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

Postgrad Med. 2019 Aug;131(6):376-382. doi: 10.1080/00325481.2019.1643635. Epub 2019 Jul 23.


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; cardiovascular disease; diabetic nephropathy; exogenous insulin; hyperinsulinemia; insulin resistance; metabolic syndrome; mortality; outcomes.

MeSH terms

  • Age Factors
  • Aged
  • Blood Glucose
  • Blood Pressure
  • Body Mass Index
  • Cardiovascular Diseases / etiology
  • Comorbidity
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetic Nephropathies / etiology
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Risk Factors
  • Sex Factors
  • Socioeconomic Factors


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin