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© Borgis - Postępy Nauk Medycznych 1/2012, s. 67-71
*Wojciech Bik1, Agnieszka Baranowska-Bik2, Ewa Wolińska-Witort1, Małgorzata Kalisz1, Magdalena Białkowska3, Lidia Martyńska1, Bogusława Baranowska1
Osoczowe stężenia waspiny u kobiet z otyłością olbrzymią
Vaspin plasma levels in extremely obese women**
1Department of Neuroendocrinology, Medical Centre of Postgraduate Education, Warsaw
Head of Department: dr hab. med. Wojciech Bik
2Department of Endocrinology, Medical Centre of Postgraduate Education, Warsaw
Head of Department: prof. dr hab. med. Wojciech Zgliczyński
3National Food and Nutrition Institute, Warsaw
Head of Department: prof. dr hab. med. Mirosław Jarosz
Streszczenie
Wstęp. Pomimo iż otyłość związana jest z insulinoopornością, cukrzycą typu 2 i ryzykiem chorób układu sercowo-naczyniowego, tzw. otyli, metabolicznie zdrowi, nawet jeśli występuje otyłość olbrzymia, nie wykazują nasilonych zaburzeń gospodarki węglowodanowej i lipidowej. Waspina jest nową adipokiną, która może wpływać na regulację poziomów glukozy i insuliny.
Cel pracy. Celem pracy była ocena osoczowych stężeń waspiny u kobiet z otyłością olbrzymią w odniesieniu do obecności zespołu metabolicznego.
Materiał i metody. Badaniem objęto 55 Polek, wśród nich 26 z otyłością olbrzymią (BMI ≥ 40 kg/m2) i zespołem metabolicznym, 10 z otyłością olbrzymią bez zespołu metabolicznego oraz 19 zdrowych, szczupłych kobiet jako grupa kontrolna. Zespół metaboliczny rozpoznano zgodnie z kryteriami IDF 2005. U wszystkich badanych wykonano pomiary antropometryczne. Krew pobierano na czczo i oznaczano profil lipidowy i stężenie glukozy. Osoczowe stężenia insuliny i waspiny określano odpowiednio metodami IRMA i ELISA. Wyliczono wskaźnik HOMA-IR.
Wynik. Stężenia waspiny były znamiennie wyższe u kobiet z otyłością olbrzymią w porównaniu do grupy kontrolnej. Jednakże, nie wykazaliśmy istotnych różnić w poziomach waspiny pomiędzy podgrupami otyłych pacjentek. Najbardziej zaburzony profil lipidowy obserwowano u kobiet otyłych z zespołem metabolicznym. W tej grupie stwierdzono także najsilniej wyrażone nieprawidłowości gospodarki węglowodanowej z najwyższymi wartościami HOMA-IR. Stwierdzono istotne statystycznie korelacje pomiędzy wartościami waspiny a obwodem talii w grupie osób z otyłością olbrzymią.
Wnioski. Wyniki naszych badań wskazują, że wahania poziomów waspiny są zależne od wielu czynników, a nie tylko od wartości BMI, parametrów gospodarki węglowodanowej lub obecności zespołu metabolicznego. W grupie kobiet z otyłością olbrzymią wspina nie jest wskaźnikiem zaburzeń metabolicznych.
Summary
Introduction. Although obesity is associated with insulin resistance, type 2 diabetes and cardiovascular risk, ‘obese but metabolically healthy’ individuals, even when extremely obese, do not present disturbed glucose or lipid profiles. Vaspin is a novel adipokin that may influence glucose/insulin homeostasis.
Aim. We aimed to assess plasma vaspin levels in morbidly obese women and to correlate these results with the presence of metabolic syndrome.
Material and methods. The study included 55 Polish women among them 26 subjects had morbid obesity (BMI ≥ 40 kg/m2) with metabolic syndrome, 10 subjects were extremely obese without metabolic syndrome and 19 healthy, lean women served as a control group. Metabolic syndrome was diagnosed according to the criteria of IDF 2005. All subjects underwent anthropometric measurements. Fasting plasma glucose levels and lipid profiles were determined. Plasma insulin and vaspin levels were estimated using IRMA and ELISA, respectively. HOMA-IR was calculated.
Results. Plasma vaspin concentration was significantly higher in extremely obese women in comparison with the controls. However, we did not observe any noticeable differences in vaspin levels among two subgroups of morbidly obese subjects. The most disturbed lipid profile was seen in the group of obese subjects with metabolic syndrome. This group showed also heightened disturbances in carbohydrate metabolism with the highest HOMA-IR.
We identified that vaspin concentration significantly correlated with waist circumference in extremely obese women.
Conclusions. The results of our study indicate that circulating vaspin levels depend on several factors not only on BMI, glucose metabolism indicators or the presence of metabolic syndrome. In the group of morbidly obese individuals vaspin is not a marker of metabolic disturbances.
Introduction
The history of metabolic syndrome started in the 17th century when the first description of metabolic abnormalities was published by Nicolaes Tulp (1). However, the last century’s discoveries were the milestones in the studies on the role of metabolic disturbances. It is widely known that in 1988 Professor Gerald Reaven gave the definition of X syndrome (2) that was modified in the following years. But the studies on metabolic syndrome had begun earlier. Interestingly, in the 50s Polish scientist professor Jakub Węgierko presented the coexistence of diabetes with metabolic disturbances and several diseases including hypertension, obesity, cholelithiasis and atherosclerosis (3). Professor Węgierko provided also the definition of this particular type of diabetes and his definition is very similar to the one used nowadays for metabolic syndrome (4).
Despite the fact that the problem of metabolic syndrome has been thoroughly studied over last years and criteria have been changed several times up to date, there are still controversies concerning health implications of the presence of metabolic syndrome and its compounds (5).
Doubtless, obesity, especially when characterized with increased amount of abdominal visceral fat, is associated with insulin resistance, type 2 diabetes and cardiovascular risk (6). However, there is a group of obese individuals in whom metabolic abnormalities are not expressed. They do not present disturbed glucose or lipid profiles even in the presence of extreme obesity. This group is termed ‘obese but metabolically healthy’.
Many studies confirmed that adipose tissue is able to secrete biologically active substances named adipokines that may modulate glucose and lipid homeostasis, and influence immune system (7). Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a novel adipokine that was isolated for the first time from the visceral white adipose tissue of animal model of type 2 diabetes and visceral obesity (8). It is believed to possess insulin-sensitizing properties as it has been reported that administration of recombinant vaspin enhances insulin sensitivity in obese mice (8). Moreover, vaspin mRNA is found to be highly expressed in adipocytes from obese rats (8). However, data from human studies on the association between vaspin and obesity, metabolic syndrome and glucose homeostasis remain equivocal.
Thus, we aimed to assess plasma vaspin levels in morbidly obese women and to correlate these results with the presence of metabolic syndrome.
Material and methods
The study was carried out on 55 Polish descend women who were assigned to the following groups:
– 26 subjects with morbid obesity (BMI ≥ 40 kg/m2) with metabolic syndrome (aged 45.44 ± 12.04 yrs),
– 10 subjects with morbid obesity (BMI ≥ 40 kg/m2) without metabolic syndrome (aged 45.20 ± 15.94 yrs),
– 19 healthy, lean women as a control group (aged 35.55 ± 12.27 yrs).
All participants in the study were recruited from outpatient’s clinic. Informed consent was obtained from all the subjects. The study protocol was accepted by the Bioethical Committee of Medical Centre for Postgraduate Education in Warsaw.
Exclusion criteria were as follows: endocrine disorders, chronic pulmonary dysfunction, chronic kidney and liver disease and neoplasm history. None of the examined subjects had signs of acute infection at the time of the investigation. History of excessive alcohol consumption and/or smoking also eliminated individuals from the study.
Diagnosis of metabolic syndrome
Metabolic syndrome was diagnosed according to the criteria of International Diabetes Federation (IDF 2005). None of the controls had a history of type 2 diabetes and hypolipemic treatment.
Anthropometric measurements
All subjects on the day of examination underwent anthropometric measurements which included height, weight, and waist and hip circumferences estimation. Then, body mass index (BMI) and waist/hip ratios (WHR) were calculated.
Clinical data from all groups were presented in table 1.
Table 1. Anthropometric parameters and blood pressure measurements in all investigated groups.
Control group BMI ≥ 40 MS (-) BMI ≥ 40 MS(+) p
Body Mass Index [BMI]
(kg/m2)
22.09 ± 2.49 42.38 ± 3.32 45.26 ± 3.77 p < 0.05a
p < 0.001b,c
Systolic blood pressure
(mm Hg)
130 ± 27.62 126 ± 19.22 146.7 ± 17.04 p < 0.05a
p < 0.001c
Diastolic blood pressure (mm Hg)71.66 ± 10.40 76.87 ± 14.37 87.64 ± 11.33 p < 0.01b,c
Waist
(cm)
77.16 ± 7.48 112.90 ± 8.39 120.5 ± 6.91 p < 0.05a
p < 0.001b,c
Hip
(cm)
94.72 ± 7.46 132.00 ± 9.37 135.44 ± 8.48 p < 0.001b,c
Waist/hip ratio
[WHR]
0.77 ± 0.05 0.85 ± 0.06 0.89 ± 0.06 p < 0.001b,c
MS (+) – presence of metabolic syndrome
MS (-) – absence of metabolic syndrome
aextreme obesity with metabolic syndrome vs. extreme obesity without metabolic syndrome
bextreme obesity without metabolic syndrome vs. control group
cextreme obesity with metabolic syndrome vs. control group
Analytical methods
Blood samples were taken from all subjects in the morning hours after overnight fasting. Immediately after collections the samples were centrifugated at temperature of 4oC and the obtained plasma was frozen at -70oC.
Fasting plasma glucose levels as well as lipid profile were determined using routine laboratory procedures. Plasma insulin and vaspin levels were estimated using a commercial IRMA kit (from BioSource) and ELISA kit (from AdipoGen), respectively.
Intra and inter assay coefficient was under 10% for all investigated parameters.
Insulin resistance was calculated using a homeostasis model assessment of insulin resistance (HOMA-IR) according to the formula: fasting plasma glucose (mmol/l) x fasting plasma insulin concentration (μIU/ml)/22.5.
Statistical analysis
Statistical analyses were performed using Statistica ver 7.1 PL software. The statistical significance was accepted at p < 0.05.
Evaluation of differences between groups was performed using the Kruskall-Wallis test followed by the Mann-Whitney U test. To calculate correlation coefficient between vaspin and data from anthropometric examination and biochemical parameters, the Spearman test was applied. All results are presented as mean ± SD.
Results
Both groups with extreme obesity presented statistically higher diastolic blood pressure (DBP) than women from the control group. However, DBP did not markedly differ when two subgroups of obese individuals were compared. Whereas systolic blood pressure (SBP) was the highest in morbidly obese individuals with metabolic syndrome, we did not notice any significant differences in SBP between obese subjects without metabolic syndrome and the controls.
Obese women diagnosed with metabolic syndrome had significantly higher waist circumferences than obese individuals with the absence of metabolic syndrome.
When analyzing biochemical parameters, we found the most disturbed lipid profile in the group of obese subjects with metabolic syndrome. Furthermore, as expected, this group showed also heightened disturbances in carbohydrate metabolism with the highest HOMA-IR.
Finally, we also noticed that plasma vaspin concentration was significantly higher in extremely obese women (both with and without metabolic syndrome) in comparison with the controls. However, we did not observe any noticeable differences in vaspin levels among two subgroups of morbidly obese subjects. We identified that vaspin concentration significantly correlated with waist circumference in extremely obese women (R = 0.41; p < 0.05).
All results in detail were presented in table 1 and table 2.
Table 2. Lipid profile, glucose homeostasis parameters and vaspin concentrations in all investigated groups.
Control group BMI ≥ 40 MS (-) BMI ≥ 40 MS (+) p
Total cholesterol
(mg/dl)
205 ± 32.39 198 ± 42.9 208 ± 30.01 ns
Triglycerides
(mg/dl)
88.2 ± 32.9 84.75 ± 28.2 213.38 ± 74.7 p < 0.001a,c
HDL cholesterol
(mg/dl)
63.5 ± 9.87 59.12 ± 13.15 45.22 ± 10.19 p < 0.01a,c
LDL cholesterol
(mg/dl)
119.5 ± 30.67 106 ± 37.10 120.47 ± 24.2 ns
Insulin
(μIU/ml)
9.01 ± 4.64 15.35 ± 12.92 23.55 ± 15.23 p < 0.001b,c
Glucose
(mg/dl)
87.66 ± 11.2 91.08 ± 15.8 123.48 ± 44.1 p < 0.01a
p < 0.001c
HOMA-IR2.3 ± 2.22 3.33 ± 2.37 7.17 ± 5.01 p < 0.01a
p < 0.001b,c
Vaspin
(ng/ml)
0.32 ± 0.28 0.51 ± 0.38 0.65 ± 0.58 p < 0.01b,c
MS (+) – presence of metabolic syndrome
MS (-) – absence of metabolic syndrome
aextreme obesity with metabolic syndrome vs. extreme obesity without metabolic syndrome
bextreme obesity without metabolic syndrome vs. control group
cextreme obesity with metabolic syndrome vs. control group
ns – not significant
Discussion
The role of vaspin in the pathogenesis of obesity and diabetes has not been elucidated completely until today. Although data from animal studies seem promising, the results of research on humans are still inconsistent.
The Otsuka Long-Evans Tokushima Fatty (OLETF) rats serve as an animal model of type 2 diabetes associated with obesity and metabolic disturbances. Interestingly, vaspin was detected for the first time in visceral white adipose tissue of OLETF rats (8). As a result of the animal studies conducted by Hida et al. it has been speculated that vaspin possesses a modulating role in glucose and insulin homeostasis. In details, it has been found that expression of vaspin gene increases with the onset of obesity and insulin resistance in 30 wks old OLETF rats. But in the older subjects (aged 50 wks) in a course of worsening of diabetes, it falls down. However, treatment with insulin or thiazolidinedione or exercise training results in enhanced vaspin mRNA expression (8). The group of Hida and co-workers (8) also demonstrated that glucose homeostasis, presented in the form of insulin sensitivity and glucose tolerance, in mice with diet-induced obesity is ameliorated after administration of recombinant vaspin. Finally, it has been detected that vaspin may affect as well expression of genes of leptin, adiponectin, resistin, GLUT-4 (glucose transporter 4) and TNF alpha. All those compounds mentioned above are believed to be involved in the modulating of glucose metabolism and/or low grade inflammatory process (8).
Studies involving humans concerning changes of vaspin levels in different metabolic conditions remain unclear.
Our research on morbidly obese Polish women revealed that peripheral levels of vaspin were higher in obese patients when compared with normal weight controls. However, no significant differences were observed in comparison of two subgroups with obesity divided according to the presence of metabolic syndrome. Interestingly, data from Spanish study do not confirm in part our findings as serum vaspin concentrations in extremely obese women were not markedly different from those found in controls (9). Moreover, those authors investigated the relationship between vaspin peripheral levels and the presence of metabolic syndrome but no correlations were present. In particular, the absence of correlation between vaspin concentration and BMI, markers of glucose and lipid metabolism was noticed. In addition, mRNA expression in both subcutaneous and visceral adipose tissue of obese subjects was higher than in subjects with BMI within normal range (9). In another study Choi and colleagues analyzed plasma vaspin levels in men and women with metabolic syndrome. Sex associated differences were found. In details, men suffering from metabolic syndrome were characterized with markedly enhanced vaspin levels when compared to metabolically healthy male subjects. Similarly to our data, no differences were found among women with and without metabolic disturbances. Moreover, there was a positive correlation between vaspin and BMI, waist circumference and body fat percentage in men but not in women. Besides, another important finding of this study is that plasma vaspin concentration in women was associated with the presence and severity of atherosclerosis (10).
Results of research conducted by Kim and colleagues are in agreement with the outcome of our study that there is a weak, if any, correlation between vaspin and metabolic syndrome (11). The authors evaluated the effects of 10-months lasting lifestyle modification on compounds of metabolic syndrome and circulating concentrations of adiponectin and vaspin. Although as a result of lifestyle intervention of metabolic syndrome diagnosed patients the significant changes in blood pressure (both diastolic and systolic BP), lipid profile (total cholesterol, triglycerides) and glucose metabolism parameters (insulin concentration and HOMA-IR) were detected, circulating vaspin levels remained unchanged (11).
On the other hand, serum vaspin levels are found to be higher in overweight women with polycystic ovary syndrome (PCOS) (12). It is an important finding as PCOS is associated not only with hormonal abnormalities but also with the higher prevalence of metabolic disturbances including impaired glucose tolerance, type 2 diabetes, dyslipidemia and visceral obesity. Interestingly, Tan et al. also observed that there were markedly higher levels of vaspin mRNA and protein in omental adipose tissue of overweight PCOS women. Moreover, 6 months of metformin therapy resulted in significant decrease of serum vaspin levels with improvement of insulin sensitivity and a decrease in HOMA-IR in those subjects (12). However, other authors reported that although serum vaspin levels are elevated in normal weight subjects with PCOS, neither a small weight loss nor metformin treatment affect vaspin levels (13).
Finally, it should be highlighted that controversies exist about the effect of vaspin on the glucose metabolism in humans. Youn et al. established correlation between enhanced vaspin levels and obesity and impaired glucose sensitivity but not in subjects with type 2 diabetes (14). However, other studies did not confirm association between peripheral levels of vaspin and HOMA-IR in nondiabetic humans (9, 15). Nevertheless, Klöting et al. found that subcutaneous expression of vaspin gene is significantly correlated with waist-to-hip ratio (WHR), fasting plasma insulin concentration and glucose infusion rate during steady state of the euglycemic–hyperinsulinemic clamp (16). Also Tan and colleagues found a positive correlation between serum and omental adipose tissue vaspin levels with glucose and HOMA-IR (12).
To sum up, the results of our study and data provided by other authors indicate that fluctuation of circulating vaspin depends on several factors not only on BMI, glucose metabolism indicators or the presence of metabolic syndrome. In the group of morbidly obese individuals vaspin is not a marker of metabolic disturbances.
**The study was supported with CMKP grant no.501-1-31-22-11.
Piśmiennictwo
1. Erkelens DW, de Bruin TW, Castro Cabezas M: Tulp Syndrome. Lancet 1993; 342: 1536-7.
2. Reaven GM: Banting Lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.
3. Węgierko J: Znaczenie praktyczne podziału cukrzycy na poszczególne jej postacie. Pol Arch Med Wew 1955; 25: 791-7.
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5. Reaven GM: The metabolic syndrome: time to get off the merry-go-round? J Int Med 2010; 269: 127-36.
6. Bergman RN, Kim SP, Hsu IR et al.: Abdominal Obesity: Role in the Pathophysiology of Metabolic Disease and Cardiovascular Risk. Am J Med 2007; 120: S3-S8.
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8. Hida K, Wada J, Eguchi J et al.: Visceral adipose tissue-derived serine protease inhibitor: A unique insulin-sensitizing adipocytokine in obesity. Proc Natl Ac Sci, USA 2005; 102: 10610-5.
9. Auguet T, Quintero Y, Riesco D et al.: New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women. BMC Med Genet 2011; 12: 60.
10. Choi SH, Kwak SH, Lee Y et al.: Plasma vaspin concentrations are elevated in metabolic syndrome in men and are correlated with coronary atherosclerosis in women. Clin Endocrinol (Oxf) 2011; 75: 628-35.
11. Kim SM, Cho GJ, Yannakoulia M et al.: Lifestyle modification increases circulating adiponectin concentration but does not change vaspin concentrations. Metabolism 2011; 60: 1294-9.
12. Tan BK, Heutling D, Chen J et al.: Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 2008; 57: 1501-7.
13. Koiou E, Tziomalos K, Dinas K et al.: The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome. Endocr J 2011; 58: 237-46.
14. Youn BS, Klöting N, Kratzsch J et al.: Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008; 57: 372-7.
15. Von Loeffelholz C, Mohling M, Arafat AM et al.: Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans. Eur J Endocrinol 2010; 162: 507-13.
16. Klöting N, Berndt J, Kralisch S et al.: Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun 2006; 339: 430-6.
otrzymano: 2011-11-30
zaakceptowano do druku: 2011-12-14

Adres do korespondencji:
*Wojciech Bik
Zakład Neuroendokrynologii Klinicznej CMKP
ul. Marymoncka 99/103, 01-813 Warszawa
tel.: (22) 569-38-50, fax: (22) 569-38-59
e-mail: zncmkp@op.pl, zne@cmkp.edu.pl

Postępy Nauk Medycznych 1/2012
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