T2DM-related microvascular disease associated with incident HF

Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus

Literature - Kaze AD, Santhanam P, Erqou S, et al. - J Am Heart Assoc. 2021;10:e018998. doi: 10.1161/JAHA.120.018998.

Introductions and methods

Evidence suggests that patients with T2DM have a 2-4 fold increased risk of developing HF, independently of additional CV risk factors such as high BP, hypercholesterolemia, or CAD [1,2]. Data from animal studies suggest that microvascular dysfunction, amongst several other pathways, might link diabetes mellitus to HF [3,4]. However, epidemiological data on the relationship between microvascular disease (MVD) with incident HF in individuals with T2DM are limited. This study analyzed the association of MVD in multiple vascular beds with incident HF in patients with T2DM.

The Look AHEAD (Action of Health in Diabetes) study was a randomized, multicentered, double-blind trial that included 5145 participants from the US from August 2001 to April 2004. Inclusion criteria were: BMI ≥25 kg/m² (or ≥27 kg/m² if patients were on insulin), HbA1c ≤11%, SBP<160 mm Hg, DBP <100 mm Hg, TG levels <600 mg/dL. Individuals (45-76 years) were randomized to participate in an intensive lifestyle intervention (intervention group) or to receive diabetes mellitus support and education (control group). For the current analysis, people with a history of HF or atherosclerotic CVD defined as prior MI or stroke at baseline or with missing data on MVD were excluded. This resulted in a dataset with data from 4095 participants (mean age 58.3 [SD 6.6] years, 61.9% were women). Diabetic MVD was defined as the presence of nephropathy, retinopathy, and/or neuropathy at baseline. First hospitalization for definite or possible acute decompensated HF was prospectively assessed to determine incident HF. Median (IQR) follow-up was 9.7 (8.9-10.3) years.

Main results

  • 34.8% Of participants with T2MD had MVD at baseline. 18.2% Had nephropathy, 6.9% retinopathy, and 16.6% neuropathy.
  • After adjusting for relevant confounders, MVD was significantly associated with increased risk of incident HF in participants with T2DM (aHR 2.54, 95% CI: 1.73-3.75, P<0.001).
  • The association between MVD and incident HF remained significant after additional adjustment for interval development of CAD (aHR 2.42, 95% CI: 1.64-3.57, P<0.001).
  • Nephropathy was significantly associated with elevated risk for a first HF event (aHR 2.22, 95% CI: 1.51-3.27, P<0.001) after adjusting for traditional risk factors including CAD. The aHRs for incident HF by the presence of retinopathy and neuropathy were 1.30 (95% CI: 0.72-2.36, P=0.06) and 1.33 (95% CI: 0.86-2.07, P=0.053), respectively.


This study showed that MVD was associated with an elevated risk of developing HF in adults with T2DM. This association was independent of traditional risk factors, including CAD.


1. Ohkuma T, Komorita Y, Peters SAE, and Woodward M. Diabetes as a risk factor for heart failure in women and men: a systematic review and meta‐analysis of 47 cohorts including 12 million individuals. Diabetologia. 2019;62:1550–1560.

2. Aune D, Schlesinger S, Neuenschwander M, et al. Diabetes mellitus, blood glucose and the risk of heart failure: a systematic review and meta‐analysis of prospective studies. Nutr Metab Cardiovasc Dis 2018;28:1081-1091.

3. Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 2014;57:660–671.

4. Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. DisModel Mech. 2009;2:454–466.

Find this article online at J Am Heart Assoc

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