Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online September 21, 2007
Diabetes Care 30:3125-3127, 2007
DOI: 10.2337/dc07-0457
© 2007 by the American Diabetes Association
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc07-0457v1
30/12/3125    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corpeleijn, E.
Right arrow Articles by Blaak, E. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corpeleijn, E.
Right arrow Articles by Blaak, E. E.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Cardiovascular and Metabolic Risk
Original Research

Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes

The Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM)

Eva Corpeleijn, PHD1, Edith J.M. Feskens, PHD2,3, Eugène H.J.M. Jansen, PHD4, Marco Mensink, MD, PHD1, Wim H.M. Saris, MD, PHD1 and Ellen E. Blaak, PHD1

1 Human Biology, Nutrition and Toxicology Research Institute, Maastricht, the Netherlands
2 Human Nutrition, Wageningen University and Research Center, Wageningen, the Netherlands
3 Centre for Nutrition and Health, National Institute for Public Health and Environment, Bilthoven, the Netherlands
4 Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and Environment, Bilthoven, the Netherlands

Address correspondence and reprint requests to Eva Corpeleijn, PHD, Human Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, Netherlands. E-mail: e.corpeleijn{at}hb.unimaas.nl


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
OBJECTIVE—We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin, adiponectin, and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance.

RESEARCH DESIGN AND METHODS—In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht, 147 men and women with impaired glucose tolerance (IGT) were randomized to either a combined diet-and-exercise intervention or a control program. At baseline and after 1 year, an oral glucose tolerance test, an exercise test, and anthropometric measurements were performed. After 1 year, complete data of 103 subjects (50 intervention and 53 control subjects) were obtained.

RESULTS—Lifestyle intervention reduced plasma leptin concentrations (–14.2%) in IGT subjects but did not alter plasma adiponectin (–0.3%) or resistin (–6.5%) concentrations despite marked improvements in glucose tolerance and insulin resistance.

CONCLUSIONS—Changes in leptin concentration were related to improvements in insulin sensitivity independent of changes in body composition.

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance • SLIM, Study on Lifestyle intervention and Impaired glucose tolerance Maastricht


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
Adipokines produced by adipose tissue, such as adiponectin, resistin, and leptin, may link obesity to insulin resistance, impaired glucose metabolism, and type 2 diabetes (1). Cross-sectional evidence for an association between insulin resistance and inflammation profile is ample (2). Nevertheless, the reported effects of lifestyle intervention on adipokines are limited and inconclusive (3,4). The first aim of the present study was to investigate whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes. Second, we investigated the potential of leptin, adiponectin, and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance. We addressed these aims in the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM).


   RESEARCH DESIGN AND METHODS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
Study design, inclusion and exclusion criteria, and the diet and exercise program of SLIM, an ongoing, randomized, controlled trial, have previously been described in detail (5,6). Each year, anthropometry, body fat percentage (7), physical fitness (VO2max), and plasma metabolites during fasting and 2 h after a 75-g oral glucose load are determined. The study protocol was approved by the local medical ethical committee of the Maastricht University. All subjects gave written informed consent.

Fasting plasma adiponectin (full length and globular, coefficient of variation [CV] 6.2%), resistin (homodimeric, CV 4.0%), and leptin (CV 5.8%) were simultaneously analyzed with enzyme-linked immunosorbent assays (Biovendor, Heidelberg, Germany). Of the 147 subjects enrolled, 131 completed the first year. For regression analysis, 28 subjects were excluded because of missing values for dietary intake (n = 3), VO2max (n = 23), or both (n = 2). No differences were observed between the included and excluded subjects.

Repeated-measures ANOVA were used for differences between groups over time. A two-tailed P value <0.05 was considered statistically significant. Data are presented as means ± SEM or, if not normally distributed (insulin, leptin, and adiponectin), as median (25th–75th percentile).


   RESULTS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
Lifestyle intervention was effective to improve glucose tolerance and insulin sensitivity, as shown by an improved 2-h glucose concentration (control group 0.36 ± 0.3 mmol/l and intervention group –0.78 ± 0.2 mmol/l; P < 0.001) and a reduced 2-h insulin response (1-year change 9.9 mU/l [–22.8 to 33.1] for the control group and –15.8 mU/l [–33.2 to 10.0] for the intervention group; P < 0.01). Adherence to the intervention was demonstrated by reduced body weight (–3%; P = 0.003) and BMI (–3%; P < 0.001) and increased physical fitness (VO2max + 5.6%; P < 0.001) after 1 year, as previously described (8). Leptin concentrations were reduced by –14.2% in the intervention group (baseline 16.7 ng/ml [6.4–27.2] and 1-year change –2.37 ng/ml [–5.5 to –0.3]) compared with the 0.5% increase in control subjects (baseline 11.6 ng/ml [5.9–24.8] and 1-year change 0.06 ng/ml [–2.2 to 1.5]; P < 0.01). No effects were observed on adiponectin for the intervention group (baseline 12.6 µg/ml [8.6–19.6] and 1-year change –0.06 µg/ml [–1.4 to 1.1]; –0.3%) or control group (baseline 14.1 µg/ml [9.3–19.3] and 1-year change –0.03 µg/ml [–1.0 to 1.2]; –0.2%). Also, in subjects with the highest body weight loss (>5%, n = 18), adiponectin concentrations did not change ({Delta}adiponectin –0.1 µg/ml [–0.7 to 3.8]; P = 0.43). Observations were similar for resistin in intervention (baseline 3.69 ± 0.21 µg/ml and 1-year change –0.24 ± 0.11 µg/ml; –6.5%) and control (baseline 3.67 ± 0.21 µg/ml and 1-year change –0.06 ± –0.07 µg/ml; –1.6%) subjects.

In the intervention group, leptin changes were positively associated with changes in body weight, BMI, body fat percentage, waist circumference, fasting glucose, 2-h glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, and plasma triglycerides (all Pearson correlation coefficients >0.48; all P values <0.001). Regression analyses in the intervention group revealed that the associations with fasting insulin, HOMA-IR, and 2-h glucose were less strong after adjustment for age, sex, lifestyle factors, and body composition but remained highly significant (Table 1). After full adjustment (Table 1, model 3), a decrease in HOMA-IR of 10% corresponds with a decrease in leptin concentrations of 3.9%. Changes in adiponectin or resistin were not significantly associated with changes in parameters under investigation, although after full adjustment in the regression analysis (model 3), a 1-unit (1%) decrease in A1C was related to a 15.6% increase in adiponectin concentration.


View this table:
[in this window]
[in a new window]

  		Table 1— β-Coefficients of changes in adiponectin and leptin concentrations after 1 year related to changes in metabolic parameters adjusted for age, sex, changes in lifestyle factors, and body composition in intervention subjects

 

   CONCLUSIONS—
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
The lifestyle intervention–induced decrease in leptin was strongly associated with a decrease in insulin resistance, and this association with insulin resistance was only partially explained by a reduction in body fat percentage. This is consistent with evidence that exercise may decrease circulating leptin concentration, independent of body composition (9). The decrease in circulating leptin may be explained by increased leptin sensitivity (10) with an effect on leptin production and clearance by feedback mechanisms. Leptin may also have peripheral effects on insulin signaling (12). Since most body weight was lost in the first 3 months and since weight loss in the last one-half year was only minor (–0.68 kg), it does not seem likely that leptin concentrations were reduced as a result of a catabolic state.

In the present study, adiponectin concentrations were not clearly altered by lifestyle changes. This was unexpected, since (extreme) weight reduction in obese individuals (~10–57 kg) was convincingly associated with an increase in plasma adiponectin concentrations ranging from 2.1 to 9.2 µg/ml (13–16). Our findings are supported, however, by other studies using lifestyle intervention programs according to general guidelines that failed to show an effect on adiponectin in diabetic (17) and obese (18) subjects. Although the molecular form of adiponectin may be of importance, peripheral insulin resistance has not been associated with a specific form of adiponectin thus far (4,18–20). The effect of weight loss on adiponectin concentrations seems to depend on the amount of weight loss and on the way in which weight loss was achieved.

This study shows that lifestyle intervention reduces plasma leptin concentrations in subjects with IGT but does not seem to alter plasma adiponectin or resistin concentrations despite marked improvements in glucose tolerance and insulin resistance. Leptin can be a biomarker for improvements in insulin sensitivity and glucose tolerance after lifestyle intervention, independent of changes in body composition.


   Acknowledgments
 
This study was supported by grants from the Dutch Diabetes Research Foundation (DFN 98.901 and DFN 2000.00.020) and the Netherlands Organization for Scientific Research (ZonMW 940-35-034, 2,200.0139).

We thank Jos Stegen, Hans Cremers, Tanja Hermans-Limpens, Ilse Nijs, and Marja Ockeloen.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 21 September 2007. DOI: 10.2337/dc07-0457.

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

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication March 7, 2007. Accepted for publication September 14, 2007.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

  1. Arner P: Insulin resistance in type 2 diabetes: role of the adipokines. Curr Mol Med 5:333–339, 2005[Medline]
  2. Duncan BB, Schmidt MI: The epidemiology of low-grade chronic systemic inflammation and type 2 diabetes. Diabetes Technol Ther 8:7–17, 2006[Medline]
  3. Monzillo LU, Hamdy O, Horton ES, Ledbury S, Mullooly C, Jarema C, Porter S, Ovalle K, Moussa A, Mantzoros CS: Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 11:1048–1054, 2003[Medline]
  4. Bluher M, Brennan AM, Kelesidis T, Kratzsch J, Fasshauer M, Kralisch S, Williams CJ, Mantzoros CS: Total and high–molecular weight adiponectin in relation to metabolic variables at baseline and in response to an exercise treatment program: comparative evaluation of three assays. Diabetes Care 30:280–285, 2007[Abstract/Free Full Text]
  5. Mensink M, Blaak EE, Corpeleijn E, Saris WH, de Bruin TW, Feskens EJ: Lifestyle intervention according to general recommendations improves glucose tolerance. Obes Res 11:1588–1596, 2003[Medline]
  6. Mensink M, Corpeleijn E, Feskens EJ, Kruijshoop M, Saris WH, de Bruin TW, Blaak EE: Study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM): design and screening results. Diabetes Res Clin Pract 61:49–58, 2003[Medline]
  7. Durnin JV, Womersley J: Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 32:77–97, 1974[Medline]
  8. Corpeleijn E, Feskens EJ, Jansen EH, Mensink M, Saris WH, de Bruin TW, Blaak EE: Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study. Diabetologia 49:2392–2401, 2006[Medline]
  9. Pasman WJ, Westerterp-Plantenga MS, Saris WH: The effect of exercise training on leptin levels in obese males. Am J Physiol 274:E280–E286, 1998[Medline]
  10. Montez JM, Soukas A, Asilmaz E, Fayzikhodjaeva G, Fantuzzi G, Friedman JM: Acute leptin deficiency, leptin resistance, and the physiologic response to leptin withdrawal. Proc Natl Acad Sci U S A 102:2537–2542, 2005[Abstract/Free Full Text]
  11. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ: Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 283:E187–E192, 2002[Abstract/Free Full Text]
  12. Fruhbeck G: Intracellular signalling pathways activated by leptin. Biochem J 393:7–20, 2006[Medline]
  13. Lazzer S, Vermorel M, Montaurier C, Meyer M, Boirie Y: Changes in adipocyte hormones and lipid oxidation associated with weight loss and regain in severely obese adolescents. Int J Obes (Lond) 29:1184–1191, 2005[Medline]
  14. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, Chen CL, Tai TY, Chuang LM: Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819, 2001[Abstract/Free Full Text]
  15. Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz CA, Sinha MK, Pories WJ, MacDonald KG, Dohm GL: Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 283:E861–E865, 2002[Abstract/Free Full Text]
  16. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D: Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289:1799–1804, 2003[Abstract/Free Full Text]
  17. Aas AM, Seljeflot I, Torjesen PA, Diep LM, Thorsby PM, Birkeland KI: Blood glucose lowering by means of lifestyle intervention has different effects on adipokines as compared with insulin treatment in subjects with type 2 diabetes. Diabetologia 49:872–880, 2006[Medline]
  18. Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO, Mohlig M, Pfeiffer AF, Spranger J: Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes 54:2712–2719, 2005[Medline]
  19. Abbasi F, Chang SA, Chu JW, Ciaraldi TP, Lamendola C, McLaughlin T, Reaven GM, Reaven PD: Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes. Am J Physiol Regul Integr Comp Physiol 290:R139–R144, 2006[Abstract/Free Full Text]
  20. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F, Froguel P, Kimura S, Nagai R, Kadowaki T: Impaired multimerization of human adiponectin mutants associated with diabetes: molecular structure and multimer formation of adiponectin. J Biol Chem 278:40352–40363, 2003[Abstract/Free Full Text]
  21. Page ST, Herbst KL, Amory JK, Coviello AD, Anawalt BD, Matsumoto AM, Bremner WJ: Testosterone administration suppresses adiponectin levels in men. J Androl 26:85–92, 2005[Abstract/Free Full Text]
  22. Chevillotte E, Giralt M, Miroux B, Ricquier D, Villarroya F: Uncoupling protein-2 controls adiponectin gene expression in adipose tissue through the modulation of reactive oxygen species production. Diabetes 56:1042–1050, 2007[Medline]
  23. Rubin D, Helwig U, Nothnagel M, Lemke N, Schreiber S, Folsch UR, Doring F, Schrezenmeir J: Postprandial plasma adiponectin decreases after glucose and high fat meal and is independently associated with postprandial triacylglycerols but not with - 11388 promoter polymorphism. Br J Nutr. 30 July 2007 [Epub ahead of print]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc07-0457v1
30/12/3125    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Corpeleijn, E.
Right arrow Articles by Blaak, E. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Corpeleijn, E.
Right arrow Articles by Blaak, E. E.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum