However, few studies have been conducted on the risk of diabetes in subjects with prediabetes in the presence of NAFLD. In this study, we investigated the association of NAFLD with diabetes and the impact of WC and BMI changes in subjects with prediabetes. By definition, it is important to rule out excessive alcohol consumption for the diagnosis of NAFLD.
The overall worldwide prevalence of NAFLD in the general adult population is 25% as the most prevalent liver disease8). Estimates of the worldwide prevalence of NAFLD range from 6.3 to 33%, with an average of 20% in the general population, based on a variety of estimation methods 4). The clinical implications of NAFLD are considered to be common in the general population and the potential to progress to NASH, liver cirrhosis and hepatic failure2).
The presence of NAFLD had an additive effect on future risk of T2DM among subjects with impaired fasting glucose (IFG) 14). The prevalence of NAFLD increases by a factor of 4.6 in obese people, defined as those with a body mass index (BMI) of at least 30 kg/m2 19). Thus, whether the dynamic change of WC plays an important role in the development of diabetes and/or the association of NAFLD is not well documented.
In light of these findings, we designed our current study to investigate the association of NAFLD with diabetes and the impact of WC and BMI changes in a prediabetic, middle-aged, Korean adult.
Subjects and Methods
- Study population
- Clinical and laboratory measurements
- Definitions of Diabetes, Prediabetes and Nonalcoholic Fatty liver disease (NAFLD) Subjects with diabetes were defined as those with a fasting plasma glucose (FPG) level
- Statistical Analysis
Waist circumference (WC) (in cm) was measured midway between the costal margin and the iliac crest at the end of a normal expiration. BP was measured on the right arm after 5 minutes of rest using an automatic manometer with an appropriate cuff size. Fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured using the enzymatic colorimetric method on the Toshiba 200FR Neo analyzer (Toshiba Medical System Co., Ltd., Tokyo, Japan).
FPG was measured using the immunoturbidimetric method (Toshiba) and the enzymatic colorimetric method, respectively, on the Toshiba 200 FR autoanalyzer (Toshiba). Ion-exchange high-performance liquid chromatography (Bio-Rad Laboratories, Inc., Hercules, CA) was used to measure the HbA1c levels. Definitions of diabetes, prediabetes and non-alcoholic fatty liver disease (NAFLD) Individuals with diabetes were defined as those with a fasting plasma glucose (FPG) level Individuals with diabetes were defined as those with a fasting plasma glucose (FPG) level of 7.0 mmol/L and/ or HbA1c level of In addition, participants who reported the use of antidiabetic medication on a self-report questionnaire were considered to have diabetes 23).
Liver ultrasound was performed for the diagnosis of NAFLD (Ultrasound Systems IU22, Philips, The Netherlands) based on experience. The diagnosis of fatty liver was established on the basis of characteristic ultrasound features consistent with a "bright liver" and obvious contrast between the liver and kidney parenchyma, blurring of vessels, focal sparing and narrowing of the lumen of the hepatic veins 2). Continuous variables with normal distributions are expressed as mean ± standard deviation, while continuous variables with skewed distributions are expressed as median (and interquartile range). Demographic and biochemical characteristics of subgroups categorized by NAFLD status or outcomes were compared by Student's t test or Mann–Whitney U test for continuous variables or χ2 test for categorical variables.
Multivariable Cox proportional hazard model was performed to estimate RR and 95% confidence intervals (CIs) for diabetes with NAFLD status. All statistical analyzes were performed using SPSS software (version 21.0 for Windows; SPSS, Inc., Chicago, IL).
Results
- Baseline characteristics of the participants according to the presence of NAFLD status
- Comparison of baseline characteristics according to the outcomes
- Relative risks (RRs) of diabetes according to NAFLD and waist circumference changes Multivariate models for the development of diabetes in subjects with prediabetes
- RRs of diabetes according to NAFLD and BMI changes
BMI stands for body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c;. LDL cholesterol, low-density lipoprotein cholesterol; HDL cholesterol, high-density lipoprotein cholesterol; AST, aspartate aminotransferase; ALT, alanine aminotransferase. A total of 6,240 subjects with prediabetes were classified into two subgroups based on the following outcomes (1) subjects who developed diabetes (n control groups (n) Baseline characteristics of subjects according to subgroups are shown in Table 2.
Furthermore, subjects who developed diabetes were significantly male-dominant and had a higher rate of current smoking, overweight/obesity, hypertension, and especially a higher rate of NAFLD (P<0.001; . Table 2). Blood pressure, total cholesterol, LDL-cholesterol and creatinine levels did not differ between groups. BMI indicates body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HbA1c, hemoglobin A1c; LDL cholesterol, low-density lipoprotein cholesterol; HDL cholesterol, high-density lipoprotein cholesterol; AST, aspartate aminotransferase;.
The prevalence of diabetes in subjects with prediabetes according to baseline NAFLD status is shown in table 3. In addition, the corresponding incidence density was 2.27 per 100 person-years in subjects with NAFLD and 1.38 per 100 person-years in subjects without NAFLD. Relative risks (RRs) of diabetes according to NAFLD and waist circumference changes Multivariate models for the development of diabetes in subjects with prediabetes Multivariate models for the development of diabetes in subjects with prediabetes (Table 4) showed that the presence of NAFLD was a significant independent risk factor.
RRs were lower for those whose WC changes were ≤ 0.0 cm, and RRs were higher for those with a larger waist circumference at follow-up. When subgroups were divided into three different groups, i.e. WC changes < -1.0 cm, -1.0 to 1.0 cm and > 1.0 cm, the corresponding RRs were similar and also closely related to WC- changes. RRs and 95% CI of diabetes by NAFLD and changes in waist circumference (WC) (tertile stratification).
When the baseline model was adjusted for age, smoking, alcohol consumption, BMI, WC, ALT, and hypertension, the RRs for diabetes were closely related to changes in BMI.
Discussion
Because most previous studies focused on subjects without diabetes, this study filled the gaps of this relationship among subjects with prediabetes. Furthermore, the results showed consistent findings, meaning that even in prediabetic patients with NAFLD, there are still positive correlations between NAFLD and diabetes. In this study, we investigated the impact of WC changes on the relationship between NAFLD and diabetes in subjects with prediabetes.
In tertile stratification, RRs were lower for subjects who had the same or decreased WC during follow-up, and RRs were higher for those with increased WC. In addition, we also investigated the impact of BMI changes on the relationship between NAFLD and diabetes in a subject with prediabetes. A Japanese cohort study showed that there was a significant reduction in the incidence of diabetes in a group with a reduced BMI25).
A 5-year cohort study based on 18,507 Chinese elderly showed that RRs of NAFLD for diabetes and prediabetes were related to BMI changes29). Whether a BMI decrease improves the degree of hepatic steatosis or a BMI decrease has an effect on both NAFLD and diabetes is difficult to determine precisely. Alternatively, although the mechanisms are unclear, we can still conclude that for NAFLD patients who had decreased BMI, the RRs were lower compared to those with.
Second, we analyzed the impact of WC and BMI changes on the relationship between NAFLD and diabetes. In addition, the subgroup analysis clearly showed how BMI changes influenced the RRs of NAFLD with diabetes prediabetes. Fifth, we could not include dietary habits as one of the potential confounders in the development of type 2 diabetes in our fitted models because we did not collect them.
This may lead to inaccuracy in the estimated RRs for incident type 2 diabetes. Finally, the lack of a 2-hour oral glucose tolerance test may have resulted in the inclusion of subjects with undiagnosed type 2 diabetes. in the beginning. Despite the above limitations, our study included a large number of subjects with prediabetes and evaluated the risk of NAFLD for diabetes and the impact of changes in WC and BMI in prediabetes.
Conclusion
Non-alcoholic fatty liver disease (NAFLD) and its association with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Combined effect of non-alcoholic fatty liver disease and reduced fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study. Non-alcoholic fatty liver disease is a risk factor for type 2 diabetes in middle-aged Japanese men.
Prevalence of nonalcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Abdominal obesity phenotypes and cardiovascular disease risk during a decade of follow-up: the Tehran lipid and glucose study. Risk of incident type 2 diabetes in a Korean metabolically healthy obese population: role of systemic inflammation.
Risk of type 2 diabetes in patients with nonalcoholic fatty liver disease: causation or epiphenomenon. Independent association between improvement in nonalcoholic fatty liver disease and reduced incidence of type 2 diabetes. Clinical availability of nonalcoholic fatty liver disease as an early predictor of type 2 diabetes mellitus in Korean men: a 5-year prospective cohort study.
P0996: The effects of short-term exenatide on circulating adiponectin levels in patients with type 2 diabetes mellitus (DMT2) with or without nonalcoholic fatty liver disease (NAFLD): a randomized, open-label, controlled intervention trial.
