Regional Fat Depots and Insulin Resistance

NCT ID: NCT01336777

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 166 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2013-05-31

Brief Summary

The biological basis for insulin resistance associated with obesity is unknown. By studying equally-overweight/obese individuals who are either insulin resistant or insulin sensitive, the investigators will compare characteristics of fat tissue to test several hypotheses: 1) impaired differentiation and fat storage in the subcutaneous fat depot characterize insulin resistant individuals, who have, as a result, fat in other tissues like liver and muscle, as well as more fat circulating in the blood; 2) inflammation is greater in visceral and/or subcutaneous adipose tissue depots in insulin resistant individuals as compared with insulin sensitive individuals.

Detailed Description

Insulin resistance (IR) is a major contributor to obesity-related morbidities such as diabetes and cardiovascular disease. While obesity is associated with IR, the biological basis for this association is unclear, and not all obese individuals are IR. The once-popular portal hypothesis, which states that lipolysis from VAT in particular accounts for IR, has been questioned because VAT contributes only 15% of the total systemic free fatty acid (FFA) flux. Other proposed mechanisms linking obesity to IR include inflammation, adiponectin, and ectopic fat. It is unclear whether VAT mass is more closely linked to IR than is subcutaneous adipose tissue (SAT) mass. Furthermore, evidence linking differential biological activity to IR in VAT or SAT is indirect, largely derived from studies comparing lean to obese or VAT to SAT without evaluation of IR. Thus, the purpose of this study is to investigate the biological mechanisms by which SAT and/or VAT contribute to IR. Specifically, the investigators will explore two related hypotheses- that impaired adipocyte differentiation in SAT is related to IR, ectopic fat deposition and expansion of VAT depot, and that inflammation in VAT is associated with IR. Utilizing adipose cell size/distribution obtained by Beckman Coulter Multisizer, gene expression via quantitative PCR, in-vivo quantification of IR via a modified insulin suppression test, and CT scans of abdomen/thigh, our specific aims are to:

1. Confirm that impairment of adipocyte differentiation in SAT is associated with IR by comparing cell size characteristics and differentiation markers in IR and IS subjects undergoing elective surgery;

2. Test the hypothesis that the same relationship will not be seen in VAT;

3. Demonstrate that VAT mass is expanded in the presence of impaired differentiation of adipocytes in SAT;

4. Demonstrate that intramuscular fat is related to both IR and impaired differentiation of adipocytes in SAT using cell size characteristics and differentiation markers;

5. Demonstrate that increased inflammation in omental fat is associated with IR independent of obesity using inflammation markers (gene and protein).

Conditions

Obesity; Insulin Resistance; Diabetes Mellitus Type 2

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Insulin resistant group

there is no intervention

No interventions assigned to this group

Insulin sensitive group

There is no intervention

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• No major organ disease
• Fasting blood glucose < 126 mg/dL
• BMI 25-35 kg/m2
• Nonpregnant/nonlactating

Exclusion Criteria

• pregnancy/lactation
• major organ disease
• drugs that influence insulin resistance
• unstable body weight or active weight loss program
• outside BMI range or age range
• diabetic by fasting glucose criteria 126 mg/dL or higher

• Minimum Eligible Age: 39 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Tracey McLaughlin

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Stanford University

Stanford, California, United States

Countries

United States

References

McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011 Nov;96(11):E1756-60. doi: 10.1210/jc.2011-0615. Epub 2011 Aug 24.

Reference Type: DERIVED

PMID: 21865361 (View on PubMed)

Other Identifiers

1R01DK080436

Identifier Type: NIH

Identifier Source: org_study_id

View Link