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Exercise Training Lowers Plasma Visfatin Concentrations in Patients with Type 1 Diabetes

Departments of Clinical Pharmacology (D.G.H., J.P., M.M., M.W.), Physical Medicine and Rehabilitation (G.F.W.), and Department of Internal Medicine III, Division of Endocrinology and Metabolism (M.W.), Medical University of Vienna, 1090 Vienna, Austria; and Rehabilitationszentrum für Diabetes der PVA (M.F.), 2534 Alland, Austria

Address all correspondence and requests for reprints to: Dr. Michael Wolzt, Medical University of Vienna, Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria. E-mail: michael.wolzt{at}meduniwien.ac.at.

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Context: Exercise training exerts beneficial effects on metabolic and vascular risk factors in patients with type 1 diabetes mellitus (T1DM). It is unknown whether training also influences concentrations of visfatin, a novel insulin-mimetic adipocytokine.

Objectives: In this study, we have investigated whether plasma visfatin concentrations are altered by training in patients with T1DM.

Design and Patients: Fasting plasma visfatin concentrations and metabolic parameters were measured in 18 patients with T1DM who participated in a supervised aerobic exercise program for 4 months. Three subjects discontinued training prematurely after 2 months. Samples were obtained before and during training and 8 months after the end of regular exercise. Fourteen healthy young subjects served as controls.

Results: At baseline, patients with T1DM had higher visfatin concentrations than controls (64.1 ± 12.0 vs. 1.3 ± 0.0 ng/ml, P < 0.01). Exercise reduced visfatin after 2 and 4 months to 27.8 ± 2.6 (n = 18) and 17.5 ± 3.4 ng/ml (n = 15), respectively (P < 0.001 for n = 15 subjects who participated in all visits, ANOVA). This effect was maintained 8 months after cessation of training, with visfatin concentrations of 19.7 ± 5.0 ng/ml (n = 15). Metabolic parameters were not affected by the training program.

Conclusion: Elevated visfatin concentrations in patients with T1DM can be lowered by regular physical exercise. It is unknown whether glucose tolerance is affected by changes in visfatin concentrations.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion References

 
THE INSULIN-MIMETIC adipocytokine visfatin is produced and secreted by fat tissue and other cells such as macrophages (1, 2). Increased plasma visfatin concentrations are observed in patients with diabetes mellitus type 2 (3) and gestational diabetes (4) and can be lowered in obese subjects by weight loss (5).

Aerobic exercise training exerts salutary effects in subjects with type 1 or type 2 diabetes on the glycemic profile and influences vascular and metabolic cardiovascular risk factors including insulin resistance (6, 7). However, the effect of training on circulating adipocytokines is not consistent. Different results have been obtained where leptin has been shown to decrease in some studies (8, 9, 10) but not in others (11, 12, 13, 14). Likewise, adiponectin concentrations remain unaltered (15), increased (16, 17, 18, 19), or decreased (20) after training. Exercise-induced changes in visfatin concentrations, which may affect insulin sensitivity (1), have not been described yet.

Therefore, we have assessed the effects of training on plasma visfatin concentrations and compared the effects with those of untrained healthy control subjects.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion References

 
Venous blood samples from patients included in a training study (21) were used for this trial. The study was approved by the Ethics Committee of the University of Vienna and complied with the Declaration of Helsinki, including current revisions and the Good Clinical Practice guidelines. Written informed consent was obtained from all study participants before enrollment.

Patients

Eighteen patients (11 women and seven men, aged 42 ± 10 yr) with type 1 diabetes mellitus (T1DM) were included in this longitudinal study (Table 1). Fourteen healthy controls (seven women and seven men, aged 29 ± 5 yr) who were not matched with the intervention group for age or sex, who had a body mass index (BMI) of less than 25 kg/m², and who did not exercise regularly and did not participate in the training program, served as controls and were examined once.

Study protocol

Subjects were supervised in a 4-month training program of stationary cycling. Each exercise session lasted for 1 h, and workloads were slowly increased on an individual basis until a heart rate of 60–70% of the previously established difference from resting to maximum heart rate was achieved. During the first 2 wk, training took place twice a week, and during the remaining study period, three times a week. The patients were allowed to carry out an additional training program at home, but compliance with the supervised training sessions had to be more than 60% for study eligibility. Three subjects discontinued the study after 2 months of training due to lack of time required. Fasting blood samples for assessment of laboratory parameters were collected from 18 patients with T1DM group before and after 2 months, and from remaining 15 patients after 4 months of the training program and 8 months after the end of training.

Determination of visfatin

Plasma samples were stored at –70 C until analysis. Visfatin was analyzed using commercially available ELISA kit (Phoenix Peptides, Karlsruhe, Germany) with an interassay and intraassay coefficient of variation of less than 6%.

Statistical analysis

All data sets were tested for normal distribution using the Kolmogorov-Smirnov test. Baseline measurements were compared between groups using the Mann-Whitney U test. The effects of training were assessed by one-way ANOVA (Friedman-ANOVA) and the Wilcoxon signed-rank test within the group of 15 subjects who participated in all visits, respectively. All calculations were performed using the Statistica software package (release 4.5; StatSoft, Tulsa, OK). P < 0.05 was considered significant. Values are expressed as means ± SD unless indicated otherwise.

	Results

Top Abstract Introduction Patients and Methods Results Discussion References

 
At baseline, patients with T1DM were older, had higher fasting blood glucose concentrations, and had elevated circulating visfatin concentrations compared with controls (all P < 0.05, Table 1).

Plasma visfatin concentrations were also elevated in a subgroup of eight young patients with T1DM (age 33 ± 2 yr) with 66.5 ± 15.5 ng/ml (P < 0.01 vs. controls). Furthermore, the three patients with T1DM who discontinued training after 2 months had similar BMI (28.5 ± 5.2 kg/m²), total cholesterol (227 ± 75 mg/dl), triglyceride (98 ± 69 mg/dl), and visfatin plasma concentrations (57.8 ± 12.6 ng/ml) as those who completed the study. There was no correlation between visfatin and BMI or age at baseline in patients with T1DM, controls, or in a pooled analysis.

After 2 and 4 months of training, visfatin concentrations were significantly reduced in patients with T1DM (P < 0.001 vs. baseline, ANOVA; Fig. 1 and Table 1). Eight months after discontinuation of regular exercise, this effect was maintained and visfatin concentrations were still lower than before training (P < 0.01, Table 1). In contrast to visfatin, BMI, fasting glucose concentrations, glycosylated hemoglobin, and the lipid profile were not changed during training or 8 months later in T1DM (Table 1).

View larger version (19K): [in this window] [in a new window]   FIG. 1. Individual visfatin plasma concentrations at baseline and after 2 and 4 months of exercise in patients with T1DM.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

Increased plasma visfatin concentrations have been described previously in patients with type 2 diabetes and have been associated with the disease (2, 3). The present finding of similarly elevated visfatin, as also found in obesity (5), does not support the concept that visfatin may play a specific role in the pathogenesis of the metabolic syndrome because T1DM originates from different pathophysiology. Furthermore, visfatin was substantially higher in lean T1DM patients than in controls. Thus, elevated plasma visfatin may be a consequence of intermittent or continued hyperglycemia or lack of physiological insulin exposure and may represent a feedback mechanism of glucose homeostasis. Indeed, an acute regulation of visfatin by glucose and insulin has already been demonstrated in vivo in healthy subjects and in isolated adipocytes (22). The acute effect of exogenous hyperglycemia in healthy subjects is comparatively small and, therefore, effects on visfatin plasma concentrations are unlikely related to increased fasting glucose concentrations in T1DM. Likewise, BMI or age had no influence on circulating visfatin concentrations, arguing against a confounding influence of these parameters in the present study. Consistently, the finding that effects of training on visfatin were seen in the absence of changes in glucose metabolism or lipid profile suggest a different regulation of visfatin metabolism by chronic exercise.

In our study, low concentrations of visfatin were detectable in healthy controls, which is comparable to previous reports (22). Visfatin plasma concentrations in T1DM were in the range of those of patients with type 2 diabetes. However, the implications of lower visfatin concentrations as induced by training are unclear. It might be speculated that continuous stimulation of tissue insulin receptors by visfatin might influence insulin sensitivity adversely and, therefore, that lowering of the insulin-mimetic adipocytokine could contribute to improved glucose tolerance as demonstrated in some training studies. However, training did not normalize plasma visfatin, and the agonistic properties of visfatin on the insulin receptor are not fully characterized yet.

The decrease of visfatin after 2 and 4 months of exercise suggests that other factors than glucose metabolism, body weight, or the lipid profile may be responsible for this finding. The sustained effect of training 8 months after cessation indicates that altered visfatin production, secretion, or metabolism has been induced by exercise, unlike the transient effects seen on vascular function (21). These mechanisms cannot be derived from the present study.

In summary, circulating visfatin concentrations are increased in patients with T1DM and are reduced by chronic exercise. Additionally, this effect is maintained after training cessation.

	Footnotes

 
The authors state that they have no conflict of interest.

First Published Online August 8, 2006

Abbreviations: BMI, Body mass index; T1DM, type 1 diabetes mellitus.

Received May 10, 2006.

Accepted August 2, 2006.

	References

Top Abstract Introduction Patients and Methods Results Discussion References

 

1. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I 2005 Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430[Abstract/Free Full Text]
2. Berndt J, Klöting N, Kralisch S, Kovacs P, Fasshauer M, Schön MR, Stumvoll M, Blüher M 2005 Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 54:2911–2916[Abstract/Free Full Text]
3. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ 2006 Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 91:295–299[Abstract/Free Full Text]
4. Krzyzanowska K, Krugluger W, Mittermayer F, Rahman R, Haider D, Shnawa N, Schernthaner G 2006 Increased visfatin concentrations in women with gestational diabetes mellitus. Clin Sci (Lond) 110:605–609[Medline]
5. Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B 2006 Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab 91:1578–1581[Abstract/Free Full Text]
6. Lehmann R, Kaplan V, Bingisser R, Bloch KE, Spinas GA 1997 Impact of physical activity on cardiovascular risk factors in IDDM. Diabetes Care 20:1603–1611[Abstract]
7. Yokoyama H, Emoto M, Araki T, Fujiwara S, Motoyama K, Morioka T, Koyama H, Shoji T, Okuno Y, Nishizawa Y 2004 Effect of aerobic exercise on plasma adiponectin levels and insulin resistance in type 2 diabetes. Diabetes Care 27:1756–1758[Free Full Text]
8. Ishii T, Yamakita T, Yamagami K, Yamamoto T, Miyamoto M, Kawasaki K, Hosoi M, Yoshioka K, Sato T, Tanaka S, Fujii S 2001 Effect of exercise training on serum leptin levels in type 2 diabetic patients. Metabolism 50:1136–1140[CrossRef][Medline]
9. Hickey MS, Houmard JA, Considine RV, Tyndall GL, Midgette JB, Gavigan KE, Weidner ML, McCammon MR, Israel RG, Caro JF 1996 Gender-dependent effects of exercise training on serum leptin levels in humans. Am J Physiol 272:E562–E566
10. Pasman WJ, Westerterp-Plantenga MS, Saris WHM 1998 The effect of exercise training on leptin levels in obese males. Am J Physiol 274:E280–E286
11. Kohrt WM, Landt M, Birge SJ 1996 Serum leptin levels are reduced in response to exercise training, but not hormone replacement therapy, in older women. J Clin Endocrinol Metab 81:3980–3985[Abstract/Free Full Text]
12. Perusse L, Collier G, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Nadeau A, Zimmet PZ, Bouchard C 1997 Acute and chronic effects of exercise on leptin levels in humans. J Appl Physiol 83:5–10[Abstract/Free Full Text]
13. Noland RC, Baker JT, Boudreau SR, Kobe RW, Tanner CJ, Hickner RC, McCammon MR, Houmard JA 2001 Effect of intense training on plasma leptin in male and female swimmers. Med Sci Sports Exerc 33:227–231
14. Desgorces FD, Chennaoui M, Gomez-Merino D, Drogou C, Guezennec CH 2004 Leptin response to acute prolonged exercise after training in rowers. Eur J Appl Physiol 91:677–681[Medline]
15. Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz S, Sinha MK, Pories WJ, MacDonald KG, Dohm GL 2002 Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol 283:E861–E865
16. Hotta K, Funahashi Y, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y 2000 Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscl Thromb Vasc Biol 20:1595–1599[Abstract/Free Full Text]
17. Kriketos AD, Gan SK, Pounten AM, Furler SM, Chisholm DJ, Campbell LV 2004 Exercise increases adiponectin levels and insulin sensitivity in humans. Diabetes Care 27:629–630[Free Full Text]
18. Takanami Y, Kawai Y, Kinoshita F, Mobara O, Shimomitsu T 2002 Aerobic exercise training increases an adipocyte-derived anti-diabetic, anti-atherogenic protein, adiponectin. Diabetes 51(Suppl 2):A61
19. Ishii T, Yamakita T, Yamaguchi K, Fukumoto M, Yoshioka K, Hosoi M, Sato T, Tanaka S, Fujii S 2002 Plasma adiponectin levels are associated with insulin sensitivity improved by exercise training in type 2 diabetic patients. Diabetes 51(Suppl 2):A248
20. Yatagai T, Nishida Y, Nagasaka S, Nakamura T, Tokuyama K, Shindo M, Tanaka H, Ishibashi S 2003 Relationship between exercise training-induced increase in insulin sensitivity and adiponectinemia in healthy men. Endocr J 50:233–238[CrossRef][Medline]
21. Fuchsjäger-Mayrl G, Pleiner J, Wiesinger GF, Sieder AE, Quittan M, Nuhr MJ, Francesconi C, Seit HP, Francesconi M, Schmetterer L, Wolzt M 2002 Exercise training improves vascular endothelial function in patients with type 1 diabetes. Diabetes Care 25:1795–1801[Abstract/Free Full Text]
22. Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M 2006 The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia 49:1909–1914[CrossRef][Medline]

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This Article Abstract Full Text (PDF) All Versions of this Article: 91/11/4702    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haider, D. G. Articles by Wolzt, M. Search for Related Content PubMed PubMed Citation Articles by Haider, D. G. Articles by Wolzt, M. Related Collections Diabetes and Insulin Metabolism