Influence of Metformin Dose and Treatment Adherence on Glycemic Control, Adiposity, and Cardiovascular Risk Markers in Iraqi Patients with T2DM

Zainab Abdulrahman; Mohammed Qasim Alatrakji; Ahmed Abood Al-Maliky; Khalid Ibrahim Hussein; Saad Abdulrahman Hussain

doi:10.32007/jfacmedbagdad.6441939

Authors

Zainab Abdulrahman Department of Pharmacy, Al-Kindy Teaching Hospital, Baghdad, Iraq
Mohammed Qasim Alatrakji Department of Pharmacology, College of Medicine, University of Baghdad, Baghdad, Iraq
Ahmed Abood Al-Maliky Specialized Center of Diabetes and Endocrinology, Al-Rusafa, Baghdad, Iraq
Khalid Ibrahim Hussein Specialized Center of Diabetes and Endocrinology, Al-Rusafa, Baghdad, Iraq
Saad Abdulrahman Hussain Faculty of Pharmacy, Al-Rafidain University College, Baghdad, Iraq

DOI:

https://doi.org/10.32007/jfacmedbagdad.6441939

Keywords:

Glycemic control, Metformin dose, Treatment adherence, T2DM, Visceral adiposity

Abstract

Background: Numerous factors, including metformin doses and treatment adherence, may contribute to significant variations in glycemic control and adiposity markers of type 2 diabetes (T2DM) patients.

Objectives : This study aims to determine the influence of metformin dose and treatment adherence on glycemic control and adiposity markers in Iraqi patients with T2DM.

Methods: Between October 2021 and March 2022, a case-series study at the Diabetes and Endocrinology Center – Baghdad included 153 T2DM patients with a disease duration of more than one year. Clinical and physical examinations were conducted before enrolment. We measured anthropometric variables to calculate the body mass index (BMI), waist-to-hip ratio (WHR), visceral adiposity index (VAI), and other surrogate indicators. We measured glycated hemoglobin (HbA1c), leptin, C-reactive protein (CRP), total cholesterol, HDL-c, and triglycerides in the serum.

Results: Increasing metformin doses did not improve the studied parameters. Adherence to treatment significantly influences fasting glycemia, HbA1c level, and the markers of adiposity. Meanwhile, increasing metformin doses is not associated with changes in insulin resistance and cardiovascular disease risk markers.

Conclusion: Beyond metformin dose up-titration, treatment adherence affects glycemic control, visceral adiposity, and CVD risk surrogates. Metformin dose up-titration was not linked to insulin resistance and body fat contents.

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References

Gast KB, Tjeerdema N, Stijnen T, Smit JW, Dekkers OM. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS One. 2012;7(12):e52036. doi: 10.1371/journal.pone.0052036.

Rader DJ. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med. 2007;120(3 Suppl. 1):S12-18. doi: 10.1016/j.amjmed.2007.01.003.

Reaven G. Insulin resistance and coronary heart disease in nondiabetic individuals. Arterioscler Thromb Vasc Biol. 2012;32(8):1754-1759. doi: 10.1161/ATVBAHA.111.241885.

Laakso M, Kuusisto J. Insulin resistance and hyperglycemia in cardiovascular disease development. Nat Rev Endocrinol. 2014;10(5):293-302. doi: 10.1038/nrendo.2014.29.

Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, Del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes. 2016;7(17):354-395. doi: 10.4239/wjd.v7.i17.354.

Tatoli R, Lampignano L, Bortone I, Donghia R, Castellana F, Zupo R, et al. Dietary patterns associated with diabetes in an older population from Southern Italy using an unsupervised learning approach. Sensors (Basel). 2022;22(6):2193. doi: 10.3390/s22062193.

American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of medical care in diabetes-2019. Diabetes Care. 2019;42(Suppl. 1):S90-S102. doi: 10.2337/dc19-S009.

Henry RR, Murray AV, Marmolejo MH, Hennicken D, Ptaszynska A, List JF. Dapagliflozin, metformin XR, or both: initial pharmacotherapy for type 2 diabetes, a randomized controlled trial. Int J Clin Pract. 2012;66(5):446-456. doi: 10.1111/j.1742-1241.2012.02911.x.

Maruthur NM, Gribble MO, Bennett WL, Bolen S, Wilson LM, Balakrishnan P, et al. The pharmacogenetics of type 2 diabetes: a systematic review. Diabetes Care. 2014;37:876-886. doi: 10.2337/dc13-1276.

Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: A systematic review and meta-analysis. Ann Intern Med. 2016;164(11):740-751. doi: 10.7326/M15-2650.

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. American association of clinical endocrinologists and American College of Endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21(Suppl. 1):1-87. doi: 10.4158/EP15672.GL.

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-149. doi: 10.2337/dc14-2441.

Ali MK, McKeever Bullard K, Imperatore G, Barker L, Gregg EW. Characteristics associated with poor glycemic control among adults with self-reported diagnosed diabetes--National Health and Nutrition Examination Survey, United States, 2007-2010. MMWR Suppl. 2012;61(2):32-37.

Ford ES. Trends in the control of risk factors for cardiovascular disease among adults with diagnosed diabetes: findings from the National Health and Nutrition Examination Survey 1999–2008. J Diabetes. 2011;3(4):337-347. doi: 10.1111/j.1753-0407.2011.00148.x.

American Diabetes Association. 2. Diabetes Classification and Diagnosis: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44(Suppl. 1):S15-S33. doi: 10.2337/dc21-S002.

Matthews DR, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419.

Amato MC, Giordano C, Pitrone M, Galluzzo A. Cut-off points of the visceral adiposity index (VAI) identifying a visceral adipose dysfunction associated with cardiometabolic risk in a Caucasian Sicilian population. Lipids Health Dis. 2011;10:183. doi: 10.1186/1476-511X-10-183.

Fiorentino TV, Marini MA, Succurro E, Andreozzi F, Sesti G. Relationships of surrogate indexes of insulin resistance with insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and subclinical vascular damage. BMJ Open Diabetes Res Care. 2019;7(1):e000911. doi: 10.1136/bmjdrc-2019-000911.

Zhao W, Tong JJ, Cao YT, Li JH. A linear relationship between a body shape index and risk of incident type 2 diabetes: A secondary analysis based on a retrospective cohort study in Japan. Diabetes Metab Syndr Obes. 2020;13:2139-2146. doi: 10.2147/DMSO.S256031.

Thomas DM, Bredlau C, Bosy-Westphal A, Mueller M, Shen W, Gallagher D, et al. Relationships between body roundness with body fat and visceral adipose tissue emerging from a new geometrical model. Obesity. 2013;21(11):2264–2271. doi: 10.1002/oby.20408.

Woolcott OO, Bergman RN. Relative fat mass (RFM) as a new estimator of whole-body fat percentage: A cross-sectional study in American adult individuals. Sci Rep. 2018;8(1):10980. doi: 10.1038/s41598-018-29362-1.

Abbasi F, Reaven GM. Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol. Metabolism. 2011;60(12):1673-1676. doi: 10.1016/j.metabol.2011.04.006.

World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi: 10.1001/jama.2013.281053.

Misra A, Gopalan H, Jayawardena R, Hills AP, Soares M, Reza-Albarrán AA, et al. Diabetes in developing countries. J Diabetes. 2019;11(7):522-539. doi: 10.1111/1753-0407.12913.

Deurenberg P, Deurenberg-Yap M, Guricci S. Asians are different from Caucasians and from each other in their body mass index/body fat percent relationship. Obes Rev. 2002;3:141-146. doi: 10.1046/j.1467-789X.2002.00065.x.

Jayedi A, Soltani S, Zargar MS, Khan TA, Shab-Bidar S. Central fatness and risk of all-cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies. BMJ. 2020;370:m3324. doi: 10.1136/bmj.m3324.

Lee CM, Huxley RR, Wildman RP, Woodward M. Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: a meta-analysis. J Clin Epidemiol. 2008;61:646-653. doi: 10.1016/j.jclinepi.2007.08.012.

Chang Y, Guo X, Chen Y, Guo L, Li Z, Yu S, et al. A body shape index and body roundness index: two new body indices to identify diabetes mellitus among rural populations in northeast China. BMC Public Health. 2015;15:794. doi: 10.1186/s12889-015-2150-2.

Dhana K, Kavousi M, Ikram MA, Tiemeier HW, Hofman A, Franco OH. Body shape index in comparison with other anthropometric measures in the prediction of total and cause-specific mortality. J Epidemiol Community Health. 2016;70:90-96. doi: 10.1136/jech-2014-205257.

Fujita M, Sato Y, Nagashima K, Takahashi S, Hata A. Predictive power of a body shape index for development of diabetes, hypertension, and dyslipidemia in Japanese adults: a retrospective cohort study. PLoS ONE. 2015;10:e0128972. doi: 10.1371/journal.pone.0128972.

Amato MC, Giordano C, Galia M, Criscimanna A, Vitabile S, Midiri M, et al. Visceral adiposity index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33:920e2. doi: 10.2337/dc09-1825.

Bouchi R, Asakawa M, Ohara N, Nakano Y, Takeuchi T, Murakami M, et al. Indirect measure of visceral adiposity 'A Body Shape Index' (ABSI) is associated with arterial stiffness in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2016;4:e000188. doi: 10.1136/bmjdrc-2015-000188.

Ji B, Qu H, Wang H, Wei H, Deng H. Association between the visceral adiposity index and homeostatic model assessment of insulin resistance in participants with normal waist circumference. Angiology. 2017;68:716-721. doi: 10.1177/0003319716682120.

Van der Aa MP, Elst MA, van de Garde EM, van Mil EG, Knibbe CA, van der Vorst MM. Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial. Nutr Diabetes. 2016;6(8):e228. doi: 10.1038/nutd.2016.37.