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      Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study

      research-article
      , MRCP 1 , , MD, FFPH 2 , , FRCR 3 , , MRCP, FRCR 3 , , GRADDIPPAPPSCI 3 , , PHD, MD 4 , , MD, FRCPE 5 , , MRCP 1 , , PHD 6 , , PHD, FRCPE 7 , , MD, FRCPE 1 , on behalf of the Edinburgh Type 2 Diabetes Study Investigators
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          Type 2 diabetes is an established risk factor for development of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and clinical correlates of these conditions in a large cohort of people with type 2 diabetes.

          RESEARCH DESIGN AND METHODS

          A total of 939 participants, aged 61–76 years, from the Edinburgh Type 2 Diabetes Study (ET2DS)—a large, randomly selected population of people with type 2 diabetes—underwent liver ultrasonography. Ultrasound gradings of steatosis were compared with magnetic resonance spectroscopy in a subgroup. NAFLD was defined as hepatic steatosis in the absence of a secondary cause (screened by questionnaire assessing alcohol and hepatotoxic medication use, plasma hepatitis serology, autoantibodies and ferritin, and record linkage to determine prior diagnoses of liver disease). Binary logistic regression was used to analyze independent associations of characteristics with NAFLD.

          RESULTS

          Hepatic steatosis was present in 56.9% of participants. After excluding those with a secondary cause for steatosis, the prevalence of NAFLD in the study population was 42.6%. Independent predictors of NAFLD were BMI, lesser duration of diabetes, HbA 1c, triglycerides, and metformin use. These remained unchanged after exclusion of participants with evidence of hepatic fibrosis from the group with no hepatic steatosis.

          CONCLUSIONS

          Prevalences of hepatic steatosis and NAFLD were high in this unselected population of older people with type 2 diabetes, but lower than in studies in which ultrasound gradings were not compared with a gold standard. Associations with features of the metabolic syndrome could be used to target screening for this condition.

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          Most cited references16

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          Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.

          An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% CI: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features.
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            Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.

            Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
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              International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis.

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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                May 2011
                20 April 2011
                : 34
                : 5
                : 1139-1144
                Affiliations
                [1] 1Metabolic Unit, Western General Hospital, Edinburgh, U.K.
                [2] 2Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, U.K.
                [3] 3Department of Radiology, Western General Hospital, Edinburgh, U.K.
                [4] 4Department of Hepatology, Royal Infirmary of Edinburgh, Edinburgh, U.K.
                [5] 5Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, U.K.
                [6] 6Pfizer Global R&D, Sandwich, Kent, U.K. and
                [7] 7Endocrinology Unit, University/BHF Centre for Cardiovascular Science, University of Edinburgh, Queens Medical Research Institute, Edinburgh, U.K.
                Author notes
                Corresponding author: Rachel M. Williamson, rachel_m_williamson@ 123456hotmail.com .
                Article
                2229
                10.2337/dc10-2229
                3114489
                21478462
                7e02f9a2-0c02-4fea-8be1-794c1c692049
                © 2011 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 27 November 2010
                : 1 February 2011
                Categories
                Original Research
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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