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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-1013
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The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4702-4704
Copyright © 2006 by The Endocrine Society

BRIEF REPORT

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

Dominik G. Haider, Johannes Pleiner, Mario Francesconi, Günther F. Wiesinger, Markus Müller and Michael Wolzt

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 1Go). 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.


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  		TABLE 1. BMI and laboratory parameters in patients with T1DM at baseline, after 2 and 4 months of training, and 8 months after the end of the training period

 
No participant had uncontrolled hypertension or signs of autonomic cardiac neuropathy. All patients were receiving basal bolus insulin treatment. One patient had microalbuminuria, four had signs of diabetic retinopathy, two were on calcium channel blocker, and two were on statin therapy, which was unchanged during the observation period. Cardiac and pulmonary dysfunction was excluded by transthoracic echocardiography and a lung-function test before the study begin.

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 1Go).

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. 1Go and Table 1Go). Eight months after discontinuation of regular exercise, this effect was maintained and visfatin concentrations were still lower than before training (P < 0.01, Table 1Go). 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 1Go).


Figure 1
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  		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
 
This study extends previous reports in subjects with impaired glucose tolerance to show that elevated visfatin plasma concentrations are also present in patients with T1DM. Furthermore, augmented visfatin concentrations are influenced by training, which causes a sustained reduction in plasma visfatin.

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
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 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

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