Dataset Information

Plasma metabolomic signatures of obesity and risk of type 2 diabetes.

ABSTRACT:

Objective

The mechanisms linking obesity to type 2 diabetes (T2D) are not fully understood. This study aimed to identify obesity-related metabolomic signatures (MESs) and evaluated their relationships with incident T2D.

Methods

In a nested case-control study of 2076 Chinese adults, 140 plasma metabolites were measured at baseline, linear regression was applied with the least absolute shrinkage and selection operator to identify MESs for BMI and waist circumference (WC), and conditional logistic regression was applied to examine their associations with T2D risk.

Results

A total of 32 metabolites associated with BMI or WC were identified and validated, among which 14 showed positive associations and 3 showed inverse associations with T2D; 8 and 18 metabolites were selected to build MESs for BMI and WC, respectively. Both MESs showed strong linear associations with T2D: odds ratio (95% CI) comparing extreme quartiles was 4.26 (2.00-9.06) for BMI MES and 9.60 (4.22-21.88) for WC MES (both p-trend < 0.001). The MES-T2D associations were particularly evident among individuals with normal WC: odds ratio (95% CI) reached 6.41 (4.11-9.98) for BMI MES and 10.38 (6.36-16.94) for WC MES. Adding MESs to traditional risk factors and plasma glucose improved C statistics from 0.79 to 0.83 (p < 0.001).

Conclusions

Multiple obesity-related metabolites and MESs strongly associated with T2D in Chinese adults were identified.

SUBMITTER: Pan XF

PROVIDER: S-EPMC9633360 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Plasma metabolomic signatures of obesity and risk of type 2 diabetes.

Pan Xiong-Fei XF Chen Zsu-Zsu ZZ Wang Thomas J TJ Shu Xiang X Cai Hui H Cai Qiuyin Q Clish Clary B CB Shi Xu X Zheng Wei W Gerszten Robert E RE Shu Xiao-Ou XO Yu Danxia D

Obesity (Silver Spring, Md.) 20220925 11

<h4>Objective</h4>The mechanisms linking obesity to type 2 diabetes (T2D) are not fully understood. This study aimed to identify obesity-related metabolomic signatures (MESs) and evaluated their relationships with incident T2D.<h4>Methods</h4>In a nested case-control study of 2076 Chinese adults, 140 plasma metabolites were measured at baseline, linear regression was applied with the least absolute shrinkage and selection operator to identify MESs for BMI and waist circumference (WC), and condit ...[more]

PMID: 36161775

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Project description:Background/objectivePlasma apoB predicts the incidence of type 2 diabetes (T2D); however, the link between apoB-linpoproteins and risks for T2D remain unclear. Insulin resistance (IR) and compensatory hyperinsulinemia characterize prediabetes, and the involvement of an activated interleukin-1 (IL-1) family, mainly IL-1β and its receptor antagonist (IL-Ra), is well documented. ApoB-lipoproteins were reported to promote IL-1β secretion in immune cells; however, in vivo evidence is lacking. We hypothesized that obese subjects with hyperapoB have an activated IL-1 system that explains hyperinsulinemia and IR in these subjects.Subjects/methodsWe examined 81 well-characterized normoglycemic men and postmenopausal women (⩾27 kg m(-2), 45-74 years, non-smokers, sedentary, free of chronic disease). Insulin secretion and sensitivity were measured by the gold-standard Botnia clamp, which is a combination of a 1-h intravenous glucose tolerance test (IVGTT) followed by 3-h hyperinsulinemic euglycemic clamp.ResultsPlasma IL-1β was near detection limit (0.071-0.216 pg ml(-1)), while IL-1Ra accumulated at 1000-folds higher (77-1068 pg ml(-1)). Plasma apoB (0.34-1.80 g l(-1)) associated significantly with hypersinsulinemia (totalIVGTT: C-peptide r=0.27, insulin r=0.22), IR (M/I=-0.29) and plasma IL-1Ra (r=0.26) but not with IL-1β. Plasma IL-1Ra associated with plasma IL-1β (r=0.40), and more strongly with hyperinsulinemia and IR than apoB, while the association of plasma IL-1β was limited to second phase and total insulin secretion (r=0.23). Adjusting the association of plasma apoB to hyperinsulinemia and IR for IL-1Ra eliminated these associations. Furthermore, despite equivalent body composition, subjects with hyperapoB (⩾80th percentile, 1.14 g l(-1)) had higher C-peptide secretion and lower insulin sensitivity than those with low plasma apoB (⩽20th percentile, 0.78 g l(-1)). Adjustment for plasma IL-1 Ra eliminated all group differences.ConclusionPlasma apoB is associated with hyperinsulinemia and IR in normoglycemic obese subjects, which is eliminated upon adjustment for plasma IL-1Ra. This may implicate the IL-1 family in elevated risks for T2D in obese subjects with hyperapoB.

Dataset Information

Plasma metabolomic signatures of obesity and risk of type 2 diabetes.

Objective

Methods

Results

Conclusions

Publications

Plasma metabolomic signatures of obesity and risk of type 2 diabetes.

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