The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease - PubMed (original) (raw)

. 2022 Jul;28(3):565-574.

doi: 10.3350/cmh.2022.0096. Epub 2022 May 19.

Kai En Chan 1, Yip Han Chin 1, Rebecca Wenling Zeng 1, Pei Chen Tsai 1, Wen Hui Lim 1, Darren Jun Hao Tan 1, Chin Meng Khoo 2, Lay Hoon Goh 3 4, Zheng Jye Ling 4 5, Anand Kulkarni 6, Lung-Yi Loey Mak 7, Daniel Q Huang 1 8 9, Mark Chan 10, Nicholas Ws Chew 1 10, Mohammad Shadab Siddiqui 11, Arun J Sanyal 12, Mark Muthiah 1 8 9

Affiliations

The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease

Cheng Han Ng et al. Clin Mol Hepatol. 2022 Jul.

Abstract

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.

Methods: Data from the National Health and Nutrition Examination Survey 1999-2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.

Results: Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.

Conclusion: Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

Keywords: Diabetes mellitus; Non-alcoholic fatty liver Disease; Prediabetic state.

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Conflict of interest statement

Conflicts of Interest

AJS is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect and Galmed. He has served as a consultant to Astra Zeneca, Nitto Denko, Enyo, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, Merck, Valeant, Boehringer-Ingelheim, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Affimune, Chemomab, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen and Bristol Myers Squibb. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, Astra Zeneca, Malinckrodt, Cumberland and Norvatis. He receives royalties from Elsevier and UptoDate. MN has been on the advisory board for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Siemens and Roche diagnostic; MN has received research support from Allergan, BMS, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Pfizer, Shire, Viking and Zydus; MN is a minor shareholder or has stocks in Anaetos, Rivus Pharma and Viking.

Figures

Figure 1.

Figure 1.

Proportion of nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, and stroke.

Figure 2.

Figure 2.

Non-invasive measures of fibrosis in non-diabetic, prediabetic and diabetic nonalcoholic fatty liver disease (NAFLD). APRI, Aspartate Aminotransferase to Platelet Ratio Index; FIB-4, fibrosis-4.

Figure 3.

Figure 3.

Forest plot of outcomes in non-diabetic, pre-diabetic, and diabetic nonalcoholic fatty liver disease.

Figure 4.

Figure 4.

(A) Overall mortality in non-diabetic, prediabetic, and diabetic nonalcoholic fatty liver disease (NAFLD). (B) Cardiovascular mortality in non-diabetic, prediabetic and diabetic NAFLD.

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