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

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.Conclusions: 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.

Depression in non-alcoholic fatty liver disease is associated with an increased risk of complications and mortality

“…concomitant diabetes and obesity commonly associated with NAFLD can intensify the state of inflammation and oxidative stress resulting in a higher risk of depression (34)(35)(36).…”

“…The serotonin pathway can be affected in this group of patients as the expression of monoamine oxidase-A, one of the enzymes catalyzing monoamines like serotonin, has been shown to be increased in NASH ( 33 ). Moreover, the compounded presence of concomitant diabetes and obesity commonly associated with NAFLD can intensify the state of inflammation and oxidative stress resulting in a higher risk of depression ( 34 – 36 ).…”

“…Firstly, diagnosis of hepatic steatosis was limited to FLI and US-FLI as imaging-based diagnosis was unavailable for the NHANES 2000–2018 dataset. Still, the FLI has been widely employed and validated ( 62 ) in population-based studies for liver steatosis ( 36 , 63 , 64 ). In addition, the use of antidepressants for a diagnosis of depression in a proportion of the population could result in the presence of a string bias in the evaluation of the results.…”

Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality

“…The increased fat deposition in hepatocytes results from a myriad of factors including insulin resistance, lipotoxicity, and changes in gut microbiota can increase hepatic and extrahepatic complications (7)(8)(9). Several epidemiological studies have shown that NAFLD can lead to an increment in all-cause mortality and is significantly associated with the development of hypertension (HTN), cardiovascular diseases (CVDs), hepatocellular carcinoma, diabetes mellitus, and renal and lung diseases (6,(10)(11)(12)(13)(14)(15). Hypertension (HTN) accounted for 8.5 million deaths in 2015 alone (16,17) and is a known risk factor associated with NAFLD (13,18).…”

Non-alcoholic fatty liver disease and risk of dementia: Unmet need for a pooled analysis of cohort studies

“…The heterogeneity in the study population may include not only sociodemographic characteristics, such as age, sex, ethnicity, and household income but also underlying comorbidities, such as prediabetes and diabetes. [7] In addition, consideration of a history of diseases that are considered to be associated with incident dementia in inclusion criteria for the study population may be important to better define the independent association of NAFLD with dementia. Therefore, consideration of the heterogeneity of the study population in great detail may better define the association of NAFLD with potential complications in future pooled analyses.…”