Metabolic changes following a 1-year diet and exercise intervention in patients with type 2 diabetes.
OBJECTIVE
To characterize the relationships among long-term improvements in peripheral insulin sensitivity (glucose disposal rate [GDR]), fasting glucose, and free fatty acids (FFAs) and concomitant changes in weight and adipose tissue mass and distribution induced by lifestyle intervention in obese individuals with type 2 diabetes.


METHODS
We measured GDR, fasting glucose, and FFAs during a euglycemic clamp and adipose tissue mass and distribution, organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and after 1 year of diet and exercise aimed at weight loss.


RESULTS
Weight and fasting glucose decreased significantly (P < 0.0001) and significantly more in men than in women (-12 vs. -8% and -16 vs. -7%, respectively; P < 0.05), while FFAs during hyperinsulinemia decreased and GDR increased significantly (P < 0.00001) and similarly in both sexes (-53 vs. -41% and 63 vs. 43%; P = NS). Men achieved a more favorable fat distribution by losing more from upper compared with lower and from deeper compared with superficial adipose tissue depots (P < 0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR but not in fasting glucose or fasting FFAs; however, decreases in FFAs during hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the only regional fat measure whose change contributed independently to changes in metabolic variables.


CONCLUSIONS
Patients with type 2 diabetes undergoing a 1-year lifestyle intervention had significant improvements in GDR, fasting glucose, FFAs and adipose tissue distribution. However, changes in overall weight (adipose tissue mass) and hepatic fat were the most important determinants of metabolic improvements.
Albu
Jeanine B
JB
Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University, New York, New York, USA. jba1@columbia.edu
Heilbronn
Leonie K
LK
Kelley
David E
DE
Smith
Steven R
SR
Azuma
Koichiro
K
Berk
Evan S
ES
Pi-Sunyer
F Xavier
FX
Ravussin
Eric
E
D000273:Adipose Tissue / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy* / Q000188:drug therapy / Q000378:metabolism*; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism* / Q000473:pathology; D012737:Sex Factors; D050151:Subcutaneous Fat / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents