type 2 diabetes mellitus - related microvascular disease associated with incident heart failure

Last edited 07/2021 and last reviewed 08/2021

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

• pooled RR(relative risks) for heart failure associated with type 2 diabetes were 1.95 (1.70, 2.22) in women and 1.74 (1.55, 1.95) in men, with a pooled RRR of 1.09 (1.05, 1.13) (1)
• RR for individuals with diabetes vs. no diabetes was 2.06 (2)
  • summary RR was 1.23 per 20 mg/dl increase in blood glucose and there was evidence of a J-shaped association with nadir around 90 mg/dl and increased risk even within the pre-diabetic blood glucose range

Epidemiological data on the relationship between microvascular disease (MVD) with incident HF in individuals with T2DM

MVD's contribution to HF may be independent of CAD, especially as functional studies have shown an alteration of the myocardial microvasculature among individuals with diabetes mellitus in the absence of CAD (3)

• 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).
  • 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
• results:
  • 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)
  • 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.
• study authors concluded:
  • MVD was associated with an elevated risk of developing HF in adults with T2DM. This association was independent of traditional risk factors, including CAD

Reference:

• 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.
• 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.
• Kaze AD, Santhanam P, Erqou S, et al. Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus J Am Heart Assoc. 2021;10:e018998. doi: 10.1161/JAHA.120.018998.