Gender Differences Regarding Novel Biomarkers and Metabolic Risk Factors in Metformin Treated Type 2 Diabetic Patients

Per E. Wandell*, 1, Bruna Gigante2, Anna Nixon Andreasson1, 3, Axel C. Carlsson1, 4
1 Center for Family and Community Medicine, Karolinska Institutet, Huddinge, Sweden.
2 Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden/
3 Stress Research Institute, Stockholm University, Stockholm, Sweden.
4 Department of Public Health and Caring Sciences/Section of Geriatrics, Uppsala University, Uppsala, Sweden.

© E. Wandell et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Center for Family and Community Medicine, Karolinska Institutet, Alfred Nobels Alle 12, S-141 83 Huddinge, Sweden. Tel: +46-8-52488727; Fax: +46-8-52488706; E-mail:


We aimed to analyze associations between adiponectin, ghrelin and leptin with anthropometric and metabolic markers in men and women with Metformin-treated type 2 diabetes (n=53), recruited from a trial of relaxation therapies. Anthropometrical measures and fasting blood samples were assessed on three occasions: at baseline, and after 10 and 24 weeks: BMI, waist, HbA1c, insulin, glucose, adiponectin, leptin, fasting ghrelin, high sensitivity C-reactive protein (CRP), tumor necrosis factor α (TNF- α) and interleukin 6 (IL-6). HOMA2ir and HOMA2s were calculated from fasting glucose and insulin, and adiponectin/leptin and adiponectin/HOMA2ir ratios were calculated. In men, higher leptin and lower adiponectin/leptin ratio correlated with insulin and insulin resistance, and in women lower ghrelin with insulin and insulin resistance. In multivariate linear regression, higher levels of leptin were associated with insulin resistance among men, but not among women. Among women, insulin resistance was associated with lower adiponectin/leptin ratio and ghrelin. Factor analysis showed that leptin in women was closely related to anthropometric variables, but in men both related to anthropometric and inflammatory variables. Gender differences could indicate different pathophysiologic mechanisms of insulin resistance and type 2 diabetes among men and women, where leptin possibly could be a better marker among men, and ghrelin among women.

Keywords: Adiponectin, factor analysis, leptin, ghrelin, insulin resistance, diabetes.