Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes.
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).


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content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization.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 HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 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 (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (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.
Kelley
David E
DE
Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. kelley@msx.dept-med.pitt.edu
Kuller
Lewis H
LH
McKolanis
Therese M
TM
Harper
Patricia
P
Mancino
Juliet
J
Kalhan
Satish
S
D000273:Adipose Tissue / Q000033:anatomy & histology*; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D007783:Lactones / Q000627:therapeutic use*; D009765:Obesity; D000077403:Orlistat; D010919:Placebos; D013997:Time Factors; D015431:Weight Loss / Q000502:physiology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007783:Lactones; D010919:Placebos; D000077403:Orlistat; D005947:Glucose