Insulin Resistance in Nonalcoholic Fatty Liver Disease: A Case Control Study

NCT00637520 | Terminated

• 3 other identifiers: Pro00006742NIH K23 Award8592
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

We hypothesize that insulin resistance is characteristic of nonalcoholic fatty liver disease as compared to age, gender, non-diabetic BMI-matched control subjects, both healthy and those with non-cirrhotic, non-steatotic liver disease.

Conditions

Insulin Resistance; Nonalcoholic Fatty Liver Disease

Keywords

Nonalcoholic Fatty Liver Disease; Insulin Resistance; Lipid Metabolism

Outcome Measures

Primary Outcomes (3)

• Measure Insulin Resistance (IR) and clearance its effects on lipid metabolism, inflammatory response, and oxidative stress using intravenous glucose tolerance testing in patients with NAFLD as compared to matched controls.

  36 months

• Determine if IR is associated with altered parameters of lipid metabolism as compared to matched controls

  36 months

• Measure the differential effects of IR and lipid metabolism on peripheral mononuclear cell (PBMC) inflammatory response and the associated hepatocyte mitochondrial ultrastructure and measures of oxidative stress.

  36 Months

Study Arms (3)

1

Subjects with NAFLD

2

Subjects without liver disease

3

Subjects with non-steatotic hepatitis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Liver Clinic, Liver Transplant Clinic, Weight Loss Surgery Clinic

You may qualify if:

• Biochemical and liver histologic features to confirm the presence of a healthy liver, fatty liver, and/or non-fatty liver with inflammation due to another etiology besides NAFLD.

You may not qualify if:

• \> 20 grams of alcohol/day
• Impaired oral glucose tolerance test
• Clinical or histologic evidence of cirrhosis (stage 5-6 fibrosis) or portal hypertension.
• Chronic hepatitis C infection
• Known diabetes mellitus or need for insulin-sensitizing agents and/or insulin therapy.
• Pregnancy

Sponsors & Collaborators

• Duke University: lead
• University of Florida: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (18)

• Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med. 1999 Nov;107(5):450-5. doi: 10.1016/s0002-9343(99)00271-5.

  PMID: 10569299 BACKGROUND

• Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, Khalil L, Turpin G, Opolon P, Poynard T. Liver fibrosis in overweight patients. Gastroenterology. 2000 Jun;118(6):1117-23. doi: 10.1016/s0016-5085(00)70364-7.

  PMID: 10833486 BACKGROUND

• Silverman JF, Pories WJ, Caro JF. Liver pathology in diabetes mellitus and morbid obesity. Clinical, pathological, and biochemical considerations. Pathol Annu. 1989;24 Pt 1:275-302. No abstract available.

  PMID: 2654841 BACKGROUND

• Kern WH, Heger AH, Payne JH, DeWind LT. Fatty metamorphosis of the liver in morbid obesity. Arch Pathol. 1973 Nov;96(5):342-6. No abstract available.

  PMID: 4741905 BACKGROUND

• Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002 Apr 18;346(16):1221-31. doi: 10.1056/NEJMra011775. No abstract available.

  PMID: 11961152 BACKGROUND

• Chitturi S, Abeygunasekera S, Farrell GC, Holmes-Walker J, Hui JM, Fung C, Karim R, Lin R, Samarasinghe D, Liddle C, Weltman M, George J. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002 Feb;35(2):373-9. doi: 10.1053/jhep.2002.30692.

  PMID: 11826411 BACKGROUND

• Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003 Apr;37(4):917-23. doi: 10.1053/jhep.2003.50161.

  PMID: 12668987 BACKGROUND

• Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, Cassader M, David E, Cavallo-Perin P, Rizzetto M. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002 Feb;35(2):367-72. doi: 10.1053/jhep.2002.30690.

  PMID: 11826410 BACKGROUND

• Ikai E, Ishizaki M, Suzuki Y, Ishida M, Noborizaka Y, Yamada Y. Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. J Hum Hypertens. 1995 Feb;9(2):101-5.

  PMID: 7752170 BACKGROUND

• DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. 1991 Mar;14(3):173-94. doi: 10.2337/diacare.14.3.173.

  PMID: 2044434 BACKGROUND

• Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001 Aug;50(8):1844-50. doi: 10.2337/diabetes.50.8.1844.

  PMID: 11473047 BACKGROUND

• Bacon BR, Farahvash MJ, Janney CG, Neuschwander-Tetri BA. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology. 1994 Oct;107(4):1103-9. doi: 10.1016/0016-5085(94)90235-6.

  PMID: 7523217 BACKGROUND

• Lee JH, Rhee PL, Lee JK, Lee KT, Kim JJ, Koh KC, Paik SW, Rhee JC, Choi KW. Role of hyperinsulinemia and glucose intolerance in the pathogenesis of nonalcoholic fatty liver in patients with normal body weight. Korean J Intern Med. 1998 Feb;13(1):12-4.

  PMID: 9538625 BACKGROUND

• Expert Committee on the Diagnosis and Clasification of Diabetes Mellitus. American Diabetes Association: clinical practice recommendations 2002. Diabetes Care. 2002 Jan;25 Suppl 1:S1-147. doi: 10.2337/diacare.25.2007.s1. No abstract available.

  PMID: 11788484 BACKGROUND

• Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004 Dec;114(12):1752-61. doi: 10.1172/JCI21625.

  PMID: 15599400 BACKGROUND

• Manes JL, Taylor HB, Starkloff GB. Relationship between hepatic morphology and clinical and biochemical findings in morbidly obese patients. J Clin Pathol. 1973 Oct;26(10):776-83. doi: 10.1136/jcp.26.10.776.

  PMID: 4750460 BACKGROUND

• Kaneda M, Kashiwamura S, Ueda H, Sawada K, Sugihara A, Terada N, Kimura-Shimmyo A, Fukuda Y, Shimoyama T, Okamura H. Inflammatory liver steatosis caused by IL-12 and IL-18. J Interferon Cytokine Res. 2003 Mar;23(3):155-62. doi: 10.1089/107999003321532493.

  PMID: 12716488 BACKGROUND

• Khaodhiar L, Ling PR, Blackburn GL, Bistrian BR. Serum levels of interleukin-6 and C-reactive protein correlate with body mass index across the broad range of obesity. JPEN J Parenter Enteral Nutr. 2004 Nov-Dec;28(6):410-5. doi: 10.1177/0148607104028006410.

  PMID: 15568287 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Frozen tissue, serum, whole blood, urine

MeSH Terms

Conditions

Insulin Resistance; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Manal F Abdelmalek, MD., MPH

  Faculty Member

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2008
• First Posted: March 18, 2008
• Study Start: July 1, 2007
• Primary Completion: March 29, 2013
• Study Completion: April 13, 2017
• Last Updated: July 11, 2017

Record last verified: 2016-09

Locations

US (1)