In 2021, 537 million adults were living with diabetes. Being a progressive disease, there would eventually be failure of oral hypoglycemic agents (OHA) to maintain good glycemic control and a majority will require insulin. However, optimal glycemic control has not been satisfactory in a significant proportion of patients who were on insulin therapy. Patient factors (eg, awareness, compliance, socioeconomic) have been identified but physician-related factors are as important. These include incorrect choice and inappropriate combination of insulin therapy which could be corrected by making the treatment physiologic. The purpose of this article is to improve management decisions in type 2 diabetes by reviewing its pathophysiology and identifying the optimum insulin regimen that could mimic such. Since eventual beta cell failure is central to its pathophysiology, it is but reasonable to replace insulin by mimicking its physiologic secretion. Hence, the term Insulin Replacement Therapy (IRT) should be utilized. This could be provided by the combination of premix insulin (ie, NPH + regular insulin) and rapid-acting insulin which has been reported to provide an initial 17.5% HbA1c reduction and even 18% reduction on 5-year follow-up providing sustainable control. A stepwise approach is an effective tool for insulin intensification. Hypoglycemia in insulin therapy could be prevented with an appropriate dietary regimen through automatic snacking.
Keywords: Insulin replacement therapy, type 2 diabetes mellitus, pathophysiology
- Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of diabetes by pathophysiology, Natural History, and Prognosis. Diabetes. 2017;66(2):241–55. Available from: http://dx.doi.org/10.2337/db16-0806
- Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012;27(4):269–73. Available from: http://dx.doi.org/10.5001/omj.2012.68
- Artasensi A, Pedretti A, Vistoli G, Fumagalli L. Type 2 diabetes mellitus: A review of multi-target drugs. Molecules. 2020;25(8):1987. Available from: http://dx.doi.org/10.3390/molecules25081987
- International Diabetes Federation. [Updated 2021 September 12; cited 2022 April 03]. Available from: https://idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html.
- Wong J, Yue D. Starting insulin treatment in type 2 diabetes. Aust Prescr. 2004;27(4):93–6. Available from: http://dx.doi.org/10.18773/austprescr.2004.075
- DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA. 2003;289(17):2254–64. Available from: http://dx.doi.org/10.1001/jama.289.17.2254
- Bullard KM, Cowie CC, Lessem SE, Saydah SH, Menke A, Geiss LS, et al. Prevalence of diagnosed diabetes in adults by diabetes type - United States, 2016. Morb Mortal Wkly Rep. 2018;67(12):359–61. Available from: http://dx.doi.org/10.15585/mmwr.mm6712a2
- Kalra S, Thai HQ, Deerochanawong C, Su-Yen G, Mohamed M, Latt TS, et al. Choice of insulin in type 2 diabetes: A southeast Asian perspective. Indian J Endocrinol Metab. 2017;21(3):478–81. Available from: http://dx.doi.org/10.4103/ijem.IJEM_82_17
- Chen S-Y, Hsu H-C, Wang R-H, Lee Y-J, Hsieh C-H. Glycemic control in insulin-treated patients with type 2 diabetes: Empowerment perceptions and diabetes distress as important determinants. Biol Res Nurs. 2019;21(2):182–9. Available from: http://dx.doi.org/10.1177/1099800418820170
- Blonde L, Aschner P, Bailey C, Ji L, Leiter LA, Matthaei S, et al. Gaps and barriers in the control of blood glucose in people with type 2 diabetes. Diab Vasc Dis Res. 2017;14(3):172–83. Available from: http://dx.doi.org/10.1177/1479164116679775
- Normal Glucose Metabolism. [Updated 2022; cited 2022 April 6] Available from: https://www.diabeteseducatorscalgary.ca/other/diabetes-overview/pathophysiology-of-diabetes.html#sppb-tab2-3.
- Thompson R, Christie D, Hindmarsh PC. The role for insulin analogues in diabetes care. Curr paediatr. 2006;16(2):117–22. Available from: http://dx.doi.org/10.1016/j.cupe.2005.12.011
- Wysham C, Shubrook J. Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications. Postgrad Med. 2020;132(8):676–86. Available from: http://dx.doi.org/10.1080/00325481.2020.1771047
- Phillips LS, Ratner RE, Buse JB, Kahn SE. We can change the natural history of type 2 diabetes. Diabetes Care. 2014;37(10):2668–76. Available from: http://dx.doi.org/10.2337/dc14-0817
- Hanefeld M, Fleischmann H, Siegmund T, Seufert J. Rationale for timely insulin therapy in type 2 diabetes within the framework of individualised treatment: 2020 update. Diabetes Ther. 2020;11(8):1645–66. Available from: http://dx.doi.org/10.1007/s13300-020-00855-5
- Donner T, Sarkar S. Insulin - Pharmacology, Therapeutic Regimens, and Principles of Intensive Insulin Therapy. [Updated 2019 Feb 23; cited 2022 April 06]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278938/
- Hodish I. Insulin therapy for type 2 diabetes – are we there yet? The d-Nav® story. Clin Diabetes Endocrinol . 2018;4(1):1–11. Available from: http://dx.doi.org/10.1186/s40842-018-0056-5
- Fekadu G, Bula K, Bayisa G, Turi E, Tolossa T, Kasaye HK. Challenges and factors associated with poor glycemic control among type 2 diabetes mellitus patients at Nekemte Referral Hospital, western Ethiopia. J Multidiscip Healthc. 2019;12:963–74. Available from: http://dx.doi.org/10.2147/JMDH.S232691
- A Kakade A, R Mohanty I, Rai S. Assessment of factors associated with poor glycemic control among patients with Type II diabetes mellitus. Integr Obes Diabetes. 2018;4(3):1–6. Available from: http://dx.doi.org/10.15761/iod.1000209
- Tong WT, Vethakkan SR, Ng CJ. Why do some people with type 2 diabetes who are using insulin have poor glycaemic control? A qualitative study. BMJ Open. 2015;5(1):e006407. Available from: http://dx.doi.org/10.1136/bmjopen-2014-006407
- Motilal S. Physician related barriers towards insulin therapy at primary care centres in Trinidad: a cross-sectional study. BMC Fam Pract. 2020;21(1):197. Available from: http://dx.doi.org/10.1186/s12875-020-01271-1
- Freeman JS. Insulin analog therapy: improving the match with physiologic insulin secretion. J Am Osteopath Assoc. 2009;109(1):26–36. PMID: 19193822.
- Diabetes Educators [Internet]. Pathophysiology of Diabetes Mellitus Type 2. [Updated 2022; cited 2022 April 06] Available from: Diabeteseducatorscalgary.ca
- Laplano NE, Quiambao DA, Uy J, Mercado-Asis LB. Combination Insulin Therapy with Pre-Mixed Intermediate/Rapid-Acting Insulin (70/30) and Insulin Lispro Mimicking Physiologic Insulin Secretion: Optimal Glycemic Treatment with Sustainability of Control in type 2 Diabetic Patients. Philippine Journal Internal Medicine. 2009;47:93–7. Available from: doi 10.3860/PJIM.V47I3.1650
- Laplano NE, Asis LM. Sustainable Glycemic Control with Combination Insulin Therapy of Biphasic Insulin Plus Rapid-Acting Insulin Mimicking Physiologic Insulin Secretion in Type 2 Diabetes. Philippine Journal Internal Medicine 2012;50. Available from: DOI:10.1210/endo-meetings.2011.PART2.P10.P1-536
- Lopez AA, Mercado-Asis LB. Treatment Outcomes with the Use of a Stepwise Insulin Combinations Algorithm Among Type 2 Diabetic Patients. Philippine Journal Internal Medicine. 2016;54. Available from: https://www.researchgate.net/publication/306147033
- Yun J-S, Park Y-M, Han K, Cha S-A, Ahn Y-B, Ko S-H. Severe hypoglycemia and the risk of cardiovascular disease and mortality in type 2 diabetes: a nationwide population-based cohort study. Cardiovasc Diabetol. 2019;18(1):103. Available from: http://dx.doi.org/10.1186/s12933-019-0909-y
- Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59. Available from: http://dx.doi.org/10.1056/NEJMoa0802743
- Huang ES, Laiteerapong N, Liu JY, John PM, Moffet HH, Karter AJ. Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study: The diabetes and aging study. JAMA Intern Med. 2014;174(2):251–8. Available from: http://dx.doi.org/10.1001/jamainternmed.2013.12956
- Lorenzo ZG, Mercado-Asis LB. Automatic Snacking Prevents Hypoglycemia Among Outpatient Type 2 Diabetic Patients on Intensive Insulin Therapy. Philippine Journal Internal Medicine. 2011;49(2). Available from: https://www.researchgate.net/publication/290613381
- Cukierman-Yaffe T, Gerstein HC, Williamson JD, Lazar RM, Lovato L, Miller ME, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009;32(2):221–6. Available from: http://dx.doi.org/10.2337/dc08-1153
- Valdez MNR, Mercado-Asis LB, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines. Long term evaluation of intensive insulin therapy in patients with type 2 diabetes mellitus. Series Endo Diab Met. 2021;2(3):88–94. Available from: http://dx.doi.org/10.54178/jsedmv2i3002
- Mercado-Asis LB, Section of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines. Cardiovascular adverse outcomes as challenges on glycemic variability among patients with type 2 diabetes on intensive insulin therapy: The role of medical nutrition therapy with automatic snacking. Series Endo Diab Met. 2021;3(2):59–68. Available from: http://dx.doi.org/10.54178/jsedmv3i2004
Articles related to the one you are viewing
There are currently no results to show, please try again later
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits use, share — copy and redistribute the material in any medium or format, adapt — remix, transform, and build upon the material, as long as you give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. If you remix, transform, or build upon the material, you must distribute your contributions under the same license as the original. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/4.0/.