The Association of Fatty Liver and Diabetes Risk

We examined whether fatty liver, as diagnosed with abdominal ultrasonography, is an independent risk factor for diabetes mellitus during 10 years of follow-up. A total of 840 subjects (467 men and 373 women) were followed for the entire 10 years. The criteria for being non-diabetic were having no history of diabetes, having a fasting plasma glucose level of less than 110 mg/dl and a serum hemoglobin A1c level of 6.4% or less. We indicated that every examine received all examinations after 12 hours of fasting. Well-trained technicians performed abdominal ultrasonography. Although univariate analysis revealed that the presence of fatty liver was related to hyperglycemia 10 years later, multiple logistic regression analysis did not support this finding. In the multiple logistic regression analysis fasting plasma glucose levels at the baseline and age were significantly related to hyperglycemia (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.11-1.21, OR = 1.07, 95% CI: 1.01-1.14, respectively). Fatty liver was not an independent risk factor for hyperglycemia in our follow-up study 10 years after the first diagnosis. The high fasting plasma glucose levels were a risk factor for diabetes, even in the normal range.

Recently, the prevalence of diabetes mellitus and related deaths have increased in Japan. The 1997 Ministry of Health and Welfare investigation estimated that there were about 13,700,000 patients with diabetes in Japan, of which only about 6,900,000 had been diagnosed.1 Many of the patients were type 2 diabetes mellitus, and the importance of preventive care has been emphasized. Type 2 diabetes mellitus is mainly associated with obesity; however, it has also been shown to be associated with a fatty liver.
A fatty liver or steatohepatitis is the most common liver disease2 and its incidence has increased recently in Japan,3 especially in those between the ages of 40 and 50 years. 4 Although the etiology of fatty liver and nonalcoholic steatohepatitis (NASH) are not completely known, studies indicate that steatohepatitis and fatty liver are related to obesity,3,5-19 dyslipidemia, 5,8,9,12-14.16-18.20 type 2 diabetes mellitus, 8-11,13,17,20,21 leptin,5,15 and insulin resistance. [16][17][18][19][20][21][22][23][24] Most of these studies were case-control and cross-sectional studies. A cohort study suggested that serum r-glutamyltransferase ( r-GTP) level was an independent risk factor for non-insulin dependent diabetes mellitus (NIDDM). 25 To our knowledge, however, no cohort studies have examined the association between a fatty liver, as diagnosed on ultrasonography, and diabetes risk. Therefore, we examined whether the diagnosis of fatty liver, based on ultrasonographic results, is a risk factor for diabetes over a 10-year follow-up period.

METHODS
A total of 2653 subjects (1491 men and 1162 women) voluntarily visited Yamanashi Kouseiren Medical Center for general check-ups from April 1, 1991 through March 31, 1992.
All the subjects lived in Yamanashi Prefecture, a rural area located about 100 km west of Tokyo. The subjects included agricultural workers, white-collar workers, and business people. All the study participants filled in a self-administered questionnaire about their smoking habits (cigarettes per day, the number of   OR: odds ratio, CI: confidence interval The number of diabetic pattern at the end of follow-up in parentheses.  parental diabetes, and frequency of check-ups, no association was observed. Thus it does not appear that the presence of fatty liver is an independent risk factor for hyperglycemia. Obesity, aging, lack of exercise, genetic factors, and stress are known as risk factors of type 2 diabetes mellitus. 28 In terms of obesity and fatty liver, previous studies have shown that fatty liver occurred more frequently in obese subjects than in normalweight subjects.3,5-19 The BMI levels were significantly higher in the fatty liver group than in the non-fatty liver group in our study. Although there was not difference in age between fatty liver group and non-fatty liver group, Nomura4 showed that the prevalence of fatty liver was higher in 40s than 30s of age. We think that these factors lead to the diminution of the association of fatty liver and hyperglycemia over time.
Our study should be interpreted carefully, however, because of the limitations in the study design. First, our population sample consisted of people who voluntarily decided to have the examinations. They may be more concerned with their health than people who have not received physical check-ups. We do not know how many people have diabetes or fatty liver in our area because no investigation of these people was performed. From this reason, we guessed that the prevalence of hyperglycemia in our study was less than that of the general population in our prefecture. Second, the number of subjects in group A represented about one third of subjects. The members of this group may be particularly concerned with their health or have other health problems. There were no significant differences between groups A and B in terms of the prevalence of fatty liver. However, among women, FPG, TC, and TG levels were significantly lower in the group A than in group B. It is thought that some of the women in group B in this study were diagnosed with diabetes and went to other clinics, so they did not receive a follow-up examination 10 years later. This may be one of the reasons that the prevalence of fatty liver among women in this study was low. The results of multiple regression analysis showed the same results among men and women. Finally, the men and women who were diagnosed with fatty liver had consultations with doctors and nurses. Therefore, there is a high possibility that they changed their eating and exercise habits, which could have influenced the prevalence of diabetes. Thus, the relation between fatty liver and diabetes in our study may be underestimated.
Previous studies 16-19.22-24 reported that there were associated with insulin and hepatic insulin resistance even in the absence of diabetes in subjects with steatohepatitis, fatty liver, and NASH. Perry et all' performed a cohort study and reported that raised r -GTP levels are an independent risk factor for NIDDM. Given the results of previous studies, we suspected that fatty liver leads to future diabetes. Our results showed that fatty liver is associated with diabetes, but is not an independent risk factor for diabetes.
In terms of the diagnosis of fatty liver, a liver biopsy is necessary to precisely diagnose as fatty liver and determine the types of fatty liver diseases. Invasive procedures were not allowed in the present study. Abdominal ultrasonograms are noninvasive and an easy method for examining liver conditions and other organs. A previous study indicated that ultrasonographic detection and quantitative hepatic fat accumulation are similar with computed tomography and liver biopsy.29 A previous study in which ultrasonographic findings were compared with histologic results also indicated that the overall sensitivity and specificity of ultrasonographic examinations for the diagnosis of fatty liver are approximately 80% to 95% and 90% to 95%, respectively. 30