sensitive individuals (OR 1.10 [95% CI 0.73-1.67] in Framingham, p?=?0.64; and OR 1.34 [95%CI: 0.88-2.03] in KORA, p?=?0.18). CONCLUSIONS/INTERPRETATION:We conclude that lower adiponectin levels are associated with higher risk of type 2 diabetes in insulin-resistant but not in insulin-sensitive individuals. This suggests that some level of insulin resistance is needed to see deleterious effects of low adiponectin.

SUBMITTER: Hivert MF

PROVIDER: S-EPMC3223124 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.

Hivert M-F MF Sullivan L M LM Shrader P P Fox C S CS Nathan D M DM D'Agostino R B RB Wilson P W F PW Kowall B B Herder C C Meisinger C C Thorand B B Rathmann W W Meigs J B JB

Diabetologia 20110219 5

<h4>Aims/hypothesis</h4>Lower adiponectin levels are associated with higher risk of incident type 2 diabetes. Most analyses have been adjusted for confounding factors, but few have taken into account insulin resistance per se. We tested the hypothesis that the association of adiponectin levels with incident type 2 diabetes differs between insulin-resistant and insulin-sensitive individuals.<h4>Methods</h4>We studied two prospective cohorts: the Framingham Offspring Study (n = 2,023) and the Coop ...[more]

PMID: 21336532

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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.

Project description:BackgroundDue to the asymptomatic nature of the early stages, chronic kidney disease (CKD) is usually diagnosed at late stages and lacks targeted therapy, highlighting the need for new biomarkers to better understand its pathophysiology and to be used for early diagnosis and therapeutic targets. Given the close relationship between CKD and cardiovascular disease (CVD), we investigated the associations of 233 CVD- and inflammation-related plasma proteins with kidney function decline and aimed to assess whether the observed associations are causal.MethodsWe included 1140 participants, aged 55-74 years at baseline, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort study, with a median follow-up time of 13.4 years and 2 follow-up visits. We measured 233 plasma proteins using a proximity extension assay at baseline. In the discovery analysis, linear regression models were used to estimate the associations of 233 proteins with the annual rate of change in creatinine-based estimated glomerular filtration rate (eGFRcr). We further investigated the association of eGFRcr-associated proteins with the annual rate of change in cystatin C-based eGFR (eGFRcys) and eGFRcr-based incident CKD. Two-sample Mendelian randomization was used to infer causality.ResultsIn the fully adjusted model, 66 out of 233 proteins were inversely associated with the annual rate of change in eGFRcr, indicating that higher baseline protein levels were associated with faster eGFRcr decline. Among these 66 proteins, 21 proteins were associated with both the annual rate of change in eGFRcys and incident CKD. Mendelian randomization analyses on these 21 proteins suggest a potential causal association of higher tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) level with eGFR decline.ConclusionsWe reported 21 proteins associated with kidney function decline and incident CKD and provided preliminary evidence suggesting a potential causal association between TNFRSF11A and kidney function decline. Further Mendelian randomization studies are needed to establish a conclusive causal association.

Dataset Information

Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.

Publications

Insulin resistance influences the association of adiponectin levels with diabetes incidence in two population-based cohorts: the Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 study and the Framingham Offspring Study.

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