Metabolic Changes Following a 1-year Diet and Exercise Intervention in Patients with Type 2 Diabetes
Jeanine B. Albu; Leonie K. Heilbronn; David E. Kelley; Steven R. Smith; Koichiro Azuma; Evan S. Berk; F. Xavier Pi-Sunyer; Eric Ravussin; the Look AHEAD Adipose Research Group
Jeanine B. Albu; Leonie K. Heilbronn; David E. Kelley; Steven R. Smith; Koichiro Azuma; Evan S. Berk; F. Xavier Pi-Sunyer; Eric Ravussin; the Look AHEAD Adipose Research Group
Abstract
ObjectiveTo 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.
Research Design and MethodsWe 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.
ObjectiveTo 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.
Research Design and MethodsWe 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.
ResultsWeight 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.
ConclusionsPatients 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.
Introduction
Most obese patients with type 2 diabetes have an unfavorable adipose tissue distribution compared with that of similarly obese men and women without type 2 diabetes.[12] We have shown that they manifest proportionally less metabolically protective adipose tissue (gluteo-femoral) and more metabolically adverse fat depots such as abdominal adipose tissue or hepatic fat.[2]
Such patterns correlate with increased fasting glucose and decreased insulin sensitivity[35] in cross-sectional studies. From the perspective of intervention, in type 2 diabetes, both caloric restriction and relatively modest weight reduction result in fasting glucose[610] as well as hepatic[7,9,1113] and peripheral insulin sensitivity[810,1213] improvements. However, not all studies reporting significant weight loss or favorable fat distribution changes have observed a concomitant improvement in peripheral insulin sensitivity.[11,14] Furthermore, there is a surprising paucity of data regarding the relationship between sustained lifestyle interventioninduced changes in fat mass and regional adipose tissue distribution and parallel metabolic improvements.
In several weight loss studies conducted for up to 6 months, in type 2 diabetes favorable changes in fat distribution and organ fat did not correlate with improved peripheral insulin sensitivity independent of the changes in body weight.[1114] Even fewer studies reported on longer-term (of up to 1 year) effects of weight loss on fat distribution and metabolic variables in type 2 diabetes.[10,1516] In one study, while parallel 1-year improvements were observed both in the fat distribution (measured by the waist-to-hip ratio) and in fasting glucose and fasting insulin,[15] the metabolic improvements did not relate to the waist-to-hip ratio change but rather to the overall amount of weight loss.[15]
One interpretation is that loss of adipose tissue, regardless of depot, is the predominant factor related to the metabolic improvement in obese patients with type 2 diabetes, challenging the tenet, built mostly from cross-sectional studies, that adipose tissue distribution is a crucial and interactive determinant of the improvement. Yet, it is not clear from these studies whether the variability of the weight loss, the sometime limited number of subjects, or incomplete adipose tissue distribution measurements permitted robust evaluation of the role of specific fat depots in the improvements in metabolic control. In addition, changes in other adipose tissue characteristics, such as fat cell sizes or circulating free fatty acids (FFAs), have not been accounted for in previous studies. Larger subcutaneous abdominal fat cells predict insulin resistance and the development of type 2 diabetes,[1719] while increased circulating FFAs play an important role in the etiology of insulin resistance and hyperglycemia in type 2 diabetes.[12,2021] Whether regional fat loss contributes to improvements in FFAs during weight loss in type 2 diabetes has not previously been reported.
The current study was therefore undertaken to examine the importance of changes in adipose tissue distribution and other closely related characteristics as determinants of the improvements in metabolic fitness in response to weight loss in type 2 diabetes. We tested the hypothesis that simple measures of weight loss rather than various relative changes and permutations of adipose tissue distribution are the predominant determinant of metabolic improvement induced by a 1-year lifestyle intervention in obese patients with type 2 diabetes. Multiple aspects of adipose tissue mass and its distribution were assessed, including upper and lower adipose tissue mass (using dual-energy X-ray absorptiometry [DEXA]), adipose tissue subdivisions in the abdomen and lower extremity (using computed tomography [CT] imaging), and estimations of fat content in liver and muscle (using CT imaging). This was performed along with an adipose tissue biopsy in order to measure mean fat cell size within the abdominal subcutaneous depot both at baseline and following the 1 year of lifestyle intervention.
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Introduction
Most obese patients with type 2 diabetes have an unfavorable adipose tissue distribution compared with that of similarly obese men and women without type 2 diabetes.[12] We have shown that they manifest proportionally less metabolically protective adipose tissue (gluteo-femoral) and more metabolically adverse fat depots such as abdominal adipose tissue or hepatic fat.[2]
Such patterns correlate with increased fasting glucose and decreased insulin sensitivity[35] in cross-sectional studies. From the perspective of intervention, in type 2 diabetes, both caloric restriction and relatively modest weight reduction result in fasting glucose[610] as well as hepatic[7,9,1113] and peripheral insulin sensitivity[810,1213] improvements. However, not all studies reporting significant weight loss or favorable fat distribution changes have observed a concomitant improvement in peripheral insulin sensitivity.[11,14] Furthermore, there is a surprising paucity of data regarding the relationship between sustained lifestyle interventioninduced changes in fat mass and regional adipose tissue distribution and parallel metabolic improvements.
In several weight loss studies conducted for up to 6 months, in type 2 diabetes favorable changes in fat distribution and organ fat did not correlate with improved peripheral insulin sensitivity independent of the changes in body weight.[1114] Even fewer studies reported on longer-term (of up to 1 year) effects of weight loss on fat distribution and metabolic variables in type 2 diabetes.[10,1516] In one study, while parallel 1-year improvements were observed both in the fat distribution (measured by the waist-to-hip ratio) and in fasting glucose and fasting insulin,[15] the metabolic improvements did not relate to the waist-to-hip ratio change but rather to the overall amount of weight loss.[15]
One interpretation is that loss of adipose tissue, regardless of depot, is the predominant factor related to the metabolic improvement in obese patients with type 2 diabetes, challenging the tenet, built mostly from cross-sectional studies, that adipose tissue distribution is a crucial and interactive determinant of the improvement. Yet, it is not clear from these studies whether the variability of the weight loss, the sometime limited number of subjects, or incomplete adipose tissue distribution measurements permitted robust evaluation of the role of specific fat depots in the improvements in metabolic control. In addition, changes in other adipose tissue characteristics, such as fat cell sizes or circulating free fatty acids (FFAs), have not been accounted for in previous studies. Larger subcutaneous abdominal fat cells predict insulin resistance and the development of type 2 diabetes,[1719] while increased circulating FFAs play an important role in the etiology of insulin resistance and hyperglycemia in type 2 diabetes.[12,2021] Whether regional fat loss contributes to improvements in FFAs during weight loss in type 2 diabetes has not previously been reported.
The current study was therefore undertaken to examine the importance of changes in adipose tissue distribution and other closely related characteristics as determinants of the improvements in metabolic fitness in response to weight loss in type 2 diabetes. We tested the hypothesis that simple measures of weight loss rather than various relative changes and permutations of adipose tissue distribution are the predominant determinant of metabolic improvement induced by a 1-year lifestyle intervention in obese patients with type 2 diabetes. Multiple aspects of adipose tissue mass and its distribution were assessed, including upper and lower adipose tissue mass (using dual-energy X-ray absorptiometry [DEXA]), adipose tissue subdivisions in the abdomen and lower extremity (using computed tomography [CT] imaging), and estimations of fat content in liver and muscle (using CT imaging). This was performed along with an adipose tissue biopsy in order to measure mean fat cell size within the abdominal subcutaneous depot both at baseline and following the 1 year of lifestyle intervention.
DOWNLOAD PDF COMPLETE HERE
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