Serum Prolactin, Glycemic Control, and Insuline Resistance in Type 2 Diabetes in Iraq: A Sex-Stratified Cross-Sectional Comparative Studay

Huda Shareef  Diab

doi:10.51699/cajmns.v7i4.3385

Authors

Huda Shareef Diab Department of Science, Faculty of Basic Education-Al-Shirqat, Tikrit University, Salah Aldin, 34005, Iraq

DOI:

https://doi.org/10.51699/cajmns.v7i4.3385

Keywords:

Prolactin, Type 2 Diabetes Mellitus, Glycemic Control, Insulin Resistance, Sex Differences, Iraq

Abstract

Type 2 diabetes mellitus (T2DM) represents an increasing health burden in Iraq. Prolactin (PRL) is involved in the regulation of glucose metabolism since high PRL serum levels are associated with low incidence of T2DM. This study evaluated the relationship between serum prolactin levels and key indicators of glycemic control and insulin resistance in T2DM patients, with a dedicated sex disaggregated analysis. A comparative cross-sectional study was conducted in Salahaddin Governorate, Iraq. The study included 60 participants: 30 patients with T2DM and 30 healthy individuals of the same age group (15 males and 15 females) aged between 20 and 60 years. All participants underwent baseline assessment (age and Body mass index (BMI)) and five vital signs (Fasting blood glucose (FBG), fasting insulin, glycated hemoglobin, insulin resistance index, and prolactin). All statistical analyses were performed using IBM SPSS Statistics software for Windows. The level of statistical significance was set at p < 0.05. Body mass index did not differ between the groups (P > 0.05). However, the patients were significantly older than the control group overall (p = 0.002 and p = 0.006, respectively). The patient group recorded higher fasting blood glucose and glycated hemoglobin (HbA1c) values compared to the control group in the overall sample (P < 0.05). At the correlation level, prolactin was associated with fasting blood glucose (r = 0.31, P = 0.013) and HbA1c (r = 0.35, P = 0.005) in the overall sample; while a non-statistically significant correlation was observed with the insulin resistance index (r = 0.24, P = 0.059), and no statistically significant correlation was found with fasting insulin. None of the sex-specific subgroup correlations were statistically significant. Prolactin shows a statistically significant positive association with palm-expressed FBG and HbA1c at the aggregate level when controlling for age difference between groups. Importantly, however, this association did not reach significance in the sex stratified subanalyses. Although this observation is a preliminary one, it should be confirmed in larger, broader powered studies specifically designed to explore sex dependent metabolic effects.

References

Magliano, D. J., & Boyko, E. J. (2025). The global picture of diabetes. In International Diabetes Federation, Diabetes atlas (11th ed., Chapter 3). International Diabetes Federation. https://www.ncbi.nlm.nih.gov/books/NBK618744/

Mansour, A. A., Al-Maliky, A. A., Kasem, B., Jabar, A., & Mosbeh, K. A. (2014). Prevalence of diagnosed and undiagnosed diabetes mellitus in adults aged 19 years and older in Basrah, Iraq. Diabetes, metabolic syndrome and obesity: targets and therapy, 139-144. https://doi.org/10.2147/DMSO.S59652

Abusaib, M., Ahmed, M., Nwayyir, H. A., Alidrisi, H. A., Al-Abbood, M., Al-Bayati, A., ... & Mansour, A. (2020). Iraqi experts consensus on the management of type 2 diabetes/prediabetes in adults. Clinical Medicine Insights: Endocrinology and Diabetes, 13, 1179551420942232. https://doi.org/10.1177/1179551420942232

Rashad, B., Hussein, N. R., Dirbas, V. H., & Naqid, I. A. (2025). Prevalence and determinants of undiagnosed diabetes mellitus among adults in Zakho City, Kurdistan Region, Iraq: A community-based cross-sectional study. Cureus, 17(1). https://doi.org/10.7759/cureus.77618

DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., ... & Weiss, R. (2015). Type 2 diabetes mellitus. Nature reviews Disease primers, 1(1), 15019.‏ https://doi.org/10.1038/nrdp.2015.19

American Diabetes Association Professional Practice Committee. (2024). 2. Diagnosis and classification of diabetes: standards of care in diabetes—2024. Diabetes care, 47(Suppl 1), S20.‏ https://doi.org/10.2337/dc24-S002

Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. (1985). Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. diabetologia, 28(7), 412-419.‏ https://doi.org/10.1007/BF00280883

Kautzky-Willer, A., Leutner, M., & Harreiter, J. (2023). Sex differences in type 2 diabetes. Diabetologia, 66(6), 986-1002. https://doi.org/10.1007/s00125-023-05891-x

Kautzky-Willer, A., Harreiter, J., & Pacini, G. (2016). Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocrine reviews, 37(3), 278-316. https://doi.org/10.1210/er.2015-1137

Blandine, T., Sarra, S., Naia, G., Françoise, L., Jean-François, A., Montagner, A., & Pierre, G. (2020). Sex differences in metabolic regulation and diabetes susceptibility. Diabetologia, 63(3), 453-461. https://doi.org/10.1007/s00125-019-05040-3

Karaca, Z., Unluhizarci, K., & Kelestimur, F. (2024). Hypoprolactinemia. Does it matter? Redefining the hypopituitarism and return from a mumpsimus: “Absence of proof is not the proof of absence”. Reviews in Endocrine and Metabolic Disorders, 25(6), 943-951. https://doi.org/10.1007/s11154-023-09847-9

Grattan, D. (2015). 60 years of neuroendocrinology. the hypothalamo-prolactin axis.Journal of Endocrinol , 226 (2),T101–T122. https://doi.org/10.1530/JOE-15-0213

Bernard, V., Young, J., & Binart, N. (2019). Prolactin—a pleiotropic factor in health and disease. Nature Reviews Endocrinology, 15(6), 356-365. https://doi.org/10.1038/s41574-019-0194-6

Wu, T., Duan, Y., Jiang, J., Gu, T., Zhang, P., & Bi, Y. (2024). A century of prolactin: emerging perspectives as a metabolic regulator. Diabetes/metabolism research and reviews, 40(6), e3836. https://doi.org/10.1002/dmrr.3836

Scairati, R., Auriemma, R. S., Del Vecchio, G., Di Meglio, S., Pivonello, R., & Colao, A. (2024). Prolactin effects on the pathogenesis of diabetes mellitus. European Journal of Clinical Investigation, 54(6), e14190. https://doi.org/10.1111/eci.14190

Zenaw, A., Chane, E., Fetene, G., Admas, S., Alemu, N., Tigabie, M., ... & Worede, A. (2025). Serum prolactin level in male type 2 diabetes mellitus patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2024. Scientific Reports, 16(1), 2570. https://doi.org/10.1038/s41598-025-32477-x

Jayashankar, C. A., Manohar, A., Joshi, A., Dwarakanathan, V., Pinnelli, V. B. K., Sarathi, V., ... & Pinnelli, V. B. (2022). Association of serum prolactin with type 2 diabetes mellitus: a comparative cross-sectional study from South India. Cureus, 14(4). https://doi.org/10.7759/cureus.23721

Shah, P., Nankova, B. B., Parab, S., & La Gamma, E. F. (2006). Short chain fatty acids induce TH gene expression via ERK-dependent phosphorylation of CREB protein. Brain research, 1107(1), 13-23.

Pirchio, R., Graziadio, C., Colao, A., Pivonello, R., & Auriemma, R. S. (2022). Metabolic effects of prolactin. Frontiers in endocrinology, 13, 1015520.https://doi.org/10.3389/fendo.2022.1015520‏

Kwon, S. K. (2014). Women are diagnosed with type 2 diabetes at higher body mass indices and older ages than men: Korea national health and nutrition examination survey 2007-2010. Diabetes & Metabolism Journal, 38(1), 74-80. https://doi.org/10.4093/dmj.2014.38.1.74‏

Ciarambino, T., Crispino, P., Guarisco, G., & Giordano, M. (2023). Gender differences in insulin resistance: new knowledge and perspectives. Current issues in molecular biology, 45(10), 7845-7861.‏ https://doi.org/10.3390/cimb45100496

Yan, H., Yang, W., Zhou, F., Li, X., Pan, Q., Shen, Z., ... & Guo, S. (2019). Estrogen improves insulin sensitivity and suppresses gluconeogenesis via the transcription factor Foxo1. Diabetes, 68(2), 291-304.‏ https://doi.org/10.2337/db18-0638

Wagner, R., Heni, M., Linder, K., Ketterer, C., Peter, A., Böhm, A., ... & Fritsche, A. (2014). Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans. Acta diabetologica, 51(1), 71-78. ‏https://doi.org/10.1007/s00592-013-0493-7

Aga, I. M. A., & Al-Naemi, A. H. (2025). Prevalence of Type 2 Diabetes Mellitus and Pre-Diabetes in Mosul City, Northern Iraq: Changes over 20 years!. Ann Coll Med Mosul June, 47(1), 13-20 . https://doi.org/10.33899/mmed.2025.157150.1303

Balbach, L., Wallaschofski, H., Völzke, H., Nauck, M., Dörr, M., & Haring, R. (2013). Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes? BMC endocrine disorders, 13(1), 12.‏ https://doi.org/10.1186/1472-6823-13-12

Qian, Q., Qian, H., Zhang, X., Zhu, W., Yan, Y., Ye, S., ... & Xu, W. (2012). 5-Azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase. Stem cells and development, 21(1), 67-75.‏

Macotela, Y., Triebel, J., & Clapp, C. (2020). Time for a new perspective on prolactin in metabolism. Trends in Endocrinology & Metabolism, 31(4), 276-286. ‏https://doi.org/10.1016/j.tem.2020.01.004

Rashed, H. M., El-Ghlban, S., Mahfouz, M. K., & Marie, Y. M. A. R. (2025). Hyperprolactinemia alters insulin resistance profiles in overweight males. Endocrine Regulations, 59(1), 160-166. https://doi.org/10.2478/enr-2025-0018

Gierach, M., Bruska-Sikorska, M., Rojek, M., & Junik, R. (2022). Hyperprolactinemia and insulin resistance. Endokrynologia Polska, 73(6), 959-967. https://doi.org/10.5603/EP.a2022.0075

Yanachkova, V., & Stankova, T. (2025). Abnormally increased prolactin levels in women with polycystic ovarian syndrome are associated with risk of obesity, insulin resistance and prediabetes. International Journal of Molecular Sciences, 26(9), 4239.‏ https://doi.org/10.3390/ijms26094239

Zhu, C., Ma, H., Huang, D., Li, G., Gao, J., Cai, M., ... & Qu, S. (2022). J-shaped relationship between serum prolactin and metabolic-associated fatty liver disease in female patients with type 2 diabetes. Frontiers in Endocrinology, 13, 815995.‏ https://doi.org/10.3389/fendo.2022.815995

Al-Nami, M. S., Al-Kuraishy, H. M., Al-Gareeb, A. I., & Al-Mamoori, F. (2019). Metabolic profile and prolactin serum levels in men with type 2 diabetes mellitus: old-new rubric. International journal of critical illness and injury science, 9(3), 120.‏ https://doi.org/10.4103/IJCIIS.IJCIIS_40_19

Ben-Jonathan, N., Hugo, E. R., Brandebourg, T. D., & LaPensee, C. R. (2006). Focus on prolactin as a metabolic hormone. Trends in Endocrinology & Metabolism, 17(3), 110-116. https://doi.org/10.1016/j.tem.2006.02.005 ‏

Rasheed, H. A., Al-Kuraishy, H. M., Al-Gareeb, A. I., Hussien, N. R., & Al-Nami, M. S. (2019). Effects of diabetic pharmacotherapy on prolactin hormone in patients with type 2 diabetes mellitus: Bane or Boon. Journal of advanced pharmaceutical technology & research, 10(4), 163. https://doi.org/10.4103/japtr.japtr_65_19