PMID- 26861926
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20220311
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 39
IP  - 4
DP  - 2016 Apr
TI  - Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 
      Diabetes.
PG  - 632-8
LID - 10.2337/dc15-1876 [doi]
AB  - OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is increasingly common in obese 
      patients. However, its metabolic consequences in patients with type 2 diabetes 
      mellitus (T2DM) are unknown. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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 ⋅ microIU/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 microIU/mL), compared with 
      other groups. CONCLUSIONS: 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.
CI  - (c) 2016 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.
FAU - Lomonaco, Romina
AU  - Lomonaco R
AD  - Division of Endocrinology, Diabetes and Metabolism, University of Florida, 
      Gainesville, FL Department of Medicine, University of Florida, Gainesville, FL.
FAU - Bril, Fernando
AU  - Bril F
AD  - Division of Endocrinology, Diabetes and Metabolism, University of Florida, 
      Gainesville, FL.
FAU - Portillo-Sanchez, Paola
AU  - Portillo-Sanchez P
AD  - Division of Endocrinology, Diabetes and Metabolism, University of Florida, 
      Gainesville, FL.
FAU - Ortiz-Lopez, Carolina
AU  - Ortiz-Lopez C
AD  - Division of Diabetes, University of Texas Health Science Center at San Antonio, 
      San Antonio, TX.
FAU - Orsak, Beverly
AU  - Orsak B
AD  - Division of Diabetes, University of Texas Health Science Center at San Antonio, 
      San Antonio, TX.
FAU - Biernacki, Diane
AU  - Biernacki D
AD  - Division of Endocrinology, Diabetes and Metabolism, University of Florida, 
      Gainesville, FL.
FAU - Lo, Margaret
AU  - Lo M
AD  - Department of Medicine, University of Florida, Gainesville, FL.
FAU - Suman, Amitabh
AU  - Suman A
AD  - Division of Gastroenterology, Hepatology, and Nutrition, Malcom Randall VA 
      Medical Center, Gainesville, FL.
FAU - Weber, Michelle H
AU  - Weber MH
AD  - Division of Pathology, Malcom Randall VA Medical Center, Gainesville, FL.
FAU - Cusi, Kenneth
AU  - Cusi K
AD  - 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.
LA  - eng
GR  - I01 CX000167/CX/CSRD VA/United States
GR  - UL1 RR025767/RR/NCRR NIH HHS/United States
PT  - Journal Article
DEP - 20160209
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Insulin)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Adiposity
MH  - Adult
MH  - Body Mass Index
MH  - Cholesterol, HDL/blood
MH  - Cholesterol, LDL/blood
MH  - Cohort Studies
MH  - Diabetes Mellitus, Type 2/*blood/complications
MH  - Dyslipidemias/blood/complications
MH  - Female
MH  - Glucose Clamp Technique
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Hyperinsulinism/blood/complications
MH  - Insulin/blood/metabolism
MH  - Insulin Resistance
MH  - Insulin Secretion
MH  - Male
MH  - Middle Aged
MH  - Non-alcoholic Fatty Liver Disease/*blood/complications
MH  - Obesity/*blood/complications
MH  - Triglycerides/blood
PMC - PMC5864108
EDAT- 2016/02/11 06:00
MHDA- 2017/10/24 06:00
PMCR- 2017/04/01
CRDT- 2016/02/11 06:00
PHST- 2015/08/27 00:00 [received]
PHST- 2016/01/07 00:00 [accepted]
PHST- 2016/02/11 06:00 [entrez]
PHST- 2016/02/11 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - dc15-1876 [pii]
AID - 1876 [pii]
AID - 10.2337/dc15-1876 [doi]
PST - ppublish
SO  - Diabetes Care. 2016 Apr;39(4):632-8. doi: 10.2337/dc15-1876. Epub 2016 Feb 9.