Effects of Moderate Weight Loss and Orlistat on Insulin Resistance, Regional Adiposity, and Fatty Acids in Type 2 Diabetes

  1. David E. Kelley, MD1,
  2. Lewis H. Kuller, MD, DRPH2,
  3. Therese M. McKolanis, MPH1,
  4. Patricia Harper, MS, RD1,
  5. Juliet Mancino, MS, RD, CDE1 and
  6. Satish Kalhan, MD3
  1. 1Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania
  2. 2Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
  3. 3Schwartz Center and Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
  1. Address correspondence and reprint requests to David E. Kelley, MD, Professor of Medicine, 810N Montefiore-University Hospital, University of Pittsburgh, 3459 Fifth Ave., Pittsburgh, PA 15213. E-mail: kelley{at}msx.dept-med.pitt.edu

Abstract

OBJECTIVE—Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss–dependent and –independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).

RESEARCH DESIGN AND METHODS—Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (−10.3 ± 1.3 vs. −8.9 ± 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.

RESULTS—Weight loss resulted in substantial improvement (P < 0.001) in HbA1c (−1.6 ± 0.3 vs. −1.0 ± 0.4%; NS between groups). IS improved significantly more with orlistat (Δ2.2 ± 0.4 vs. Δ1.2 ± 0.4 mg · min−1 · kg−1 fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Δ–154 ± 22 vs. Δ–51 ± 33 μmol/l; P < 0.05), insulin-suppressed FFA (Δ–119 ± 23 vs. Δ–87 ± 34 μmol/l; P < 0.05), and fasting plasma glucose (FPG; −62 ± 9 vs. −32 ± 8 mg/dl; P = 0.02). Changes in HbA1c were correlated with ΔIS (r = −0.41; P < 0.01) but not with weight loss per se.

CONCLUSIONS—At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS.

Footnotes

  • D.E.K. is a member of an advisory panel/standing committee/board of directors of Roche, Novartis, Takeda, and GlaxoSmithKline and has received honoraria/consulting fees as well as grant/research support from Roche, Novartis, GlaxoSmithKline, and Pfizer.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted September 23, 2003.
    • Received May 19, 2003.
« Previous | Next Article »Table of Contents

This Article

  1. doi: 10.2337/diacare.27.1.33 Diabetes Care January 2004 vol. 27 no. 1 33-40
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)

Current Issue

  1. November 2009, 32 (11)
  1. Current Issue
  1. Alert me to new issues of Diabetes Care