T2D: Insulin Resistance Tied to an Increased Risk of Heart Failure and Death

Pavankumar Kamat


July 02, 2021


Why this matters

  • Findings suggest that homoeostasis model assessment 2-IR (HOMA2-IR) measured at the time of T2D diagnosis may be an important additional predictor of the future risk of HF and death in patients with T2D.

Study design

  • A post hoc analysis of the UK Prospective Diabetes Study (UKPDS) included 5102 participants with newly diagnosed T2D.

  • Insulin resistance (HOMA2-IR) values were obtained from paired fasting plasma glucose and insulin measures.

  • Primary outcome: composite of incident HF or death.

  • Funding: Oxfordshire Health Services Research Committee grant.

Key results

  • Of 5102 UKPDS participants with newly diagnosed T2D, 2099 had HOMA2-IR <1.6 and 2245 had HOMA2-IR ≥1.6.

  • Over a median follow-up of 16.4 years, the composite of HF/death outcomes was reported in 1974 (45.4%) participants (235 first HF events and 1739 deaths), corresponding to an incidence rate of 29.6 per 1000 person-years.

  • A 2-fold increase in HOMA2-IR was associated with (adjusted relative risk [aRR]; 95% CI):

    • 5% greater risk of HF/death (1.05; 1.01-1.12; P=.0029); and

    • 14% greater risk of HF (1.14; 1.02-1.27; P=.017).

  • No heterogeneity was observed for the association of HOMA2-IR with HF/death between normal-weight, overweight, and obese individuals (Pinteraction=.16).

  • Over 5 years, The Kaplan-Meier survival analysis showed no between-group differences in HF event/death in participants randomly assigned to:

    • a conventional glycaemic control strategy with diet (reference group); and

    • an intensive glucose control strategy with (RR; 95% CI):

      • sulphonylurea (0.96; 0.90-1.02);

      • insulin (0.94; 0.88-1.01); and

      • metformin (0.92; 0.83-1.02; log-rank P=.24).


  • Post hoc analysis.


Wamil M, Coleman RL, Adler AI, McMurray JJV, Holman RR. Increased Risk of Incident Heart Failure and Death Is Associated With Insulin Resistance in People With Newly Diagnosed Type 2 Diabetes: UKPDS 89. Diabetes Care. 2021 Jun 23 [Epub ahead of print]. doi: 10.2337/dc21-0429. PMID: 34162666.  View abstract 

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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