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


     

Published online April 6, 2007
Diabetes Care 30:1889-1891, 2007
DOI: 10.2337/dc07-0013
© 2007 by the American Diabetes Association
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc07-0013v1
30/7/1889    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 Haider, D. G.
Right arrow Articles by Kautzky-Willer, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haider, D. G.
Right arrow Articles by Kautzky-Willer, A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Pathophysiology/Complications
Brief Report

Visfatin Response to Glucose Is Reduced in Women With Gestational Diabetes Mellitus

Dominik G. Haider, MD1,2, Ammon Handisurya, MD2, Angela Storka, MD1, Elena Vojtassakova1, Anton Luger, MD2, Giovanni Pacini, DSC3, Andrea Tura, PHD3, Michael Wolzt, MD1,2 and Alexandra Kautzky-Willer, MD2

1 Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
2 Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria
3 Metabolic Unit, Institute of Biomedical Engineering, Padova, Italy

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

Abbreviations: GDM, gestational diabetes mellitus • OGTT, oral glucose tolerance test


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
The insulin-mimetic adipocytokine visfatin has been associated with insulin resistance in some studies and is regulated by glucose. We hypothesized that glucose-induced changes in plasma visfatin are different in women with gestational diabetes mellitus (GDM). Plasma visfatin concentrations were studied in 10 women with GDM and 10 age-matched healthy women, in pregnancy weeks 24–28, during a standard oral glucose tolerance test (OGTT). Women with GDM had lower systemic visfatin concentrations than control subjects (1.9 ± 0.8 vs. 5.2 ± 4.4 ng/ml, respectively, P < 0.05), which were associated with fasting glucose (P < 0.05). The glucose-induced increase in visfatin over baseline was smaller in women with GDM, with an area under the curve of 409 ± 106 vs. 780 ± 345 ng · ml–1 · min–1 in control subjects (P < 0.05). Reduced glucose-induced increases in circulating visfatin may be associated with impaired glucose tolerance in women with GDM.

Women with GDM are at increased risk for developing type 2 diabetes; however, the pathophysiology is still poorly understood. Nonetheless, a variety of abnormalities that are also found in patients with type 2 diabetes are seen early in women in GDM (1). Among the factors that might contribute to altered glucose handling are changes in adipocytokines. For example, plasma adiponectin concentrations are lowered (2), and leptin and resistin persistently increased after delivery in women with GDM and are associated with hyperglycemia and insulin resistance (3,4).

The adipocytokine visfatin has been reported to mimic actions of insulin by activating the insulin signal transduction pathway through binding to the same receptor (5). Systemic visfatin concentrations are acutely regulated by glucose and insulin (6) and elevated in patients with insulin resistance, obesity, and diabetes, as well as by rosiglitazone treatment (7–11).

In an effort to address the question whether plasma visfatin regulation is altered in women with GDM, we have studied its concentration during pregnancy weeks 24–28 and compared it with that of matched healthy pregnant women during a standard OGTT.


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
Ten women with GDM (aged 33 ± 2 years) diagnosed during pregnancy weeks 24–28 were invited to participate in the study. GDM was defined as two or more of the following criteria: fasting morning plasma glucose after a minimum of 3 days of unrestricted diet and unlimited physical activity ≥5.3 mmol/l, 1-h postload 75-g glucose value ≥10.0 mmol/l, or 2-h postload glucose value ≥8.6 mmol/l. As control subjects, age-matched (34 ± 1 years) pregnant women with normal OGTT were included.

Inclusion criteria were signed informed consent, absence of a clinically relevant illness, normal findings in the medical history and physical examination except for GDM, and normal laboratory values. Subjects were excluded if any clinically relevant abnormality was found as part of the screening or in any of the laboratory tests including circulating anti-insulin antibodies and anti-islet cell antibodies. No subject was on a special diet or reported intake of any medication, including "over-the-counter" drugs, at the time of blood sampling.

Study protocol
Venous blood samples for measurement of lipid status, glucose, insulin, and visfatin concentrations were taken 1 h before a standard 75-g OGTT and was carried out after overnight fasting. Venous blood sampling was repeated 30, 60, and 120 min after an oral glucose load. Insulin sensitivity during an OGTT was assessed by the oral glucose insulin sensitivity index, which describes glucose clearance (12). Standard laboratory parameters were quantified according to certified routine methods at the Clinical Institute for Medical and Chemical Laboratory Diagnostics, Allgemeines Krankenhaus Wien.

Measurement of visfatin
Plasma samples were stored at –70°C until analysis. Visfatin was analyzed using a commercially available enzyme-linked immunosorbent assay kit (Phoenix Peptides, Karlsruhe, Germany), with an inter- and intra-assay coefficient of variation <6%.

Statistical analysis
All datasets were tested for normal distribution using the Kolmogorov-Smirnov test. Changes over baseline were assessed from the areas under the concentration versus time curves. Differences between groups were compared using the Mann-Whitney U test. Effects of OGTT were assessed by repeated-measures ANOVA. All calculations were performed using the Statistica software package (release 4.5; StatSoft, Tulsa, OK). P < 0.05 was considered significant. Data are expressed as means ± SD, unless otherwise indicated.


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
Groups of pregnant women were comparable regarding age, BMI, and anthropometric and metabolic parameters, except for higher fasting plasma glucose concentrations (5.4 ± 0.6 vs. 4.2 ± 0.7 mmol/l, P < 0.05) and lower oral glucose insulin sensitivity index values (376.5 ± 21.1 vs. 493.4 ± 37.1 ml/min per m2, P < 0.05) in women with GDM. Fasting plasma visfatin concentrations were lower in women with GDM (Fig. 1) and increased between 0.6–3.8 and 0.6–7.1 ng/ml in women with GDM and control subjects, respectively.


Figure 1
View larger version (8K):
[in this window]
[in a new window]

  		Figure 1— Plasma concentrations of visfatin (A), glucose (B), and insulin (C) during an OGTT in women with GDM ({circ}) and age-matched healthy pregnant control subjects ({blacksquare}). Data are means ± SE. +P < 0.05 vs. baseline (repeated-measures ANOVA).

 
The glucose-induced change in visfatin over baseline as calculated by the area under the curve was 409 ± 106 ng · ml–1 · min–1 in GDM and 780 ± 345 ng · ml–1 · min–1 in control subjects (P < 0.05 between groups, Mann-Whitney U test). A significant correlation was detectable between fasting glucose and visfatin concentrations in both groups (r = 0.46, P < 0.05 in GDM and r = 0.45, P < 0.05 in control subjects) but not among other parameters.


   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
This study demonstrates that a glucose-induced visfatin increase is blunted in women with GDM, who also have lower fasting plasma concentrations compared with age-matched pregnant women. This finding extends previous studies from different populations with GDM, where increased (13) or decreased (14) circulating visfatin concentrations have been reported. The discrepancy of these finding is unclear but may be related to differences regarding sampling time during pregnancy. The present data nevertheless confirm the regulatory role of glucose on circulating visfatin levels, which is consistent with results obtained during hyperglycemic clamp studies in healthy young men (6).

The cause of reduced fasting visfatin and mitigated response to glucose challenge in women with GDM is not directly accessible from this study. It has been demonstrated that plasma visfatin concentrations are inversely correlated to progressive ß-cell deterioration in patients with type 1 or type 2 diabetes (15). The present data argue against an assumption that altered pancreatic insulin secretion has contributed to reduced plasma visfatin in GDM because insulin plasma concentrations were comparable in fasting conditions. This is important, as insulin is known to suppress glucose-induced visfatin release in vitro and in vivo (6). Further, glucose-induced insulin release was similar in women with GDM as in healthy control subjects 60 min after an oral glucose load.

On the contrary, as it is known that glucose induces visfatin release, which is also a consistent finding in this study, one might have expected higher visfatin concentrations in women with GDM. Thus, factors other than glucose and insulin alone seem to influence the regulation of visfatin in pregnancy, such as proinflammatory cytokines (2). Indeed, an association between plasma tumor necrosis factor-{alpha} and visfatin mRNA in subcutaneous adipose tissue has recently been reported (16). It is unclear if differences in fasting or glucose-stimulated plasma visfatin can be regarded as compensatory mechanisms to maintain glucose homeostasis in GDM.

In summary, GDM is associated with lower visfatin concentrations than that found in healthy women during pregnancy. Visfatin is transiently increased after an oral gucose load, but this response is mitigated in GDM.


   Acknowledgments
 
We thank Veronika Ponzauner, RN, for assistance with sampling and logistics.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 30 March 2007. DOI: 10.2337/dc07-0013.

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 January 4, 2007. Accepted for publication March 22, 2007.


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

  1. Buchanan TA, Xiang AH: Gestational diabetes mellitus. J Clin Invest 115:485–491, 2005[Medline]
  2. Winzer C, Wagner O, Festa A, Schneider B, Roden M, Bancher-Todesca D, Pacini G, Funahashi T, Kautzky-Willer A: Plasma adiponectin, insulin sensitivity, and subclinical inflammation in women with prior gestational diabetes mellitus. Diabetes Care 27:1721–1727, 2004[Abstract/Free Full Text]
  3. Kautzky-Willer A, Prager R, Ludvik B, Pacini G, Tura A, Bieglmeyer C, Schneider B, Waldhäusl W: Increased plasma leptin in gestational diabetes. Diabetologia 44:164–172, 2001[Medline]
  4. Lappas M, Yee K, Permezel M, Rice GE: Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies. J Endocrinol 186:457–465, 2005[Abstract/Free Full Text]
  5. 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: Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430, 2005[Abstract/Free Full Text]
  6. Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M: The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia 49:1909–1914, 2006[Medline]
  7. Haider DG, Pleiner J, Francesconi M, Wiesinger GF, Müller M, Wolzt M: Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes. J Clin Endocrinol Metab 91:4702–4704, 2006[Abstract/Free Full Text]
  8. Haider DG, Mittermayer F, Schaller G, Artwohl M, Baumgartner-Parzer SM, Prager G, Roden M, Wolzt M: Free fatty acids normalize a rosiglitazone-induced visfatin release. Am J Physiol Endocrinol Metab 291:E885–E890, 2006[Abstract/Free Full Text]
  9. Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B: Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab 91:1578–1581, 2006[Abstract/Free Full Text]
  10. Haider DG, Schindler K, Mittermayer F, Müller M, Nowotny P, Rieger A, Luger A, Ludvik B, Wolzt M: Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma concentrations in HIV-positive patients. Clin Pharmacol Ther 81:580–585, 2007[Medline]
  11. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ: 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, 2006[Abstract/Free Full Text]
  12. Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ: A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548, 2001[Abstract/Free Full Text]
  13. Krzyzanowska K, Krugluger W, Mittermayer F, Rahman R, Haider D, Shnawa N, Schernthaner G: Increased visfatin concentrations in women with gestational diabetes mellitus. Clin Sci (Lond) 110:605–609, 2006[Medline]
  14. Chan TF, Chen YL, Lee CH, Chou FH, Wu LC, Jong SB, Tsai EM: Decreased plasma visfatin concentrations in women with gestational diabetes mellitus. J Soc Gynecol Investig 13:364–367, 2006[Medline]
  15. Lopez-Bermejo A, Chico-Julia B, Fernandez-Balsells M, Recasens M, Esteve E, Casamitjana R, Ricart W, Fernandez-Real JM: Serum visfatin increases with progressive ß-cell deterioration. Diabetes 55:2871–2875, 2006[Abstract/Free Full Text]
  16. Varma V, Yao-Borengasser A, Rasouli N, Bodles AM, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer HJ 3rd, McGehee RE Jr, Fried SK, Kern PA: Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids and inflammation. J Clin Endocrinol Metab 92:666–672, 2007[Abstract/Free Full Text]

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 Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc07-0013v1
30/7/1889    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 Haider, D. G.
Right arrow Articles by Kautzky-Willer, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haider, D. G.
Right arrow Articles by Kautzky-Willer, A.
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