|Year : 2020 | Volume
| Issue : 3 | Page : 801-805
Serum adiponectin level in osteoporotic postmenopausal women with type 2 diabetes mellitus
Mohammed A Shaaban1, Mohammed G Habsh2, Rasha G Mostafa3, Shimaa K Zewain1
1 Internal Medicine Department, Faculty of Medicine, Menoufia, Egypt
2 Tusun Hospital, Abu Qir, Alexandria, Egypt
3 Microbiology and Immunology Department, Faculty of Medicine, Menoufia, Egypt
|Date of Submission||13-Mar-2020|
|Date of Decision||22-Apr-2020|
|Date of Acceptance||10-May-2020|
|Date of Web Publication||30-Sep-2020|
Mohammed G Habsh
Internal Medicine Department, Faculty of Medicine, Yassin Abdel Ghafar Street from Gamal Abdel Naser Street, Shebin El Kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim was to evaluate the relationships between serum adiponectin level and lumbar bone mineral density (BMD) in osteoporotic postmenopausal women with or without type 2 diabetes mellitus.
Adiponectin is a novel adipocytokine that could influence bone metabolism.
Patients and methods
This case–control study was conducted on 55 postmenopausal women selected from diabetic endocrinology inpatient and outpatient clinics. Patients were divided into three groups: osteoporotic group (group A), which included 20 nondiabetic osteoporotic postmenopausal women; diabetic osteoporotic group (group B), which included 20 type 2 diabetic osteoporotic postmenopausal women; and control group (group C), which included 15 nonosteoporotic, nondiabetic women postmenopausal. All patients were subjected to complete history, clinical examination, we measured and recorded the anthropometric measures, fasting blood sugar, hemoglobin A1c, serum calcium, serum phosphorus, parathyroid hormone, thyroid-stimulating hormone, erythrocyte sedimentation rate, C-reactive protein, serum adiponectin levels measured by ELISA, and lumbar spine BMD by dual-energy x-ray absorptiometry scan.
In osteoporotic group (group A), serum adiponectin had a negative significant correlation with BMD (r=−0.45 and P = 0.04). The diabetic osteoporotic postmenopausal group (group B) showed the lowest concentration of serum adiponectin (μg/ml) compared with group A and the control. Lumbar BMD of group B was significantly higher than that of group A.
Serum adiponectin is associated with lumber BMD in osteoporotic postmenopausal women, which suggests that serum adiponectin was involved in bone metabolism.
Keywords: adiponectin, bone mineral density, diabetes mellitus, osteoporotic, postmenopausal
|How to cite this article:|
Shaaban MA, Habsh MG, Mostafa RG, Zewain SK. Serum adiponectin level in osteoporotic postmenopausal women with type 2 diabetes mellitus. Menoufia Med J 2020;33:801-5
|How to cite this URL:|
Shaaban MA, Habsh MG, Mostafa RG, Zewain SK. Serum adiponectin level in osteoporotic postmenopausal women with type 2 diabetes mellitus. Menoufia Med J [serial online] 2020 [cited 2021 Apr 18];33:801-5. Available from: http://www.mmj.eg.net/text.asp?2020/33/3/801/296714
| Introduction|| |
Diabetes mellitus is the most common comorbidity worldwide, and its incidence has increased dramatically over the coming decades. Diabetic patients are at risk of various complications, such as impaired bone health. Cumulative data revealed that there is a positive correlation between bone mineral density (BMD) and adipose tissue .
Adiponectin is a novel adipocytokine that is highly expressed in fat depots either in visceral, subcutaneous, and bone marrow. The adiponectin receptor in osteoblasts was responsible for proliferation, differentiation, and mineralization of osteoblastic cells, and this suggests that adiponectin could influence bone metabolism .
The literature reports suggest a link between plasma levels of adiponectin and BMD, which draws attention to the possible use of adiponectin as an indicator of osteoporotic changes. So the relationships of serum adiponectin with BMD need to be clarified further to solve this discrepancy .
In this study, we investigated the relationships between serum adiponectin versus lumbar BMD in osteoporotic postmenopausal women with and without type 2 diabetes.
| Patients and Methods|| |
This case–control study was conducted on 55 postmenopausal women selected from Diabetic Endocrinology inpatient and outpatient clinics during the period from October 2018 to April 2019 after Ethical Committee permission and obtained signed consent from every patient. Patients were divided into three groups: group A included 20 nondiabetic osteoporotic postmenopausal women, group B included 20 type 2 diabetic osteoporotic postmenopausal women, and group C included 15 nonosteoporotic, nondiabetic women postmenopausal as a control group.
Patients having inflammatory disease, history of recent infection, autoimmune disease, liver disease, chronic kidney disease, endocrinal disease, disease or risk factor for osteoporosis, nutritional derangements, or disturbance of physical activity were excluded.
All patients were subjected to complete history, full clinical examination, personal history (age, sex, residence, and occupation), we measured and recorded the anthropometric measures [weight, height, and BMI = weight (kg)/square height (m2)], waist circumference, hip circumference, and waist-to-hip ratio (WHR).
All measurements were performed when the patients were in a standing position with feet together, relaxed abdomen, and arms at their sides. Waist circumference was measured in standing position by placing a soft tape measure midway between the lowest rib and the iliac crest, and hip circumference was measured at the level of the greater trochanter.
WHR was calculated as waist circumference divided by hip circumference. Routine investigations, such as fasting blood sugar (FBG), hemoglobin A1c, serum calcium, serum phosphorus, parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate, C-reactive protein (CRP), serum adiponectin levels by ELISA kits, and lumbar spine BMD (anterior-posterior projection at L1–L4) of all women measured by dual-energy x-ray absorptiometry were done.
The data were analyzed with the Statistical Package for the Social Sciences version 22.0 on IBM compatible computer (SPSS Inc., Chicago, Illinois, USA). Quantitative variables were presented as mean ± SD and range. Independent test was used to estimate the differences in quantitative variables. One-way analysis of variance test was used for comparison among three or more groups having quantitative variables. Pearson correlation (r) was used to measure the association between two quantitative variables. P value of less than 0.05 was considered statistically significant, and less than 0.001 was considered highly statistically significant.
| Results|| |
[Table 1] shows that the mean age and height were comparable among the three groups (P = 0.25 and 0.32, respectively). On the contrary, there were significantly differences among the three groups in weight, BMI, and serum adiponectin (P = 0.01, 0.005, and 0.03, respectively). Moreover, there were significantly differences among the three groups in waist circumference, hip circumference, WHR, FBG, serum calcium, serum phosphorus, serum TSH, serum PTH, serum CRP and BMD (P < 0.001 for all). There was a significant difference between groups A and B in weight (P = 0.008), BMI (P = 0.009), WHR (P = 0.02), BMD (P = 0.02), serum calcium (P < 0.001), serum TSH (P = 0.007), and serum CRP (P = 0.004), and between group A and control in weight (P = 0.007), waist circumference (P = 0.001), hip circumference (P = 0.003), BMI (P = 0.002), WHR (P < 0.001), BMD (P < 0.001), FBG (P < 0.001), glycosylated hemoglobin (HA1C) (P < 0.001), serum phosphorus (P < 0.001), serum PTH (P < 0.001), serum TSH (P < 0.001), serum CRP (P < 0.001), and serum adiponectin (P = 0.009). There was a significant difference between groups A and B and between group A and control in serum calcium (Ca) (P < 0.001 for all). Moreover, comparison between group B and control showed significant difference in waist circumference and hip circumference (P < 0.001), WHR (P < 0.001), BMD (P < 0.001), FBG (P < 0.001), HA1C (P < 0.001), serum calcium (P < 0.001), serum phosphorus (P < 0.001), serum TSH (P < 0.001), serum PTH (P < 0.001), serum CRP (P < 0.001), and serum adiponectin (P = 0.07).
|Table 1: Comparison between groups regarding anthropometric and demographic data and laboratory values (analysis of variance)|
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[Table 2] shows that in group A, serum adiponectin had a negative significant correlation with BMD (r=−0.45 and P = 0.04) and BMI (r=−0.49 and P = 0.03) and nonsignificant correlation with all the remaining parameters. In group B, serum adiponectin had a negative significant correlation with FBG (r=−0.45 and P = 0.049), BMI (r=−0.56 and P = 0.01), and weight (r=−0.61 and P = 0.004) and nonsignificant correlation with BMD (r = 0.36 and P = 0.12) and all other remaining parameters. On the contrary, in control group, there was a positive significant correlation between serum adiponectin and PTH (r = 0.58 and P = 0.03) and nonsignificant correlations with all other remaining parameters.
| Discussion|| |
In our study, the mean age and height were comparable among the three groups. On the contrary, there was a significantly difference among the three groups in weight and BMI (P = 0.01 and 0.005, respectively). As adiponectin is a adipocytokine, its concentration is greatly affected by anthropometric measures, but fortunately, its actual level is affected by the estimation of Fat % score, which has been reported in many studies, and as body weight, one of the strongest predictors of BMD, is inversely associated with postmenopausal bone loss and bone turnover, it explains the difference in weight between cases and control group, as reported by many studies ,,,. A few studies have shown that lipid metabolism may be affected by adiponectin and perhaps insulin resistance ,. A dissimilar observation was reported by Lenchik et al. , as adiponectin was not significantly associated with BMI, height, weight, or waist circumference. There are reports showing an inverse association between adiponectin concentration and BMI in women of different ages ,,,.
In agreement with us, Al-Osami and Hameed  found insignificant differences in the age, but against us, the BMI was insignificantly changed between studied groups. Moreover, many authors suggested that the significant association of age with adiponectin was a result of changes accrued in body composition ,.
In this study, WHR was significantly higher in group A than control group, but waist circumference, hip circumference, and WHR were significantly higher in group B than control group. Similar finding was observed by Donato et al. , who found that, compared with postmenopausal women, the premenopausal women were usually taller with thinner waist circumference and had lower WHR, which is because postmenopausal women had a chance of having central adiposity than premenopausal women by five times even after BMI controlling.
Moreover, there was a significantly difference among the three groups in serum calcium, serum phosphorus, and PTH. In this study, serum Ca was significantly lower in group A than control group. However, the mean value of serum phosphorus was significantly higher in group B than control group. In addition, serum Ca was significantly lower in group B than control group. Moreover, the mean value of serum Ca was significantly lower in group A than group B, whereas the serum phosphorous was significantly higher in group A than group B.
McNair et al.  have shown that serum calcium and PTH are slightly lower in diabetics than in controls. Moreover, Khosla et al.  found that serum PTH was significantly increased when the premenopausal women and the untreated postmenopausal women were analyzed (P < 0.001).
This result was inconsistent with a previous study by Sachdeva et al. , which showed that serum calcium has no significant role in osteoporosis diagnosis.
In this study, the mean value of FBG and CRP was significantly higher in group A than control group and the mean value of FBG and CRP was significantly higher in group B than control group. Moreover, the mean value of FBS and CRP was significantly lower in group A than group B. The mechanism for CRP to get involved in the diabetic microangiopathy is that through insulin resistance process, CRP participates in the development of diabetic microangiopathy, it produces stimulus via complement, and it causes damage to endothelial cells . In contrast, Ebong et al. , found that CRP levels were lower in premenopausal when compared with premenopausal women.
On the contrary, serum TSH was significantly lower in group A and group B than control group, and the serum TSH was significantly higher in group A than group B. Elevated serum TSH is common in postmenopausal women, and clinical symptoms caused by abnormal thyroid function could be masked by postmenopausal symptoms. It is known that estrogen influences serum thyroid hormone by increasing the level of thyroxine-binding globulin, with the decrease of its clearance .
The main finding of this study is that serum adiponectin correlates negatively with lumbar BMD in osteoporotic postmenopausal women. By contrast, no significant correlation was found in the other groups. This study differs from previous studies in that it was conducted on a population of the same age group, sex, and menopausal state. Lenchik et al.  showed that serum adiponectin was inversely correlated with BMD, whereas Tamura et al.  revealed that there was a significant positive association between serum adiponectin level in Japanese patients. Although they studied men and women together, it is well known that adiponectin concentration differs between men and women .
Therefore, it would be more suitable to perform studies on adiponectin after separating between men and women to minimize such sex-related differences.
In our study, serum adiponectin level was higher in group A than control group and lower in group B than control group. In patients with osteoporosis, a possible explanation was that serum adiponection level is reactively elevated during its up-regulated synthesis and secretion which protect the bone from osteopenia and osteoporosis. Moreover, diabetic patients have an excess of insulin, which has an anabolic effect on bone by interacting with the IGF-1 receptor present on osteoblasts, which resulted in that the lumbar BMD of diabetic osteoporotic patients was significantly lower than that of the control group and higher than the BMD of the nondiabetic osteoporotic women 
Similarly, the study by Jurimae and Jürimäe  demonstrated that adiponectin is inversely associated with BMD and plasma adiponectin concentration was significantly related to age (r = 0.48 and P < 0.05), WHR (r=−0.26 and P < 0.05), total BMD (r=−0.26 and P < 0.05), and lumbar spine BMD (r=−0.31 and P < 0.05).
However, other investigators have shown that there was no independent relationship between adiponectin and BMD. Thus, the clear association between adiponectin and BMD remains unclear ,.
Some interesting relationships between the level of bone turnover markers and adiponectin levels were shown by Sodi et al. , as they found no significant difference in adiponectin level between postmenopausal women with or without osteoporosis, which may indicate an absence of effect of adiponectin on osteoporotic changes.
The debate in the evaluation of the role of adiponectin on bone remodeling is continuously increasing. For example, Jürimäe et al.  observed that the circulating adiponectin had an independent role in the development of BMD in perimenopausal women and may represent a link between adipose tissue and BMD. Human studies have demonstrate that circulating adiponectin level has an inverse relation with BMD .
This study has some limitations: we analyzed only participants who visited our center, so the make up of our patients might not be representative. The sample size was small and makes our results not enough to build clear-cut conclusions. For this reason, assessment of larger population was recommended. Finally, although we measure the lumbar BMD which is considered as the most represented and precise indicator of BMD, more studies need to be done to measure other areas, as the hip bone or the femur.
| Conclusion|| |
Our findings confirmed that the serum adiponectin has a role in bone metabolism and may be used as an indicator of the lumbar BMD and is considered as a dependent predictor of BMD in postmenopausal, as a marker of bone turnover owing to its role as a negative regulator for bone mass by enhancing bone resorption in postmenopausal women.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Cho N, Shaw J, Karuranga S, Huang Y, da Rocha Fernandes J, Ohlrogge A, et al
. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138
Scheller EL, Burr AA, MacDougald OA, Cawthorn WP. Inside out: bone marrow adipose tissue as a source of circulating adiponectin. Adipocyte 2016; 5
Al-Osami MH, Hameed EK. Serum adiponectin level in osteoporotic postmenopausal women with type 2 diabetes mellitus. Diabetes Metab Syndr 2018; 12
Bauer DC, Browner WS, Cauley JA, Orwoll ES, Scott JC, Black DM, et al
. Factors associated with appendicular bone mass in older women. Ann Intern Med 1993; 118
Felson DT, Zhang Y, Hannan MT, Anderson JJ. Effects of weight and body mass index on bone mineral density in men and women: the Framingham study. J Bone Miner Res 1993; 8
Nordin B, Need AG, Bridges A, Horowitz M. Relative contributions of years since menopause, age, and weight to vertebral density in postmenopausal women. J Clin Endocr Metab 1992; 74
Bik W, Baranowska-Bik A, Wolinska-Witort E, Martynska L, Chmielowska M, Szybinska A, et al
. The relationship between adiponectin levels and metabolic status in centenarian, early elderly, young and obese women. Neuroendocrinol Lett. 2006; 27
Kanaley J, Sames C, Swisher L, Swick A, Ploutz-Snyder L, Steppan C, et al
. Abdominal fat distribution in pre-and postmenopausal women: the impact of physical activity, age, and menopausal status. Metabolism 2001; 50
Lenchik L, Register T, Hsu F, Lohman K, Nicklas B, Freedman B, et al
. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone 2003; 33
Sieminska L, Wojciechowska C, Niedziolka D, Marek B, Kos-Kudla B, Kajdaniuk D, et al
. Effect of postmenopause and hormone replacement therapy on serum adiponectin levels. Metabolism 2005; 54
Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al
. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol 2005; 153
Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al
. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289
Jürimäe J, Rembel K, Jürimäe T, Rehand M. Adiponectin is associated with bone mineral density in perimenopausal women. Horm Metab Res 2005; 37
Gavrila A, Chan JL, Yiannakouris N, Kontogianni M, Miller LC, Orlova C, et al
. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocr Metab 2003; 88
Cnop M, Havel P, Utzschneider K, Carr D, Sinha M, Boyko E, et al
. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003; 46
Donato GB, Fuchs SC, Oppermann K, Bastos C, Spritzer PM. Association between menopause status and central adiposity measured at different cutoffs of waist circumference and waist-to-hip ratio. Menopause 2006; 13
McNair P, Madsbad S, Christiansen C, Christensen MS, Transbøl I. Hyponatremia and hyperkalemia in relation to hyperglycemia in insulin-treated diabetic out-patients. Clin Chim Acta 1982; 120
Khosla S, Atkinson EJ, Melton LJIII, Riggs BL. Effects of age and estrogen status on serum parathyroid hormone levels and biochemical markers of bone turnover in women: a population-based study. J Clin Endocr Metab 1997; 82
Sachdeva A, Seth S, Khosla AH, Sachdeva S. Study of some common biochemical bone turnover markers in postmenopausal women. Indian J Clin Chem 2005; 20
Chunlian C, Yufang Y, Zhicheng W. Study of the correlation between serum chemerin and C-reactive protein levels of type-2 diabetic patients and insulin-resistance and macroangiopathy. J Chin Gen Pract 2013; 16
Ebong IA, Schreiner P, Lewis CE, Appiah D, Ghelani A, Wellons M. The association between high-sensitivity C-reactive protein and hypertension in women of the CARDIA study. Menopause 2016; 23
Mazer NA. Interaction of estrogen therapy and thyroid hormone replacement in postmenopausal women. Thyroid 2004; 14
Tamura T, Yoneda M, Yamane K, Nakanishi S, Nakashima R, Okubo M, et al
. Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus. Metabolism 2007; 56
Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, et al
. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279
Jurimae J, Jürimäe T. Plasma adiponectin concentration in healthy pre-and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables. Am J Physiol Endocrinol Metab 2007; 293
Huang KC, Cheng WC, Yen RF, Tsai KS, Tai TY, Yang WS. Lack of independent relationship between plasma adiponectin, leptin levels and bone density in nondiabetic female adolescents. Clin Endocrinol 2004; 61
Kontogianni MD, Dafni UG, Routsias JG, Skopouli FN. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res 2004; 19
Sodi R, Hazell M, Durham B, Rees C, Ranganath L, Fraser W. The circulating concentration and ratio of total and high molecular weight adiponectin in post-menopausal women with and without osteoporosis and its association with body mass index and biochemical markers of bone metabolism. Clin Biochem 2009; 42
[Table 1], [Table 2]