Additive effect of non-alcoholic fatty liver disease on the development of diabetes in individuals with metabolic syndrome

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Highlights

  • The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome.

  • The presence of NAFLD alone without MetS was also associated with increased risk of diabetes.

  • The coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS.

Abstract

Introduction

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome (MetS), with insulin resistance as the common pathophysiology. In a current longitudinal cohort study, we evaluated the separate and combined effects of MetS and NAFLD on incident diabetes risk.

Methods

Participants were categorized into four groups on the basis of the presence of NAFLD and MetS at baseline (i.e., with NAFLD, with MetS, with both, or without either). We compared the development of diabetes among these four groups.

Results

During the mean follow up of 4 years, 435 of the 7849 participants (5.5%) developed diabetes. The age, sex, and smoking-adjusted risk of incident diabetes was higher in the NAFLD only group (HR 1.51, 95% CI 1.14–1.99), MetS only group (HR 2.82, 95% CI 2.01–3.95), and both group (HR 5.45, 95% CI 4.32–6.82) compared with the group of neither. When compared with the NAFLD only group, the adjusted HR for incident diabetes was 1.87 (95% CI 1.29–2.72) in the MetS only group and 3.62 (95% CI 2.74–4.77) in both group. Among individuals with MetS, the presence of NAFLD showed a significant increase in risk of incident diabetes even after further adjustment for MetS components including fasting glucose, TG, BMI, systolic BP, and HDL-C (HR 1.53, 95% CI 1.09–2.16).

Conclusion

The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome. Our results suggest that the coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS.

Introduction

Metabolic syndrome (MetS) is a clustering of several atherogenic metabolic abnormalities that include central obesity, impaired glucose metabolism, dyslipidemia, and hypertension [1]. Insulin resistance is considered to play a fundamental role in MetS and leads to the most of the abnormalities observed in MetS [2], [3]. Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid deposition in hepatocytes and includes wide spectrum of liver damage from simple steatosis to steatohepatitis and advanced fibrosis [4]. Currently, NAFLD is considered as the hepatic manifestation of MetS, with insulin resistance as the main pathogenic mechanism [5], [6]. Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and is closely linked to cardiovascular disease [3], [7]. Diagnosing and treating MetS is important since individuals with MetS are at increased risk of developing type 2 diabetes and cardiovascular disease [1], [8]. Several studies have reported that NAFLD contribute to the development of type 2 diabetes and is associated with increased cardiovascular risk [9], [10], [11], [12].

MetS and NAFLD share a common pathophysiologic mechanism [2], [5]. Many individuals with MetS also have NAFLD [13]. Thus, the coexistence of NAFLD may have effect on the contribution of MetS to the development of diabetes. However, the additive role of NAFLD on the incident diabetes risk in individuals with MetS is uncertain. Also, accumulating evidence suggests that the association of NAFLD with insulin resistance is independent of obesity and other metabolic components [6]. However, the magnitude of diabetes risk in NAFLD patients without MetS or in MetS patients without NAFLD is unclear, given the paucity of data on the separate effects of MetS and NAFLD on the development of diabetes [14].

It is important to understand the role of metabolic syndrome and NAFLD on the development of diabetes. The current longitudinal cohort study evaluated the separate and combined effects of metabolic syndrome and NAFLD on incident diabetes risk.

Section snippets

Patients and methods

We used the same data sources and methods as our previous study [9]. These are described below, along with additional methodological details.

Results

Overall, the participants were relatively young and not obese, with a mean BMI of 23.6 ± 2.8 kg/m2. Mean age of participants was 44.6 years and 68.9% of the participants were men. MetS and NAFLD was present at baseline in 16.7% and 29.2% of the participants, respectively. There was a gender difference in the prevalence of metabolic syndrome and NAFLD with more men (21.3% and 38.9%, respectively) affected by those disorders than women (6.5% and 9.7%, respectively). While 64.6% of individuals with

Discussion

In this study, the presence of NAFLD further increased the risk of incident diabetes in individuals with MetS. The presence of MetS increases the risk for type 2 diabetes.[8] NAFLD is considered as the hepatic manifestation of MetS, with insulin resistance as the common pathophysiologic mechanism, which is why many individuals with MetS have NAFLD [5], [6], [13]. Presently, 64.6% of individuals with MetS had concurrent NAFLD and the risk of diabetes among subjects with MetS was exaggerated by

Conflict of interest

The authors declared that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Acknowledgements

This work was supported by a grant (SMX1161861) from the Samsung Biomedical Research Institute, Republic of Korea. This funding source played no role in the study design, collection, analysis, and interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. E.J.R is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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    Ji Cheol Bae and Soo Kyoung Kim contributed equally to this work as first authors.

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