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

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.

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.

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%.

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.

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.

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.

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 β-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-α 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.

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