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Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis

Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis
Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis
OBJECTIVE Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.

RESEARCH DESIGN AND METHODS We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (n ≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.

RESULTS A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.22, 95% CI 1.84–2.60; I2 = 79.2%). Patients with more “severe” NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (n = 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54–5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy.

CONCLUSIONS NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
1935-5548
372-382
Mantovani, Alessandro
5a544c0e-d01f-425a-8583-92c74c5c1e73
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Bonora, Enzo
7b902b49-d6bf-4b8d-b062-7980439081b2
Targher, Giovanni
dcf6ed52-21bb-4da4-a456-9d4b29faba8f
Mantovani, Alessandro
5a544c0e-d01f-425a-8583-92c74c5c1e73
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Bonora, Enzo
7b902b49-d6bf-4b8d-b062-7980439081b2
Targher, Giovanni
dcf6ed52-21bb-4da4-a456-9d4b29faba8f

Mantovani, Alessandro, Byrne, Christopher D., Bonora, Enzo and Targher, Giovanni (2018) Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis. Diabetes Care, 41 (2), 372-382. (doi:10.2337/dc17-1902).

Record type: Article

Abstract

OBJECTIVE Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.

RESEARCH DESIGN AND METHODS We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (n ≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.

RESULTS A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.22, 95% CI 1.84–2.60; I2 = 79.2%). Patients with more “severe” NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (n = 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54–5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy.

CONCLUSIONS NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.

Text NAFLD_T2DM risk_revised_clean copy_R1 - Accepted Manuscript
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Text Table S1_NOS - Accepted Manuscript
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Text Figure 1_by country - Accepted Manuscript
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Text Figure 2_by FU - Accepted Manuscript
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Text Figure 3_by NAFLD severity - Accepted Manuscript
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Text Figure S1_flow chart - Accepted Manuscript
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Text Figure S2_by study design - Accepted Manuscript
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Text Figure S3_funnel - Accepted Manuscript
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More information

Accepted/In Press date: 6 November 2017
e-pub ahead of print date: 22 January 2018
Published date: 1 February 2018

Identifiers

Local EPrints ID: 415465
URI: https://eprints.soton.ac.uk/id/eprint/415465
ISSN: 1935-5548
PURE UUID: 7e3e1540-0fe4-4881-93c2-5aea0df55a96
ORCID for Christopher D. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 10 Nov 2017 17:30
Last modified: 06 Jun 2018 12:54

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Contributors

Author: Alessandro Mantovani
Author: Enzo Bonora
Author: Giovanni Targher

University divisions

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