|
| |
| ORIGINAL ARTICLE |
|
| Ahead of print publication |
|
|
Relationship of serum adiponectin levels with lipid profile in diabetic and non-diabetic pregnant women
Yasmin Akhtar1, Mudassir A Khan1, Muhammad S Khan1, Muhammad K Malik2, Gulalai Rehman3, Seemin Kashif4
1 Department of Biochemistry, Khyber Medical College, Peshawar, Pakistan
2 Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia
3 Balochistan Institute of Nephro-Urology, Quetta, Pakistan
4 Allama Iqbal Open University, Islamabad, Pakistan
| Date of Submission | 01-Aug-2022 |
| Date of Decision | 01-Oct-2022 |
| Date of Acceptance | 13-Jan-2023 |
| Date of Web Publication | 10-Apr-2023 |
Correspondence Address:
Seemin Kashif,
Allama Iqbal Open University, Islamabad
Pakistan
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/njbcs.njbcs_40_22
Context: Adiponectin levels correlate positively with high-density lipoprotein (HDL), and negatively with serum triglyceride (TAG), low-density lipoprotein (LDL), and serum total cholesterol (TC). Aims: To find the relationship of serum adiponectin levels with lipid profiles in diabetic and non-diabetic pregnant women. Settings and Design: The study was performed in four public hospitals and one private tertiary care hospital in Peshawar, Pakistan. This study was a cross-sectional study. Methods and Material: Group A included 100 non-diabetic pregnant women, and Group B included 100 women with gestational diabetes mellitus. Inclusion criteria were a single fetus, 24 to 40 weeks pregnancy, with or without gestational diabetes. Exclusion criteria were multiple pregnancies, pre-existing diabetes, and other comorbidities. The serum adiponectin level and lipid profile of both groups were measured. Statistical Analysis Used: Descriptive analysis of all the variables was done. Independent-sample T-tests, Pearson's correlations, and binary logistic regression analyses were performed on SPSS version 20. Results: Adiponectin level was significantly lower in Group B (2.17 ± 1.84 μg/mL) as compared to Group A (9.94 ± 4.81 μg/mL). HDL level was significantly lower than normal in Group B. TC and LDL levels were higher than normal in both groups. A statistically significant relationship was found between adiponectin and HDL only. Binary logistic regression analysis showed that low adiponectin levels could predict diabetes in pregnancy. Conclusions: Regression analysis could not establish any relationship between adiponectin and lipid profile. However, adiponectin levels could show a relationship with the diabetic group. Hence adiponectin levels could possibly prove to be a biomarker of GDM.
Keywords: Adiponectin, gestational diabetes, lipid profile, pregnancy
How to cite this URL:
Akhtar Y, Khan MA, Khan MS, Malik MK, Rehman G, Kashif S. Relationship of serum adiponectin levels with lipid profile in diabetic and non-diabetic pregnant women. Niger J Basic Clin Sci [Epub ahead of print] [cited 2023 Jun 10]. Available from: https://www.njbcs.net/preprintarticle.asp?id=373995 |
| Introduction | |  |
Adiponectin is a hormone produced by adipose tissue.[1] Its concentration decreases with an increasing amount of adipose tissue. Pregnancy-related weight gain is a normal body response to help the fetus grow. Adiponectin concentrations keep decreasing till the end of pregnancy. Adiponectin levels correlate positively with high-density lipoprotein (HDL),[2] and negatively with serum triglyceride (TAG), low-density lipoprotein (LDL), and total cholesterol (TC) levels.[1],[3]
There is a paucity of studies that explored the relationship of serum adiponectin levels with lipid profile in diabetic and non-diabetic pregnant Pakistani women. This study was aimed at exploring the interplay of these biochemical markers in this population.
| Study Participants and Methods | | |
The study was carried out in four public and one private tertiary care hospital in Peshawar, Khyber Pakhtunkhwa Province, Pakistan. This study was a cross-sectional analytical study. Healthy pregnant women, attending the outpatient departments of these hospitals for a routine antenatal visit, were randomly selected. Inclusion criteria were a single fetus, 24 to 40 weeks pregnancy, with or without type 2 DM with no history of pre-existing or pre-pregnancy diabetes mellitus. There were two groups; Group A included 100 control healthy pregnant women, and Group B included 100 pregnant women with gestational diabetes mellitus. All participants who were included in the study at the outset remained included in the study till the end. Informed consent was taken from patients. The study was approved by the Ethical Committee, on 30th December 2014, with reference number 139/PG/KMC.
Serum adiponectin level was measured on Metrolab ELISA, using Human Adiponectin ELISA kit by Biovendor, Germany. There is a wide variation in adiponectin levels in humans ranging from 1-20 μg/mL, but a cut-off value of 5 μg/mL was selected because it was found to be a level where ≥3 risk factors for cardiovascular risk factors were present.[4] Lipid profiles included serum total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and serum triglyceride (TAG) levels. Cut-off points for lipid profiles were set according to ADA 2018 dyslipidemia guidelines.[5]
| Results | | |
There were a total of 200 pregnant patients, out of which 100 patients were non-diabetic (Group A) and the remaining 100 patients were diabetic (Group B). The mean age of Group A was 21.9 ± 2.67 years, and of Group B was 21.35 ± 2.89. Adiponectin level was significantly higher in Group A i.e., 9.94 ± 4.81 μg/mL, than in Group B i.e., 2.17 ± 1.84 μg/mL [Table 1]. Another statistically significant difference was found in HDL levels (p < 0.05), where HDL was lower than normal in Group B [Table 1]. TC, LDL, VLDL, and TAG were higher than normal in both groups, but except TC, all others were insignificantly higher in Group B [Table 1]. | Table 1: Distribution of mean values of all variables and difference between Group A and Group B
Click here to view |
Out of 200 patients, 59 (29.5%) were in their second trimester of pregnancy, and the remaining 141 (70.5%) were in the third trimester of pregnancy. Mean adiponectin levels were not significantly different from each other [Table 2]. Out of the lipid profile, TC and LDL levels were higher than normal in both groups. Levels of both these parameters were higher in the third trimester and were significantly different (p < 0.01) between these groups [Table 2]. HDL, VLDL, and TAG levels were also high in both groups, and not different from each other. | Table 2: Distribution of mean values of all variables and difference between gestational age groups
Click here to view |
Pearson correlations of adiponectin with lipid profile showed that there was a statistically significant relationship between adiponectin and HDL only [Table 3]. Adiponectin was positively and strongly correlated with HDL levels (p = 0.000, r = 0.82). These tests were also run between these parameters, separately within Group A and B. Significant relationships were found of adiponectin with HDL in both groups, Group A (p = 0.000, r = 0.69), and Group B (p = 0.000, r = 0.65) only [Table 3]. In the whole study group, Chi-square tests showed a significant positive correlation of adiponectin with HDL (p = 0.000, r = 0.56), and a weak negative correlation with LDL (p = 0.039, r = -0.14) and TAG (p = 0.048, r = -0.14) [Table 3]. However, only Group A showed a significant positive correlation between adiponectin and HDL (p = 0.000, r = 0.62).
Binary logistic regression analysis was done to find the predictive strength of adiponectin levels in relation to gestational diabetes. Model [Table 4] showed that low adiponectin levels could moderately predict diabetes in pregnancy in our study population, after adjusting for the age of the patient, gestational age of the fetus, and lipid profile [Table 4]. The variation in the dependent, variable based on our model, ranged from 49.7% to 66.2%, and the model correctly classified about 85.5% of patients [Table 4].
| Discussion | | |
Our study participants comprised 200 pregnant ladies, both diabetic and non-diabetic. Their age ranged from 15 to 28 years. Half of them were diabetic, and the rest were non-diabetic. The relationship of adiponectin levels was studied with lipid profile, in both diabetic and non-diabetic patients.
Maternal metabolism goes through a lot of adaptations to secure pregnancy. These adaptations include a reduction in insulin sensitivity and an increase in β-cell mass and serum insulin levels. In fact, the expression of adiponectin also decreases during normal pregnancy and is believed to augment insulin resistance. Insulin resistance, hence developed, stimulates lipolysis in adipose tissue. This lipolysis is required to meet the energy requirements of the mother's body by production of ketone bodies through lipolysis, because glucose has to be diverted towards the fetus to fulfill the fetus's requirements.[2],[6] Although this insulin resistance is a physiological change, it is one of the main factors leading to gestational diabetes mellitus (GDM). During normal pregnancy, women gain a significant amount of body fat to meet fetal energy requirements, increased energy requirements of the mother herself, and lactation post-partum.[2] But many women gain excessive weight during pregnancy. Obesity, too, reduces insulin sensitivity, making it a risk factor for GDM. Obesity is also accompanied by a decline in adiponectin levels.[7],[8] GDM itself has also been related to an earlier decline in adiponectin levels.[9] Its concentrations are found to be significantly lower in women with GDM compared to non-diabetic pregnant women.[10] Hence, we know that serum adiponectin levels are low in normal pregnancy, and even lower in gestational diabetes. Our study found significantly low levels of adiponectin in diabetic pregnant ladies. Adiponectin was found to be a strong predictor of GDM, irrespective of gestational age as well as of the mother's age, although the maximum age in our study was around 30 years only. Although adiponectin levels were expected to be lower in the third trimester of pregnancy as compared to the second trimester,[10] This decline was not found to be related to gestational age in our study. Adiponectin levels were similar in both trimesters, in both diabetic and non-diabetic groups.
In normal pregnancy, hyperlipidemia develops during the third trimester of pregnancy.[11] There is an increase in insulin resistance and lipolysis as pregnancy advances. This coincides with increased TC and TAG levels. An increase in VLDL levels also occurs along with an increase in both LDL and HDL levels.[11] In our study, about 30% of patients were in their second trimester of pregnancy, and the remaining 70% were in the third trimester. Lipid profile levels were higher than normal in both groups. However, levels of TC, and LDL were significantly higher in the third trimester compared to the second trimester. The levels of TC and LDL were high in diabetic and non-diabetic groups as well, though the differences in their levels were not statistically significant [Table 1]. HDL, VLDL, and TAG levels, on the other hand, were also higher than normal in both trimesters, but their levels were not different in both groups significantly. Our study actually showed a rise in lipid profile in both trimesters, as was expected from metabolic changes in a normal pregnancy. But our results could not show a significant difference between the diabetic and non-diabetic groups in this regard [Table 1].
Adiponectin can prevent the accumulation of lipids in the liver by decreasing fatty acid synthesis and stimulating fatty acid oxidation. Adiponectin probably exerts this effect in the liver through its receptors, AdipoR1 (adiponectin receptor1), and AdipoR2 (adiponectin receptor2).[12] High levels of adiponectin are also related to beneficial outcomes for cardiovascular status.[7],[13],[14] Adiponectin levels are related to lipid profile. Adiponectin levels are positively related to HDL, and negatively related to TG levels.[12],[15],[16] Mean adiponectin levels of our study group (n = 200) were found to be strongly and positively correlated with HDL levels [Table 3]. Adiponectin levels were also weakly and negatively correlated with LDL and TAG levels. However, when this relationship was analyzed individually in Group A and Group B [Table 3], only HDL levels were found to be positively and moderately correlated with adiponectin levels, in both groups.
Hence, in accordance with our previous knowledge, it was found that adiponectin level was very low in those with gestational diabetes. However, the lipid profile was higher than normal in both diabetic and non-diabetic patients, and only HDL was normal in the non-diabetic group [Table 1]. In the diabetic group, the relationship of adiponectin was present with HDL levels alone [Table 3]. It could show its relationship with LDL and TAG in the whole group, but not in the diabetic group alone. Hence, derangement of lipid profile was probably the effect of pregnancy itself, and may likely be independent of diabetes or adiponectin levels. The decline in adiponectin level was probably an effect of increased adiposity and GDM.[9],[10] Hence, adiponectin may likely be a strong predictor of gestational diabetes. As obesity with pregnancy is difficult to differentiate from normal gestational weight gain and edema of pregnancy, measurement of circulating adiponectin might improve the detection of women at high risk of developing GDM,[10] hence managing the latter in time. As adiponectin was known to have several beneficial effects on many organs of the body,[13] efforts should be made to increase its levels. All strategies causing fat loss may likely result in an increase in adiponectin levels.[7] Nutritional interventions like a low-calorie diet, Mediterranean diet, consumption of certain herbal extracts, and even exercise and bariatric surgery might increase adiponectin levels.[7],[17]
The study concluded with the impression that although both serum adiponectin and HDL levels were significantly low in the diabetic group, and their levels were positively correlated, regression analysis could not establish any relationship between adiponectin and HDL levels. However, it did show that adiponectin levels could prove to be a potential biomarker of GDM. Recently, the identification of biomarkers for GDM has attracted much interest. One of these biomarkers could be adiponectin, as studies showed that adiponectin concentrations were significantly low GDM compared to normal pregnant women and that low adiponectin levels in the first trimester were found to be associated with the risk of developing GDM during the second trimester.[6] This interpretation could not be generalized due to the small size of our study, but a larger sample size could be used in the future to generalize these results. The limitation of this study was fewer study participants due to challenges with financial resources.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Monda V, Polito R, Lovino A, Finaldi A, Valenzano A, Nigro E, et al. Short-term physiological effects of a very low-calorie ketogenic diet: Effects on adiponectin levels and inflammatory states. IJMS 2020;21:3228. doi: 10.3390/ijms21093228.  |
| 2. | Yanai H, Yoshida H. Beneficial effects of adiponectin on glucose and lipid metabolism and atherosclerotic progression: Mechanisms and perspectives. IJMS 2019;20:1190. doi: 10.3390/ijms20051190. |
| 3. | Khoramipour K, Chamari K, Hekmatikar AA, Ziyaiyan A, Taherkhani S, Elguindy NM, et al. Adiponectin: Structure, physiological functions, role in diseases, and effects of nutrition. Nutrients 2021;13:1180. doi: 10.3390/nu13041180. |
| 4. | Zhao S, Kusminski CM, Scherer PE. Adiponectin, leptin and cardiovascular disorders. Circ Res 2021;128:136-49. |
| 5. | Rogozińska, Zamora J, Marlin N, Betran AP, Astrup A, Bogaerts A, et al. Gestational weight gain outside the Institute of Medicine recommendations and adverse pregnancy outcomes: Analysis using individual participant data from randomised trials. BMC Pregnancy Childbirth 2019;19:322. doi: 10.1186/s12884-019-2472-7. |
| 6. | Pheiffer C, Dias S, Jack B, Malaza N, Adam S. Adiponectin as a potential biomarker for pregnancy disorders. IJMS 2021;22:1326. doi: 10.3390/ijms22031326. |
| 7. | Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao C, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002;10:1104-10. |
| 8. | De Luis Roman DA, Primo D, IZaola O, Gómez E, López JJ. Adiponectin gene variant rs3774261, effects on lipid profile and adiponectin levels after a high polyunsaturated fat hypocaloric diet with mediterranean pattern. Nutrients 2021;13:1811. doi: 10.3390/nu13061811. |
| 9. | Das AK, Saboo B, Unnikrishnan AG. Current practices and gaps in management of dyslipidemia in type 2 diabetes mellitus (T2DM) in accordance with American Diabetes Association (ADA) Guidelines: A subset analysis from a real-world, cross-sectional observational study (LEADD study). Diabetes Metab Syndr Obes 2021;14:2693-700. |
| 10. | Subhan FB, Shulman L, Yuan Y, McCargar LJ, Kong L, Bell RC. Association of pre-pregnancy BMI and gestational weight gain with fat mass distribution and accretion during pregnancy and early postpartum: A prospective study of Albertan women. BMJ Open 2019;9:e026908. doi: 10.1136/bmjopen-2018-026908. |
| 11. | Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: A promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte 2018;7:57-62. |
| 12. | Gariballa S, Alkaabi J, Yasin J, Al Essa A. Total adiponectin in overweight and obese subjects and its response to visceral fat loss. BMC Endocr Disord 2019;19:55. doi: 10.1186/s12902-019-0386-z. |
| 13. | Bozkurt L, Göbl CS, Baumgartner-Parzer S, Luger A, Pacini G, Kautzky-Willer A. Adiponectin and leptin at early pregnancy: Association to actual glucose disposal and risk for GDM—A prospective cohort study. Int J Endocrinol 2018;2018:1-8. doi: 10.1155/2018/5463762. |
| 14. | Herrera E, Ortega-Senovilla H. Metabolism in normal pregnancy. In: Hod M, Jovanovic LG, Di Renzo GC, de Leiva A, Langer O, editors. Textbook of Diabetes and Pregnancy. 3 rd ed. CRC Press; Boca Raton. 2018. p. 17-27. doi: 10.1201/9781315382104-3. |
| 15. | Hayashi R, Tamada D, Murata M, Kitamura T, Mukai K, Maeda N, et al. Glucocorticoid replacement affects serum adiponectin levels and HDL-C in patients with secondary adrenal insufficiency. J Clin Endocr Metab 2019;104:5814-22. |
| 16. | Shabalala SC, Dludla PV, Mabasa L, Mabasa L, Kappo AP, Basson AK, et al. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed Pharmacother 2020;131:110785. doi: 10.1016/j.biopha. 2020.110785. |
| 17. | Becic T, Studenik C, Hoffmann G. Exercise increases adiponectin and reduces leptin levels in prediabetic and diabetic individuals: Systematic review and meta-analysis of randomized controlled trials. Med Sci 2018;6:97. doi: 10.3390/medsci6040097. |
[Table 1], [Table 2], [Table 3], [Table 4]
|
