Article 163
Association between Omentin Levels and Insulin Resistance in Pregnancy
Affiliations
Key words ▶ omentin ● ▶ insulin resistance ● ▶ pregnancy ●
G. Aktas1, A. Alcelik1, T. Ozlu2, M. Tosun3, B. K. Tekce3, H. Savli1, H. Tekce1, O. Dikbas1 1
Department of Internal Medicine, Abant Izzet Baysal University Hospital, Bolu, Turkey Department of Obstetrics and Gynecology, Abant Izzet Baysal University Hospital, Bolu, Turkey 3 Department of Biochemistry, Abant Izzet Baysal University Hospital, Bolu, Turkey 2
Abstract
▼
Aims: Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, nondiabetic women. Methods: Uncomplicated pregnant women who admit to our outpatient clinics for routine
Introduction received 05.11.2013 first decision 29.01.2014 accepted 05.02.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1370917 Exp Clin Endocrinol Diabetes 2014; 122: 163–166 © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York ISSN 0947-7349 Correspondence G. Aktas, MD Department of Internal Medicine Abant Izzet Baysal University Hospital 14280, Bolu Turkey Tel.: + 90/374/2534 656 Fax: + 90/374/2534 615 [email protected]
▼
Omentin is a new adipokine secreted mainly from visceral adipose tissue. Besides the visceral adipose tissue, it is also expressed in heart, placenta and ovary [1, 2]. Glucose uptake stimulated by insulin in adipocytes is augmented by omentin [2]. It is closely associated with glucose metabolism by triggering Akt signaling, which is an intracellular second messenger of glucose metabolism [3]. Serum omentin is found to be reduced in patients with impaired glucose tolerance and type 2 diabetes mellitus [4, 5]. Insulin resistance and obesity are also associated with a decrease in serum levels of omentin [6]. Diseases characterized with insulin resistance are associated with inflammation [3]. Likewise, omentin is also related with inflammatory conditions [1, 7, 8]. Therefore, it is not surprising that omentin has close association with insulin resistant states, such as prediabetic conditions (impaired fasting glucose and impaired glucose tolerance), pregnancy and obesity.
follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. Results: There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. Conclusion: Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus.
Pregnancy has diabetogenic effects which cause an increase in insulin secretion [9, 10]. Greater insulin levels are needed to maintain normoglycemia during the course of pregnancy [9, 10]. Moreover, the response to intravenous insulin injection is decreased in pregnant women [11]. Therefore, pregnancy is considered as an insulin resistant condition, which is characterized by hyperinsulinemia [12]. To the best of our knowledge, there are few data about omentin levels in pregnancy and its association with insulin resistance. In this study, we aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of nonpregnant, non-diabetic women.
Material and Methods
▼
Uncomplicated pregnant women between 24th– 28th gestational weeks who admit to the outpatient clinics of our institution for routine follow-up were included in the study group. Non-
Aktas G et al. Omentin in Pregnancy … Exp Clin Endocrinol Diabetes 2014; 122: 163–166
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Authors
164 Article
Study group (n = 36)
Control Group (n = 37)
p
Mean ± Standard Deviation age (years) diastolic blood pressure (mmHg)
28.6 ± 7.2 74.7 ± 9.4
48 ± 8.6 76.9 ± 8.6
< 0.001 0.31
Table 1 Comparison of general characteristics and laboratory data of the subjects in study and control groups.
Median (Min–Max) 110.5 (100–148) 81 (72–117) 11.9 (3.7–61.7) 2.5 (0.7–15.5) 198 (80–615) 64 (51.5–88) 25.7 (20.6–38.4)
Glucose < 140 mg/dl (n = 25)
120 (100–150) 100 (73–109) 8.5 (2–17) 1.7 (0.4–4.6) 294 (75–708) 68 (53–83) 27 (19–35)
Glucose ≥ 140 mg/dl (n = 11)
0.08 0.004 0.008 0.07 0.001 0.069 0.272
P
Mean ± Standard Deviation age (years) diastolic blood pressure (mmHg)
27 ± 6.7 74.4 ± 9.9
32 ± 7.3 75.5 ± 8.3
0.07 0.75
110 (100–125) 91 (72–117) 11.6 (4.7–21.6) 2.56 (0.9–4.1) 208 (134–340) 67 (54–81) 26.6 (23.5–32)
0.55 0.14 0.92 0.59 0.63 0.132 0.080
Median (Min–Max) systolic blood pressure (mmHg) fasting plasma glucose (mg/dl) fasting insulin (μIU/ml) HOMA-IR serum omentin (ng/ml) body weight (kg) body mass index (kg/m2)
110 (100–148) 79 (73–108) 12.2 (3.7–61.8) 2.4 (0.7–15.5) 193 (80–165) 61 (51.5–88) 25.2 (20.6–38.4)
pregnant women without diabetes mellitus were included as control group. Exclusion criteria were hypothyroidism, hyperthyroidism, diabetes mellitus and a history of gestational diabetes. Informed consent was obtained from all participants. 50 g oral glucose challenge test was performed to all pregnant women between 24th–28th weeks of gestation. Cases with an elevated result ( ≥ 140 mg/dL) at the 50 g glucose challenge test were included in the study if gestational diabetes was ruled out with a 100 g oral glucose tolerance test (OGTT). A 75 g OGTT was performed for control subjects with fasting plasma glucose ≥ 100 mg/dL and they were included in the study after ruling out diabetes mellitus with this test. Fasting blood samples were obtained and stored at − 80 ℃ until the time of omentin and insulin assessment. Homeostasis model assessment of insulin resistance (HOMA- IR) was calculated with the following formula: fasting plasma glucose (mg/dL) × fasting plasma insulin (μU/mL)/405. Insulin resistance was considered to be present if the HOMA-IR value was > 2.5. Patient characteristics and laboratory data were recorded. SPSS 15.0 for Windows was used for statistical analysis. Normally distributed variables were evaluated with student t test and expressed as mean ± Standard Deviation. Non-homogeneous variables were evaluated with Mann-Whitney U test and expressed as median (min-max). A p-value < 0.05 was considered to be statistically significant. Univariate analysis of variance was performed for detection of the effect of age on omentin levels in the study and control groups. The study was approved by local ethics committee of Abant Izzet Baysal University.
Table 2 Comparison of general characteristics and laboratory data of pregnant women that plasma glucose lower than 140 mg/dl and 140 mg/dl or above in 50 g glucose challange test.
Results
▼
General characteristics and laboratory data of the study and ▶ Table 1. There were 36 pregnant control groups are shown in ● women in the study group and 37 healthy, non-pregnant women in the control group. Mean age of the subjects in the study and control groups were 28.6 ± 7.2 and 48 ± 8.6 years, respectively (p < 0.001). Systolic and diastolic blood pressures of the subjects were not statistically different between study and control groups (p > 0.05). There were no significant differences between study and control groups in terms of body mass index and body weight (p > 0.05 for both). Mean HOMA-IR of study and the control groups were also similar (p > 0.05). However, omentin (p = 0.001) and fasting glucose (p = 0.004) levels were significantly lower in study group than that of the control group. On the other hand, fasting insulin in the study group was significantly increased compared to control group (p = 0.008). Univariate analysis of variance was performed to compare omentin levels between the study and control groups according to age difference. Omentin levels adjusted to age were still significantly different between the study and control groups (p = 0.016). We also compared the general characteristics and laboratory data of pregnant women with a normal and an elevated result ( ≥ 140 mg/dl) at the 50 g glucose challenge test and found that ▶ Table 2). the data were similar in these two groups (● Insulin resistance in study group was significantly more fre▶ Table 3). quent than that of control group (●
Aktas G et al. Omentin in Pregnancy … Exp Clin Endocrinol Diabetes 2014; 122: 163–166
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
systolic blood pressure (mmHg) fasting plasma glucose (mg/dl) fasting insulin (μIU/ml) HOMA-IR serum omentin (ng/ml) body weight (kg) body mass index (kg/m2)
Table 3 Comparison of the frequency of insulin resistance in study and control groups. Groups study group (n = 36) control group (n = 37)
p
Insulin resistance Negative ( %)
Positive ( %)
52.8 75.7
47.2 24.3
0.041*
*Pearson Chi-square test
Discussion
▼
In this study, we found that, serum omentin levels of pregnant women were significantly lower compared to healthy controls. Furthermore, fasting insulin was also significantly increased in pregnant women compared to control subjects. Literature is full of data reporting an association between omentin and insulin resistance. An exception is Orlik et al.’s study, which reported similar omentin levels in women both with and without polycystic ovary syndrome [13]. The majority of studies in the literature pointed of an association between lower omentin levels and insulin resistance. Tan et al. reported lower omentin levels in women with polycystic ovary syndrome, which is another insulin resistant condition [14]. Omentin levels were increased and insulin sensitivity was improved by weight loss in Moreno-Navarrete et al.’s study [15]. It has been shown that omentin levels were elevated after metformin treatment, a drug that improves insulin resistance [16]. In another study, it has been found that omentin levels of diabetic end stage renal disease patients were significantly lower than the non-diabetic end stage renal disease patients [17]. So, serum omentin levels seem to decrease in subjects with impaired glucose regulation [5, 18, 19]. It is known that pregnancy is an insulin resistant condition characterized with hyperinsulinemia [12]. Correlated with the literature, we found that pregnant women, who also have insulin resistance, have lower omentin and higher insulin levels compared to controls. Therefore, we can say that, besides an increase in insulin levels, pregnancy may cause a reduction in omentin levels similar to the other insulin resistant states such as obesity, polycystic ovary syndrome, and type 2 diabetes mellitus. In our study, pregnant women were more likely to have higher HOMA-IR levels compared to the control group, although the difference was not statistically significant. Higher HOMA IR levels, as well as increased fasting plasma insulin are features seen in insulin resistant states. As mentioned before, insulin resistance (subjects with HOMA IR ≥ 2.5) was significantly more common in pregnant women than controls. Fasting glucose levels were significantly lower in pregnant women compared to controls, and this may be one of the reasons why comparison of HOMA IR between the study and control groups remained nonsignificant. Another possible explanation for this condition might be referred to the fact that we ruled out diabetes mellitus but not impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) in the control group. Both IFG and IGT are prediabetic states characterized by hyperinsulinemia. With the 50 g glucose challenge test which is used as a screening test for gestational diabetes mellitus, if the plasma glucose value checked 1 h after the glucose load is < 140 mg/dL, the result is accepted to be normal. However, pregnant women with an elevated result ( ≥ 140 mg/dL) have a higher risk of having gestational diabetes mellitus which can be ruled out by a diagnostic 100 g OGTT. Serum omentin levels of pregnant women with an
elevated ( ≥ 140 mg/dL) 50 g glucose challenge test (the group with a higher risk of gestational diabetes) were lower than that of pregnant women with a normal 50 g glucose test, but the difference was not statistically significant. DeSouza Batista et al. reported that obesity causes a reduction in the serum levels of omentin [6]. Body weight and BMI of the study and control groups were similar in our study. Therefore, the difference in omentin levels between the study and control groups are not related to the body weight or BMI. In a recent study, omentin levels of 20 pregnant women with gestational diabetes mellitus were compared with that of 23 healthy subjects [20]. No statistically significant differences were detected between the groups in terms of serum omentin levels, fasting insulin and HOMA-IR levels [20]. Blood samples were obtained during oral glucose tolerance test in the mentioned study, but it is not clear whether omentin is assessed in fasting blood samples or after oral glucose ingestion. This is important, because an increase in plasma glucose results in a reduction in circulating serum omentin levels [14]. However, we found that serum omentin of pregnant women without GDM was significantly lower and fasting insulin was significantly higher compared to control subjects. We emphasize that we assessed fasting omentin levels of participants, in our study. Reduction in HbA1c levels are reported in pregnant women compared to non-pregnant subjects [21]. Reduced HbA1c levels reflect lower plasma glucose levels. We also found reduced fasting plasma glucose levels in pregnant women compared to control subjects. In our study, pregnant women were significantly younger than women in the control group what makes the interpretation of our results difficult. Although this appears to be a limitation of our results, it is clear that, insulin resistance and type 2 diabetes mellitus is more common in elderly. To overcome this limitation at least partially, we included in the control group those subjects who were free of diabetes mellitus. We were also able to overcome the effect increasing BMI with age on glucose metabolism since the BMI of the subjects were similar between the two groups. Although we would expect elevated fasting insulin and lower serum omentin levels in older people, serum omentin levels were significantly higher and fasting insulin was significantly lower in our control group compared to pregnant women. Because pregnancy is more common in younger women in this region of our country, we could not be able to compare pregnant women with age matched controls. In the light of the findings of this study, we conclude that omentin levels significantly decrease in pregnant women. However, larger prospective studies are needed to claim whether omentin predicts insulin resistance and whether it can have a clinical use for diagnosis of gestational diabetes mellitus.
Funding statement: This work has not been funded by any organization. Conflict of interest: None to declare. References 1 Schaffler A, Neumeier A, Herfarth H et al. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96–102 2 Yang RZ, Lee MJ, Hu H et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006; 290: E1253–E1261
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3 Tan BK, Adya R, Randeva HS. Omentin: A Novel Link Between Inflammation, Diabesity, and Cardiovascular Disease. Trends Cardiovasc Med 2010; 20: 143–148 4 Cai RC, Wei L, Di JZ et al. Expression of omentin in adipose tissues in obese and type 2 diabetic patients. Zhonghua yi xue za zhi 2009; 89: 381–384 5 Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes research and clinical practice 2010; 88: 29–33 6 de Souza Batista CM, Yang RZ, Lee MJ et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655–1661 7 Dandona P, Aljada A, Chaudhuri A et al. Metabolic syndrome – A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005; 111: 1448–1454 8 Senolt L, Polanska M, Filkova M et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 1410–1411 9 Knopp RH, Montes A, Warth MR. Carbohydrate and lipid metabolism. Laboratory Indices of Nutritional Status in Pregnancy. Washington, D.C: National Academy of Sciences, 1978; 35–88 10 Freinkel N, Phelps RL, Metzger BE. Intermediary metabolism during normal pregnancy. In: Sutherland HW, Stowers JM (ed.). Carbohydrate Metabolism in Pregnancy and the Newborn. New York: Springer-Verlag, 1979; 1–31 11 Burt RL, Davidson IW. Insulin half-life and utilization in normal pregnancy. Obstet Gynecol 1974; 43: 161–170 12 Berson SA, Yalow RS. Insulin “antagonists” and insulin resistance. In: Ellenberg M, Rifkin H (ed.). Diabetes Mellitus: Theory and Practice. New York: McGraw-Hill, 1970; 388–423
13 Orlik B, Madej P, Owczarek A et al. Plasma omentin and adiponectin levels as markers of adipose tissue dysfunction in normal weight and obese women with polycystic ovary syndrome. Clin Endocrinol 2013 doi: 10.1111/cen.12381. [Epub ahead of print] 14 Tan BK, Adya R, Farhatullah S et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 2008; 57: 801–808 15 Moreno-Navarrete JM, Catalan V, Ortega F et al. Circulating omentin concentration increases after weight loss. Nutr Metab 2010; 7 16 Tan BK, Adya R, Farhatullah S et al. Metformin Treatment May Increase Omentin-1 Levels in Women With Polycystic Ovary Syndrome. Diabetes 2010; 59: 3023–3031 17 Alcelik A, Tosun M, Ozlu MF et al. Serum Levels of Omentin in EndStage Renal Disease Patients. Kidney Blood Press R 2012; 35: 511–516 18 Tan BK, Pua S, Syed F et al. Decreased plasma omentin-1 levels in Type 1 diabetes mellitus. Diab Med 2008; 25: 1254–1255 19 Yan P, Liu D, Long M et al. Changes of Serum Omentin Levels and Relationship between Omentin and Adiponectin Concentrations in Type 2 Diabetes Mellitus. Exp Clin Endocr Diab 2011; 119: 257–263 20 Lewandowski K, Nadel I, Lewinski A et al. Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices. Ginekol Pol 2010; 81: 907–912 21 Nielsen LR, Ekbom P, Damm P et al. HbA1c levels are significantly lower in early and late pregnancy. Diabetes Care 2004; 27: 1200–1201
Aktas G et al. Omentin in Pregnancy … Exp Clin Endocrinol Diabetes 2014; 122: 163–166
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166 Article
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Association between Omentin Levels and Insulin Resistance in Pregnancy
Affiliations
Key words ▶ omentin ● ▶ insulin resistance ● ▶ pregnancy ●
G. Aktas1, A. Alcelik1, T. Ozlu2, M. Tosun3, B. K. Tekce3, H. Savli1, H. Tekce1, O. Dikbas1 1
Department of Internal Medicine, Abant Izzet Baysal University Hospital, Bolu, Turkey Department of Obstetrics and Gynecology, Abant Izzet Baysal University Hospital, Bolu, Turkey 3 Department of Biochemistry, Abant Izzet Baysal University Hospital, Bolu, Turkey 2
Abstract
▼
Aims: Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, nondiabetic women. Methods: Uncomplicated pregnant women who admit to our outpatient clinics for routine
Introduction received 05.11.2013 first decision 29.01.2014 accepted 05.02.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1370917 Exp Clin Endocrinol Diabetes 2014; 122: 163–166 © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York ISSN 0947-7349 Correspondence G. Aktas, MD Department of Internal Medicine Abant Izzet Baysal University Hospital 14280, Bolu Turkey Tel.: + 90/374/2534 656 Fax: + 90/374/2534 615 [email protected]
▼
Omentin is a new adipokine secreted mainly from visceral adipose tissue. Besides the visceral adipose tissue, it is also expressed in heart, placenta and ovary [1, 2]. Glucose uptake stimulated by insulin in adipocytes is augmented by omentin [2]. It is closely associated with glucose metabolism by triggering Akt signaling, which is an intracellular second messenger of glucose metabolism [3]. Serum omentin is found to be reduced in patients with impaired glucose tolerance and type 2 diabetes mellitus [4, 5]. Insulin resistance and obesity are also associated with a decrease in serum levels of omentin [6]. Diseases characterized with insulin resistance are associated with inflammation [3]. Likewise, omentin is also related with inflammatory conditions [1, 7, 8]. Therefore, it is not surprising that omentin has close association with insulin resistant states, such as prediabetic conditions (impaired fasting glucose and impaired glucose tolerance), pregnancy and obesity.
follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. Results: There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. Conclusion: Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus.
Pregnancy has diabetogenic effects which cause an increase in insulin secretion [9, 10]. Greater insulin levels are needed to maintain normoglycemia during the course of pregnancy [9, 10]. Moreover, the response to intravenous insulin injection is decreased in pregnant women [11]. Therefore, pregnancy is considered as an insulin resistant condition, which is characterized by hyperinsulinemia [12]. To the best of our knowledge, there are few data about omentin levels in pregnancy and its association with insulin resistance. In this study, we aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of nonpregnant, non-diabetic women.
Material and Methods
▼
Uncomplicated pregnant women between 24th– 28th gestational weeks who admit to the outpatient clinics of our institution for routine follow-up were included in the study group. Non-
Aktas G et al. Omentin in Pregnancy … Exp Clin Endocrinol Diabetes 2014; 122: 163–166
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Authors
164 Article
Study group (n = 36)
Control Group (n = 37)
p
Mean ± Standard Deviation age (years) diastolic blood pressure (mmHg)
28.6 ± 7.2 74.7 ± 9.4
48 ± 8.6 76.9 ± 8.6
< 0.001 0.31
Table 1 Comparison of general characteristics and laboratory data of the subjects in study and control groups.
Median (Min–Max) 110.5 (100–148) 81 (72–117) 11.9 (3.7–61.7) 2.5 (0.7–15.5) 198 (80–615) 64 (51.5–88) 25.7 (20.6–38.4)
Glucose < 140 mg/dl (n = 25)
120 (100–150) 100 (73–109) 8.5 (2–17) 1.7 (0.4–4.6) 294 (75–708) 68 (53–83) 27 (19–35)
Glucose ≥ 140 mg/dl (n = 11)
0.08 0.004 0.008 0.07 0.001 0.069 0.272
P
Mean ± Standard Deviation age (years) diastolic blood pressure (mmHg)
27 ± 6.7 74.4 ± 9.9
32 ± 7.3 75.5 ± 8.3
0.07 0.75
110 (100–125) 91 (72–117) 11.6 (4.7–21.6) 2.56 (0.9–4.1) 208 (134–340) 67 (54–81) 26.6 (23.5–32)
0.55 0.14 0.92 0.59 0.63 0.132 0.080
Median (Min–Max) systolic blood pressure (mmHg) fasting plasma glucose (mg/dl) fasting insulin (μIU/ml) HOMA-IR serum omentin (ng/ml) body weight (kg) body mass index (kg/m2)
110 (100–148) 79 (73–108) 12.2 (3.7–61.8) 2.4 (0.7–15.5) 193 (80–165) 61 (51.5–88) 25.2 (20.6–38.4)
pregnant women without diabetes mellitus were included as control group. Exclusion criteria were hypothyroidism, hyperthyroidism, diabetes mellitus and a history of gestational diabetes. Informed consent was obtained from all participants. 50 g oral glucose challenge test was performed to all pregnant women between 24th–28th weeks of gestation. Cases with an elevated result ( ≥ 140 mg/dL) at the 50 g glucose challenge test were included in the study if gestational diabetes was ruled out with a 100 g oral glucose tolerance test (OGTT). A 75 g OGTT was performed for control subjects with fasting plasma glucose ≥ 100 mg/dL and they were included in the study after ruling out diabetes mellitus with this test. Fasting blood samples were obtained and stored at − 80 ℃ until the time of omentin and insulin assessment. Homeostasis model assessment of insulin resistance (HOMA- IR) was calculated with the following formula: fasting plasma glucose (mg/dL) × fasting plasma insulin (μU/mL)/405. Insulin resistance was considered to be present if the HOMA-IR value was > 2.5. Patient characteristics and laboratory data were recorded. SPSS 15.0 for Windows was used for statistical analysis. Normally distributed variables were evaluated with student t test and expressed as mean ± Standard Deviation. Non-homogeneous variables were evaluated with Mann-Whitney U test and expressed as median (min-max). A p-value < 0.05 was considered to be statistically significant. Univariate analysis of variance was performed for detection of the effect of age on omentin levels in the study and control groups. The study was approved by local ethics committee of Abant Izzet Baysal University.
Table 2 Comparison of general characteristics and laboratory data of pregnant women that plasma glucose lower than 140 mg/dl and 140 mg/dl or above in 50 g glucose challange test.
Results
▼
General characteristics and laboratory data of the study and ▶ Table 1. There were 36 pregnant control groups are shown in ● women in the study group and 37 healthy, non-pregnant women in the control group. Mean age of the subjects in the study and control groups were 28.6 ± 7.2 and 48 ± 8.6 years, respectively (p < 0.001). Systolic and diastolic blood pressures of the subjects were not statistically different between study and control groups (p > 0.05). There were no significant differences between study and control groups in terms of body mass index and body weight (p > 0.05 for both). Mean HOMA-IR of study and the control groups were also similar (p > 0.05). However, omentin (p = 0.001) and fasting glucose (p = 0.004) levels were significantly lower in study group than that of the control group. On the other hand, fasting insulin in the study group was significantly increased compared to control group (p = 0.008). Univariate analysis of variance was performed to compare omentin levels between the study and control groups according to age difference. Omentin levels adjusted to age were still significantly different between the study and control groups (p = 0.016). We also compared the general characteristics and laboratory data of pregnant women with a normal and an elevated result ( ≥ 140 mg/dl) at the 50 g glucose challenge test and found that ▶ Table 2). the data were similar in these two groups (● Insulin resistance in study group was significantly more fre▶ Table 3). quent than that of control group (●
Aktas G et al. Omentin in Pregnancy … Exp Clin Endocrinol Diabetes 2014; 122: 163–166
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
systolic blood pressure (mmHg) fasting plasma glucose (mg/dl) fasting insulin (μIU/ml) HOMA-IR serum omentin (ng/ml) body weight (kg) body mass index (kg/m2)
Table 3 Comparison of the frequency of insulin resistance in study and control groups. Groups study group (n = 36) control group (n = 37)
p
Insulin resistance Negative ( %)
Positive ( %)
52.8 75.7
47.2 24.3
0.041*
*Pearson Chi-square test
Discussion
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In this study, we found that, serum omentin levels of pregnant women were significantly lower compared to healthy controls. Furthermore, fasting insulin was also significantly increased in pregnant women compared to control subjects. Literature is full of data reporting an association between omentin and insulin resistance. An exception is Orlik et al.’s study, which reported similar omentin levels in women both with and without polycystic ovary syndrome [13]. The majority of studies in the literature pointed of an association between lower omentin levels and insulin resistance. Tan et al. reported lower omentin levels in women with polycystic ovary syndrome, which is another insulin resistant condition [14]. Omentin levels were increased and insulin sensitivity was improved by weight loss in Moreno-Navarrete et al.’s study [15]. It has been shown that omentin levels were elevated after metformin treatment, a drug that improves insulin resistance [16]. In another study, it has been found that omentin levels of diabetic end stage renal disease patients were significantly lower than the non-diabetic end stage renal disease patients [17]. So, serum omentin levels seem to decrease in subjects with impaired glucose regulation [5, 18, 19]. It is known that pregnancy is an insulin resistant condition characterized with hyperinsulinemia [12]. Correlated with the literature, we found that pregnant women, who also have insulin resistance, have lower omentin and higher insulin levels compared to controls. Therefore, we can say that, besides an increase in insulin levels, pregnancy may cause a reduction in omentin levels similar to the other insulin resistant states such as obesity, polycystic ovary syndrome, and type 2 diabetes mellitus. In our study, pregnant women were more likely to have higher HOMA-IR levels compared to the control group, although the difference was not statistically significant. Higher HOMA IR levels, as well as increased fasting plasma insulin are features seen in insulin resistant states. As mentioned before, insulin resistance (subjects with HOMA IR ≥ 2.5) was significantly more common in pregnant women than controls. Fasting glucose levels were significantly lower in pregnant women compared to controls, and this may be one of the reasons why comparison of HOMA IR between the study and control groups remained nonsignificant. Another possible explanation for this condition might be referred to the fact that we ruled out diabetes mellitus but not impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) in the control group. Both IFG and IGT are prediabetic states characterized by hyperinsulinemia. With the 50 g glucose challenge test which is used as a screening test for gestational diabetes mellitus, if the plasma glucose value checked 1 h after the glucose load is < 140 mg/dL, the result is accepted to be normal. However, pregnant women with an elevated result ( ≥ 140 mg/dL) have a higher risk of having gestational diabetes mellitus which can be ruled out by a diagnostic 100 g OGTT. Serum omentin levels of pregnant women with an
elevated ( ≥ 140 mg/dL) 50 g glucose challenge test (the group with a higher risk of gestational diabetes) were lower than that of pregnant women with a normal 50 g glucose test, but the difference was not statistically significant. DeSouza Batista et al. reported that obesity causes a reduction in the serum levels of omentin [6]. Body weight and BMI of the study and control groups were similar in our study. Therefore, the difference in omentin levels between the study and control groups are not related to the body weight or BMI. In a recent study, omentin levels of 20 pregnant women with gestational diabetes mellitus were compared with that of 23 healthy subjects [20]. No statistically significant differences were detected between the groups in terms of serum omentin levels, fasting insulin and HOMA-IR levels [20]. Blood samples were obtained during oral glucose tolerance test in the mentioned study, but it is not clear whether omentin is assessed in fasting blood samples or after oral glucose ingestion. This is important, because an increase in plasma glucose results in a reduction in circulating serum omentin levels [14]. However, we found that serum omentin of pregnant women without GDM was significantly lower and fasting insulin was significantly higher compared to control subjects. We emphasize that we assessed fasting omentin levels of participants, in our study. Reduction in HbA1c levels are reported in pregnant women compared to non-pregnant subjects [21]. Reduced HbA1c levels reflect lower plasma glucose levels. We also found reduced fasting plasma glucose levels in pregnant women compared to control subjects. In our study, pregnant women were significantly younger than women in the control group what makes the interpretation of our results difficult. Although this appears to be a limitation of our results, it is clear that, insulin resistance and type 2 diabetes mellitus is more common in elderly. To overcome this limitation at least partially, we included in the control group those subjects who were free of diabetes mellitus. We were also able to overcome the effect increasing BMI with age on glucose metabolism since the BMI of the subjects were similar between the two groups. Although we would expect elevated fasting insulin and lower serum omentin levels in older people, serum omentin levels were significantly higher and fasting insulin was significantly lower in our control group compared to pregnant women. Because pregnancy is more common in younger women in this region of our country, we could not be able to compare pregnant women with age matched controls. In the light of the findings of this study, we conclude that omentin levels significantly decrease in pregnant women. However, larger prospective studies are needed to claim whether omentin predicts insulin resistance and whether it can have a clinical use for diagnosis of gestational diabetes mellitus.
Funding statement: This work has not been funded by any organization. Conflict of interest: None to declare. References 1 Schaffler A, Neumeier A, Herfarth H et al. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96–102 2 Yang RZ, Lee MJ, Hu H et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006; 290: E1253–E1261
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3 Tan BK, Adya R, Randeva HS. Omentin: A Novel Link Between Inflammation, Diabesity, and Cardiovascular Disease. Trends Cardiovasc Med 2010; 20: 143–148 4 Cai RC, Wei L, Di JZ et al. Expression of omentin in adipose tissues in obese and type 2 diabetic patients. Zhonghua yi xue za zhi 2009; 89: 381–384 5 Pan HY, Guo L, Li Q. Changes of serum omentin-1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes research and clinical practice 2010; 88: 29–33 6 de Souza Batista CM, Yang RZ, Lee MJ et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655–1661 7 Dandona P, Aljada A, Chaudhuri A et al. Metabolic syndrome – A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005; 111: 1448–1454 8 Senolt L, Polanska M, Filkova M et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 2010; 69: 1410–1411 9 Knopp RH, Montes A, Warth MR. Carbohydrate and lipid metabolism. Laboratory Indices of Nutritional Status in Pregnancy. Washington, D.C: National Academy of Sciences, 1978; 35–88 10 Freinkel N, Phelps RL, Metzger BE. Intermediary metabolism during normal pregnancy. In: Sutherland HW, Stowers JM (ed.). Carbohydrate Metabolism in Pregnancy and the Newborn. New York: Springer-Verlag, 1979; 1–31 11 Burt RL, Davidson IW. Insulin half-life and utilization in normal pregnancy. Obstet Gynecol 1974; 43: 161–170 12 Berson SA, Yalow RS. Insulin “antagonists” and insulin resistance. In: Ellenberg M, Rifkin H (ed.). Diabetes Mellitus: Theory and Practice. New York: McGraw-Hill, 1970; 388–423
13 Orlik B, Madej P, Owczarek A et al. Plasma omentin and adiponectin levels as markers of adipose tissue dysfunction in normal weight and obese women with polycystic ovary syndrome. Clin Endocrinol 2013 doi: 10.1111/cen.12381. [Epub ahead of print] 14 Tan BK, Adya R, Farhatullah S et al. Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 2008; 57: 801–808 15 Moreno-Navarrete JM, Catalan V, Ortega F et al. Circulating omentin concentration increases after weight loss. Nutr Metab 2010; 7 16 Tan BK, Adya R, Farhatullah S et al. Metformin Treatment May Increase Omentin-1 Levels in Women With Polycystic Ovary Syndrome. Diabetes 2010; 59: 3023–3031 17 Alcelik A, Tosun M, Ozlu MF et al. Serum Levels of Omentin in EndStage Renal Disease Patients. Kidney Blood Press R 2012; 35: 511–516 18 Tan BK, Pua S, Syed F et al. Decreased plasma omentin-1 levels in Type 1 diabetes mellitus. Diab Med 2008; 25: 1254–1255 19 Yan P, Liu D, Long M et al. Changes of Serum Omentin Levels and Relationship between Omentin and Adiponectin Concentrations in Type 2 Diabetes Mellitus. Exp Clin Endocr Diab 2011; 119: 257–263 20 Lewandowski K, Nadel I, Lewinski A et al. Positive correlation between serum omentin and thrombospondin-1 in gestational diabetes despite lack of correlation with insulin resistance indices. Ginekol Pol 2010; 81: 907–912 21 Nielsen LR, Ekbom P, Damm P et al. HbA1c levels are significantly lower in early and late pregnancy. Diabetes Care 2004; 27: 1200–1201
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