Insulin therapy in patients with type 2 diabetes and high insulin resistance is associated with increased risk of complications and mortality

ABSTRACT

Objective: To investigate the relationship between insulin use and clinical outcomes in patients with type 2 diabetes stratified by level of insulin resistance (IR).

Methods: Cross sectional analysis of the NHANES database from 2001 to 2010. Sample was comprised of 3,124 individuals with diabetes, representing a US population of 16,713,593. Insulin use was self-reported. Fasting glucose and insulin levels were used to assess IR by HOMA-IR determination. Subjects were allocated within High or Low HOMA-IR groups based on the sample median. Outcome variables were mortality, major adverse cardiovascular events (MACE), and diabetic kidney disease (DKD). Logistic regression adjusting for covariates including glycemic control and comorbidities were performed.

Results: In the adjusted model, insulin use was significantly associated with increased risk of mortality (OR: 2.39, 95% CI: 1.136–5.010) having a MACE (OR: 2.45, 95% CI: 1.137–4.550), and developing DKD (OR: 1.89, 95% CI: 1.119–3.198) in the high HOMA-IR group. The association between insulin use and the outcome variables was not statistically significant in patients within the low HOMA-IR group.

Conclusions: Insulin use was associated with increased risk of mortality, MACE, and DKD in patients within the high IR group, but the association was not significant within the low IR group. Our findings indicate that insulin therapy could be less beneficial in patients with high IR. Prospective studies are needed to identify subsets of individuals with type 2 diabetes who would benefit the most from insulin therapy, and for which patients, insulin should be avoided.

KEYWORDS:

• Insulin therapy
• exogenous insulin
• insulin resistance
• metabolic syndrome
• hyperinsulinemia
• cardiovascular disease
• diabetic nephropathy
• mortality
• outcomes

Acknowledgments

Effort for this study was partially supported by the National Institute of Diabetes and Digestive Kidney Disease (K24DK093699, R01DK118038, R01DK120861, PI: Egede), the National Institute for Minority Health and Health Disparities (R01MD013826, PI: Egede/Walker), and the American Diabetes Association (1-19-JDF-075, PI: Walker). No potential conflicts of interest relevant to this article were reported. C.E.M. designed the study and wrote the manuscript. R.J.W. analyzed the data and wrote the manuscript. C.R.E. analyzed the data and wrote the manuscript. B.M.M. contributed to the design of the study and wrote the manuscript. L.E.E. contributed to the design, analysis, critical review, and edited the manuscript. C.E.M. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Parts of this study were presented as a poster presentation at the 78nd Scientific Sessions of the American Diabetes Association, Orlando, Florida, 20–26 June 2018. The authors would like to acknowledge Dr. Robert J. Tanenberg (recently deceased) for his invaluable support in the conception of this study and for his vast contributions to the field of diabetes care throughout his career.

Declaration of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This paper was not funded.