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Diabetes Care 27:1756-1758, 2004
© 2004 by the American Diabetes Association, Inc.

Brief Report

Effect of Aerobic Exercise on Plasma Adiponectin Levels and Insulin Resistance in Type 2 Diabetes

Hisayo Yokoyama, MD, Masanori Emoto, MD, PHD, Takahiro Araki, MD, Shigehiko Fujiwara, MD, PHD, Koka Motoyama, MD, PHD, Tomoaki Morioka, MD, PHD, Hidenori Koyama, MD, PHD, Tetsuo Shoji, MD, PHD, Yasuhisa Okuno, MD, PHD and Yoshiki Nishizawa, MD, PHD

From the Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

Address correspondence and reprint requests to Hisayo Yokoyama, MD, Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan, 545-8585. E-mail: fwkx6809{at}mb.infoweb.ne.jp

Abbreviations: clamp-IR, insulin sensitivity index derived from the clamp study • HOMA-IR, insulin sensitivity index derived from homeostasis model assessment


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
Aerobic exercise is a generally accepted therapeutic strategy for type 2 diabetes because it has beneficial effects not only on glycemic profile, but also on reducing metabolic risk factors for cardiovascular diseases including insulin resistance. Previous studies (1,2) have showed the effects of moderate-intensity exercise on the improvement of insulin sensitivity.

Adiponectin, a protein secreted by adipose tissue, presents lower plasma levels in subjects with obesity or type 2 diabetes and is closely correlated with the degree of insulin resistance assessed by the glucose clamp technique (3). Adiponectin also plays a protective role against the development of atherosclerosis by suppressing inflammatory processes on the vascular endothelium (4,5). Therefore, adiponectin is a candidate link between insulin resistance and the high risk of cardiovascular diseases in type 2 diabetes.

To date, however, little is known about whether the improvement in insulin resistance induced by short-term aerobic exercise is associated with changes in plasma adiponectin in type 2 diabetes. Only a few reports (6,7) have examined the acute or chronic effect of high-intensity exercise on plasma adiponectin, mainly in healthy subjects using surrogate insulin resistance indexes. The aim of this study was to assess the effect of aerobic exercise on plasma adiponectin in relation to the improvement of insulin sensitivity in the euglycemic-hyperinsulinemic clamp in type 2 diabetes.


   RESEARCH DESIGN AND METHODS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
The study group included 40 type 2 diabetic subjects aged 54.2 ± 12.6 years (±SD), selected from patients who attend our diabetes center at Osaka City University Hospital. The diagnosis of diabetes was based on the American Diabetes Association criteria (8). No subjects received insulin therapy, and no medications were altered during the exercise treatment. Informed consent was obtained from all participants, and the study was approved by the local ethics committee.

After admission, all subjects underwent a 3-week intervention. Eleven subjects were supervised under medical nutritional therapy alone (energy intake of 25–30 kcal/kg of ideal body wt; D group), and another 29 subjects underwent diet therapy combined with exercise therapy, including bicycle ergometer and walking (EX group). Ergometer exercise was performed for 40 min/day for 5 days/week, at a mean intensity of 50.6 ± 8.6% of maximal heart rate. The patients were also instructed to walk 10,000 steps/day, and the mean number of daily steps was 8,829 ± 3,801.

Before and after intervention, insulin sensitivity was evaluated for all subjects by the homeostasis model assessment (HOMA-IR) (9–11). In the EX group, the evaluation of insulin sensitivity using a euglycemic-hyperinsulinemic clamp was also performed before and after exercise treatment, as fully described previously (10–12). Mean plasma insulin during the steady state of the clamp was 721 ± 204 and 717 ± 183 pmol/l before and after exercise treatment, respectively. The insulin sensitivity index derived from the clamp study (clamp-IR) was calculated by dividing the mean glucose infusion rate during the last 30 min of the clamp by the steady-state plasma insulin and multiplying by 600. Plasma adiponectin was measured by a commercially available enzyme-linked immunosorbent assay kit (Otsuka Pharmaceuticals, Tokyo, Japan) before and after intervention for all subjects. The percentage of body fat was also estimated by bioelectrical impedance analysis, using a body composition analyzer (BC-118; Tanita, Tokyo, Japan).

All values are means ± SD. Statistical analysis was performed using the StatView 5 system (SAS Institute, Cary, NC) for Windows. The Student’s paired t test, simple linear regression analysis, and Spearman’s rank correlation test were used appropriately. P values of <0.05 were considered statistically significant.


   RESULTS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
Before the intervention, there were no significant differences in age, duration of diabetes, BMI, percentage of body fat, and systolic blood pressure between the D and EX groups. Glucose metabolic profiles, including insulin sensitivity assessed by HOMA-IR, were also similar in both groups. The changes in clinical characteristics before and after the study period in both groups are shown in Table 1. Neither BMI, percentage of body fat, nor systolic blood pressure was altered following the 3-week intervention in the D and EX groups. Fasting plasma glucose significantly decreased after intervention in both groups, whereas HbA1c significantly decreased only in the EX group. The insulin sensitivity indexes, HOMA-IR and clamp-IR, were significantly improved after the exercise protocol in the EX group, but no changes in HOMA-IR were observed in the D group. There were no changes in plasma adiponectin following the intervention in either the D or EX group (3.55 ± 1.32 to 3.65 ± 1.54 µg/ml, P = 0.868, and 4.28 ± 1.92 to 4.18 ± 1.72, P = 0.837, respectively).


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  		Table 1— Changes in clinical factors following the intervention

 
In the EX group, plasma adiponectin was significantly positively correlated with clamp-IR before exercise treatment (r = 0.400, P = 0.035). However, the relationship disappeared after intervention. The percentage change in plasma adiponectin following exercise treatment was significantly correlated with that of body weight ({rho} = –0.492, P = 0.009), BMI ({rho} = –0.563, P = 0.003), and percentage of body fat ({rho} = –0.378, P = 0.046), but not with the percentage change in clamp-IR ({rho} = 0.005, P = 0.980) in the EX group.


   CONCLUSIONS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
The present study on 40 type 2 diabetic subjects showed that the improvement in insulin sensitivity induced by short-term aerobic exercise is not mediated by changes in plasma adiponectin, and the results are consistent with the findings of previous observations (6,13) targeting healthy subjects. Based on our findings, we believe that restoring insulin sensitivity by aerobic exercise is mainly mediated by mechanisms other than adiponectin, such as the AMP-activated protein kinase pathway (14). On the other hand, changes in plasma adiponectin are significantly correlated with anthropometrical changes induced by aerobic exercise. Marked weight reduction results in a significant increase in plasma adiponectin levels in obese subjects (15,16); therefore, adiponectin may play a central role in operating insulin action when an improvement of insulin sensitivity is achieved mainly by fat mass reduction. Exercise may indirectly increase plasma adiponectin when an intervention is accompanied by a reduction in body weight or fat mass. Because the role of adiponectin in modifying insulin action varies according to different conditions, further investigations, including elucidating the mechanisms responsible for the adiponectin-mediated recovery of insulin sensitivity, are needed.


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

Received for publication April 1, 2004. Accepted for publication April 3, 2004.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

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  4. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y: Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476, 1999[Abstract/Free Full Text]
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  13. Ryan AS, Nicklas BJ, Berman DM, Elahi D: Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women. Int J Obes Relat Metab Disord 27:1066–1071, 2003[Medline]
  14. Olsen GS, Hansen BF: AMP kinase activation ameliorates insulin resistance induced by free fatty acids in rat skeletal muscle. Am J Physiol Endocrinol Metab 283:E965–E970, 2002[Abstract/Free Full Text]
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