Dataset Information

Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study.

ABSTRACT:

Objective

To evaluate whether there is a difference in the association between nonalcoholic fatty liver disease (NAFLD) and incident diabetes based on the presence of impaired fasting glucose.

Research design and methods

A total of 7,849 individuals (5,409 men and 2,440 women) without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into four groups by the presence of impaired fasting glucose and NAFLD at baseline. The association between NAFLD and incident diabetes was evaluated separately in groups with normal and impaired fasting glucose.

Results

For 4 years, the incidence of diabetes in the NAFLD group was 9.9% compared with 3.7% in the non-NAFLD group, with multivariable-adjusted hazard ratio of 1.33 (95% CI 1.07-1.66). However, this higher risk for diabetes only existed in the impaired fasting glucose group.

Conclusions

Our study suggests that NAFLD has an independent and additive effect on the development of diabetes under conditions of impaired insulin secretion.

SUBMITTER: Bae JC

PROVIDER: S-EPMC3041216 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study.

Bae Ji Cheol JC Rhee Eun Jung EJ Lee Won Young WY Park Se Eun SE Park Cheol Young CY Oh Ki Won KW Park Sung Woo SW Kim Sun Woo SW

Diabetes care 20110128 3

<h4>Objective</h4>To evaluate whether there is a difference in the association between nonalcoholic fatty liver disease (NAFLD) and incident diabetes based on the presence of impaired fasting glucose.<h4>Research design and methods</h4>A total of 7,849 individuals (5,409 men and 2,440 women) without diabetes, who underwent comprehensive health check-ups annually for 5 years, were categorized into four groups by the presence of impaired fasting glucose and NAFLD at baseline. The association betwe ...[more]

PMID: 21278140

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Project description:BACKGROUNDHepatic de novo lipogenesis (DNL) and β-oxidation are tightly coordinated, and their dysregulation is thought to contribute to the pathogenesis of nonalcoholic fatty liver (NAFL). Fasting normally relaxes DNL-mediated inhibition of hepatic β-oxidation, dramatically increasing ketogenesis and decreasing reliance on the TCA cycle. Thus, we tested whether aberrant oxidative metabolism in fasting NAFL subjects is related to the inability to halt fasting DNL.METHODSForty consecutive nondiabetic individuals with and without a history of NAFL were recruited for this observational study. After phenotyping, subjects fasted for 24 hours, and hepatic metabolism was interrogated using a combination of 2H2O and 13C tracers, magnetic resonance spectroscopy, and high-resolution mass spectrometry.RESULTSWithin a subset of subjects, DNL was detectable after a 24-hour fast and was more prominent in those with NAFL, though it was poorly correlated with steatosis. However, fasting DNL negatively correlated with hepatic β-oxidation and ketogenesis and positively correlated with citrate synthesis. Subjects with NAFL but undetectable fasting DNL (25th percentile) were comparatively normal. However, those with the highest fasting DNL (75th percentile) were intransigent to the effects of fasting on the concentration of insulin, non-esterified fatty acid, and ketones. Additionally, they sustained glycogenolysis and were spared the loss of oxaloacetate to gluconeogenesis in favor of citrate synthesis, which correlated with DNL and diminished ketogenesis.CONCLUSIONMetabolic flux analysis in fasted subjects indicates that shared metabolic mechanisms link the dysregulations of hepatic DNL, ketogenesis, and the TCA cycle in NAFL.TRIAL REGISTRATIONData were obtained during the enrollment/non-intervention phase of Effect of Vitamin E on Non-Alcoholic Fatty Liver Disease, ClinicalTrials.gov NCT02690792.FUNDINGThis work was supported by the University of Texas Southwestern NORC Quantitative Metabolism Core (NIH P30DK127984), the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (R01DK078184, R01DK128168, R01DK087977, R01DK132254, and K01DK133630), the NIH/National Institute on Alcohol Abuse and Alcoholism (K01AA030327), and the Robert A. Welch Foundation (I-1804).

Dataset Information

Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study.

Objective

Research design and methods

Results

Conclusions

Publications

Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study.

Similar Datasets

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