Assessment of endocrine function in males with pre-diabetes

Ashish Agarwal; Anupama Hegde; Afzal Ahmad; Charu Yadav; Poornima A. Manjrekar; Rukmini M.S.

doi:10.51248/.v43i5.3643

Authors

Ashish Agarwal
Anupama Hegde
Afzal Ahmad
Charu Yadav
Poornima A. Manjrekar
Rukmini M.S.

DOI:

https://doi.org/10.51248/.v43i5.3643

Keywords:

HPT axis, HPA axis, HPG axis, insulin resistance, melatonin, prediabetes

Abstract

Introduction and Aim: Diabetes mellitus is associated with various endocrine derangements and prediabetes is an intermediate condition between health and full-fledged disease state. Hormones of Hypothalamus-Pituitary-Thyroid (HPT), Hypothalamus-Pituitary-Adrenal (HPA), Hypothalamus-Pituitary-Gonadal (HPG) axes and pineal gland were studied in males (n=105) with prediabetes.

Materials and Methods: Based on fasting plasma glucose (FPG), the subjects were categorized as healthy controls, prediabetes, diabetes and various hormones were compared between these three groups.

Results: Insulin levels showed a systematic increase from pre-diabetes to diabetes subjects. HPT axis had a semblance to “Primary hypothyroidism” with an increase in Thyrotropin-releasing-hormone (TRH), Thyroid-stimulating-hormone (TSH) and decrease in fT4 and fT3 with rise in glucose levels. HPA axis detected high Corticotropin Releasing Hormone (CRH), Adrenocorticotropic hormone (ACTH), cortisol in the overtly diabetic group while prediabetes values were comparable to control. The HPG axis demonstrated significantly high Gonadotropin-hormone-releasing-hormone (GnRH) in the diabetic group but not in the prediabetic. A graded increase in LH and significant decrease in testosterone and melatonin was observed with a rise in FPG.

Conclusion: Thus, it could be concluded as endocrine gland damage due to hyperglycemia and hyperinsulinemia causes multiple endocrine dysfunctions in prediabetes that aggravates, as the patient turns diabetic.

Author Biographies

Ashish Agarwal

Department of Biochemistry, NCR Institute of Medical Sciences, Meerut- Hapur Road, 245206, Uttar Pradesh, India

Anupama Hegde

Department of Biochemistry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 575004, Karnataka, India

Afzal Ahmad

Department of Biochemistry, Anugrah Narayan Magadh Medical College and Hospital, Gaya, 823001, Bihar, India

Charu Yadav

Department of Laboratory Medicine, Medanta- The Medicity, Gurugram, 122001, Haryana, India

Poornima A. Manjrekar

Department of Biochemistry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 575004, Karnataka, India

Rukmini M.S.

Department of Biochemistry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, 575004, Karnataka, India

References

Chandran, V., Rao, G.M., Rao, D. Correlation of CA 19-9 with HbA1c in prediabetic and diabetic groups. Biomedicine. 2021 Dec 31;41(4):737-741.

Lee, M., Saver, J.L., Hong, K.S., Song, S., Chang, K., Ovbiagele, B. Effect of pre-diabetes on future risk of stroke: meta-analysis. BMJ 2012; 344: 1-11.

Kalra, S. Thyroid disorders and diabetes. J Pak Med Assoc. 2014; 64(8): 966-968.

Kadiyala, R., Peter, R., Okosieme, O.E. Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract. 2010; 64(8): 1130-1139.

Andrews, R. C., Herlihy, O., Livingstone, D. E., Andrew, R., Walker, B. R. Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. J Clin Endocrinol Metab. 2002; 87(12): 5587-5593.

Colangelo, L. A., Ouyang, P., Liu, K., Kopp, P., Golden, S. H., Dobs, A. S., et al. Association of endogenous sex hormones with diabetes and impaired fasting glucose in men: multi-ethnic study of atherosclerosis. Diabetes Care. 2009; 32(6): 1049-1051.

Navarro-Alarcón, M., Ruiz-Ojeda, F. J., Blanca-Herrera, R. M., A-Serrano, M. M., Acuña-Castroviejo, D., Fernández-Vázquez, G., et al. Melatonin and metabolic regulation: a review. Food Funct. 2014;5(11): 2806-2832.

Yang, G., Li, C., Gong, Y., Fang, F., Tian, H., Li, J., et al. Assessment of insulin resistance in subjects with normal glucose tolerance, hyperinsulinemia with normal blood glucose tolerance, impaired glucose tolerance, and newly diagnosed type 2 diabetes (prediabetes insulin resistance research). Journal of Diabetes Research. 2016;2016:9270768. doi: 10.1155/2016/9270768. Epub 2015 Dec 7.

Fukushima, M., Usami, M., Ikeda, M., Nakai, Y., Taniguchi, A., Matsuura, T., et al. Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism. 2004;53(7):831-835.

Bartalena, L., Cossu, E., Grasso, L., Velluzzi, F., Loviselli, A., Cirillo, R., et al. Relationship between nocturnal serum thyrotropin peak and metabolic control in diabetic patients. The Journal of Clinical Endocrinology and Metabolism 1993; 76 (4): 983-987.

Kaur, I. , Kaur, D. , Kaur, M. , Sibia, R. P. S. , Massaon, H. K. Correlation of T3, T4, TSH with fasting plasma glucose and glycosylated haemoglobin in patients of type 2 diabetes mellitus. Int J Clin Biochem Res 2020; 7(3):338-342.

Shaikh, A.W., Memon, A.S., Sirichand. Frequency of hypothyroidism in type II diabetic patients. Pakistan J Med Health Sci 2009; 2(4): 7.

Singh, P., Khan, S., Mittal, R.K. Assessment of thyroid dysfunction in the type 2 diabetic patients. Int J Diabetes Dev Ctries 2014; 34(4): 229.

Uppal, V., Vij, C., Bedi, G.K., Vij, A., Banerjee, B.D. Thyroid disorders in patients of type 2 diabetes mellitus. Indian Journal of Clinical Biochemistry. 2013; 28(4):336-341.

Chan, O., Inouye, K., Riddell, M.C., Vranic, M., Matthews, S.G. Diabetes and the hypothalamo pituitary adrenal (HPA) axis. Minerva Endocrinol. 2003; 28: 87:102.

Hammadi, S., Chan, O., Abdellali, M., Medjerab, M., Agoun, H., Bellatreche, Z., et al. Hyperactivation of the hypothalamo pituitary adrenocortical axis in streptozotocin-diabetic gerbils (Gerbillus gerbillus). International Journal of Experimental Pathology. 2018; 99(4):172-179.

Yurii, T. Morpho functional changes of pituitary adrenal system in the long term course of experimental diabetes mellitus. J Educ Health Sport. 2016; 6(4):375-384.

Dallman, M. F., Akana, S. F., Bhatnagar, S., Bell, M. E., Choi, S., Chu, A., et al. Starvation: early signals, sensors, and sequelae. Endocrinology. 1999;140:4015-4023.

Chan, O., Chan, S., Inouye, K., Vranic, M., Matthews, S. G. Molecular regulation of the hypothalamo-pituitary-adrenal axis in streptozotocin-induced diabetes: effects of insulin treatment. Endocrinology. 2001; 142: 4872-4879.

Kamba, A., Daimon, M., Murakami, H., Otaka, H., Matsuki, K., Sato, E., et al. Association between higher serum cortisol levels and decreased insulin secretion in a general population. PLoS One. 2016 Nov 18; 11(11): e0166077.

Baccetti, B., La Marca, A., Piomboni, P., Capitani, S., Bruni, E., Petraglia, F., et al. Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality. Human Reproduction. 2002; 17(10): 2673-2677.

Roland, A.V., Moenter, S.M. Regulation of gonadotropin-releasing hormone neurons by glucose. Trends in Endocrinology & Metabolism. 2011; 22(11):443-449.

Seethalakshmi, L., Menon, M., & Diamond, D. The effect of streptozotocin-induced diabetes on the neuroendocrine-male reproductive tract axis of the adult rat. The Journal of urology. 1987; 138(1): 190-194.

Dandona, P., Rosenberg, M.T. A practical guide to male hypogonadism in the primary care setting. International journal of clinical practice. 2010; 64(6): 682-696.

Claustrat, B., Brun, J., Chazot, G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev.2005; 9(1):11-24.

Peschke, E., Bahr, I., Muhlbauer, E. Melatonin and pancreatic islets: Interrelationships between melatonin, insulin and glucagon. Int J Mol Sci. 2013; 14(4): 6981-7015.