title: Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes.
abstract: Nonalcoholic steatohepatitis (NASH) is increasingly common in obese patients. However, its metabolic consequences in patients with type 2 diabetes mellitus (T2DM) are unknown.
  
  
  
  We studied 154 obese patients divided in four groups: 1) control (no T2DM or NAFLD), 2) T2DM without NAFLD, 3) T2DM with isolated steatosis, and 4) T2DM with NASH. We evaluated intrahepatic triglycerides by proton MRS ((1)H-MRS) and assessed insulin secretion/resistance during an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp with glucose turnover measurements.
  
  
  
  No significant differences among groups were observed in sex, BMI, or total body fat. Metabolic parameters worsened progressively with the presence of T2DM and the development of hepatic steatosis, with worse hyperinsulinemia, insulin resistance, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol) in those with NASH (P < 0.001). Compared with isolated steatosis, NASH was associated with more dysfunctional and insulin-resistant adipose tissue (either as insulin suppression of plasma FFA [33 ± 3 vs. 48 ± 6%] or adipose tissue insulin resistance index [9.8 ± 1.0 vs. 5.9 ± 0.8 mmol/L ⋅ µIU/mL]; both P < 0.03). Furthermore, insulin suppression of plasma FFA correlated well with hepatic steatosis (r = -0.62; P < 0.001) and severity of steatohepatitis (rs = -0.52; P < 0.001). Hepatic insulin sensitivity was also more significantly impaired among patients with T2DM and NASH, both fasting and with increasing insulin levels within the physiological range (10 to 140 µIU/mL), compared with other groups.
  
  
  
  In obese patients with T2DM, the presence of NAFLD is associated with more severe hyperinsulinemia, dyslipidemia, and adipose tissue/hepatic insulin resistance compared with patients without NAFLD. The unfavorable metabolic profile linked to NAFLD should prompt strategies to identify and treat this population early on.
authors: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL Department of Medicine, University of Florida, Gainesville, FL.
authors: Romina
authors: R
authors: Lomonaco
authors: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL.
authors: Fernando
authors: F
authors: Bril
authors: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL.
authors: Paola
authors: P
authors: Portillo-Sanchez
authors: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors: Carolina
authors: C
authors: Ortiz-Lopez
authors: Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX.
authors: Beverly
authors: B
authors: Orsak
authors: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL.
authors: Diane
authors: D
authors: Biernacki
authors: Department of Medicine, University of Florida, Gainesville, FL.
authors: Margaret
authors: M
authors: Lo
authors: Division of Gastroenterology, Hepatology, and Nutrition, Malcom Randall VA Medical Center, Gainesville, FL.
authors: Amitabh
authors: A
authors: Suman
authors: Division of Pathology, Malcom Randall VA Medical Center, Gainesville, FL.
authors: Michelle H
authors: MH
authors: Weber
authors: Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL Division of Endocrinology, Malcom Randall VA Medical Center, Gainesville, FL kenneth.cusi@medicine.ufl.edu.
authors: Kenneth
authors: K
authors: Cusi
mesh_terms: D050154:Adiposity; D000328:Adult; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D050171:Dyslipidemias / Q000097:blood / Q000150:complications; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D009765:Obesity / Q000097:blood* / Q000150:complications; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D014280:Triglycerides