Combined influence of nonalcoholic fatty liver and body size phenotypes on diabetes risk

Abstract

Background: We aimed to determine the association between nonalcoholic fatty liver disease (NAFLD) and diabetes risk among body size phenotypes which was based on cross-classification of body mass index (BMI) categories (normal or overweight/obesity) and metabolic status (metabolically health or metabolically at-risk).

Methods: We conducted a cross-sectional analysis using a cohort of 10,761 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography. Subjects were classified as metabolically at-risk by having any two of the following, consistent with the Adult Treatment Panel-III metabolic syndrome definition: (1) systolic/diastolic blood pressure ≥130/85 mmHg, (2) triglycerides ≥1.7 mmol/L, (3) fasting blood glucose ≥5.6 mmol/L, (4) HDL-cholesterol ≥1.0/1.3 mmol/L for men/women.

Results: Among participants without metabolically at-risk, multivariate-adjusted odds ratios (ORs) for diabetes from NAFLD compared with those without NAFLD in the normal-weight (BMI <23 kg/m(2)) and overweight/obese (BMI ≥23 kg/m(2)) group were 2.10 (1.85-3.93) and 1.85 (1.35-2.53), respectively. Among participants with metabolically at-risk, the significant association between NAFLD and diabetes was lost, regardless of obesity status. There were only 27.1% subjects with the presence of the three factors (overweight/obesity, NAFLD, and metabolically at-risk) occurring together, while the three factors occurring together was common (56.16%) in diabetic individuals. The multivariate-adjusted ORs for diabetes were 1.1 (0.61-1.98) for overweight/obesity, 2.23 (1.05-5.14) for NAFLD, and 8.04 (5.0-12.09) for metabolically at-risk. The OR for the presence of all the three factors occurring together was 23.22 (13.96-38.63).

Conclusions: NAFLD was associated with diabetes risk among participants without metabolically at-risk. The clustering of overweight/obesity, NAFLD, and metabolically at-risk is common in diabetic subjects and strikingly and markedly increases the diabetes risk.

Fig. 1

Venn Diagrams for concordance between obesity and nonalcoholic fatty liver disease (NAFLD) or between metabolically at-risk and NAFLD. Venn Diagram for a visual display of NAFLD and overweight/obesity based on BMI ≥23 kg/m² in the whole population (a); Venn Diagram for a visual display of NAFLD and metabolically at-risk in the whole population (b). Metabolic risk indicates metabolically at-risk. Metabolically at-risk was defined in the Definition section

Fig. 2

Venn diagram for a visual display of how the three factors (overweight/obesity, NAFLD, and metabolically at-risk) cluster together. Metabolic risk indicates metabolically at-risk. Overweight/obesity, NAFLD, and metabolically at-risk were defined in the definition Section

Fig. 3

Combined effect of the presence of NAFLD and body size phenotypes on diabetes risk. Combined effect of the presence of NAFLD and body size phenotypes on the frequency of diabetes (a); Combined effect of the presence of NAFLD and body size phenotypes on the odds of diabetes (b). Odds ratios (95 % confidence intervals) of diabetes for participants categorized by cross-classification of four body size phenotypes and either the presence or absence of NAFLD were adjusted for age, sex, and triglycerides/HDL cholesterol. MHNW metabolically healthy normal weight, MHO metabolically healthy overweight or obese, MANW metabolically at-risk normal weight, and MAO metabolically at-risk overweight or obese. Each of the four body size phenotypes was defined in the definition section