The Framingham study showed that diabetes increases the risk of congestive heart failure (CHF) 2.4-fold in men and 5.1-fold in women. In epidemiological surveys and clinical trials, diabetics account for 10% to 30% of patients with CHF. Most are women, and they are more likely than their nondiabetic counterparts to have a history of hypertension, angina, and myocardial infarction. At the same time, CHF is itself an independent predictor of type 2 diabetes, probably because the sustained adrenergic overdrive that characterizes CHF increases both free fatty acid oxidation and insulin resistance, thus decreasing the uptake and oxidation of glucose.
Unsurprisingly, diabetes worsens prognosis in CHF. In the Studies Of Left Ventricular Dysfunction (SOLVD) Registry, which included asymptomatic patients with left ventricular dysfunction, diabetes significantly increased the risk of death and recurrent all-cause hospitalization, after adjusting for age, gender, ejection fraction, race, and etiology. Similarly, in the SOLVD trials (which included patients with overt CHF), diabetes proved a strong predictor of adverse events at follow-up in patients with CHF of ischemic origin. Further analysis of the SOLVD data showed that diabetes was the only reason for the apparently poorer prognosis of ischemic vs nonischemic CHF: outcome became unrelated to etiology once the diabetic patients were excluded.
Diabetes exacerbates morbidity in CHF. Abrupt elevation of the blood glucose can alter the osmotic balance of extracellular fluid, causing hyperosmolarity that impairs myocardial contractility. Diabetes also exacerbates comorbidity in CHF, being associated with increased rates of infection, renal dysfunction, muscle weakness, and tachyarrhythmia/bradyarrhythmia. The logical supposition that strict glycemic control, with its associated decrease in circulating fatty acids and increase in glucose oxidation, enhances outcome in diabetic CHF, has yet to be prospectively tested in a clinical trial.
The current treatment of CHF is identical in diabetics and nondiabetics. In the case of diuretics, for example, specific efficacy and safety data are lacking in diabetic CHF. Although diuretics appeared effective in the Systolic Hypertension in the Elderly Program (SHEP) trial, which included patients with diabetes and hypertension, they may interfere with insulin sensitivity; however, the effect is thought to be clinically insignificant at low doses or in combination with an angiotensin-converting enzyme (ACE) inhibitor. ACE inhibition appears particularly effective in diabetic CHF. In the Survival and Ventricular Enlargement (SAVE) trial, it was as effective in diabetics and nondiabetics. In the SOLVD trial, it was possibly even more effective, while in the Assessment of Treatment with Lisinopril And Survival (ATLAS) trial, which further confirmed the higher mortality in diabetics, ACE inhibition reduced the risk of death in diabetics by 14% vs 6% in nondiabetics. The TRAndolapril Cardiac Evaluation (TRACE) trial found that ACE inhibition decreased allcause mortality and progression to CHF in diabetics with recent myocardial infarction and left ventricular dysfunction. Yet these positive results were all obtained in subgroup analyses from large clinical trials. A dedicated study is still pending. Similarly, although angiotensin II receptor antagonists also delay progression toward cardiovascular events and nephropathy in diabetics, there as yet no data on their role in diabetic CHF.
ACE inhibitors lower insulin resistance, and their use in diabetics has been associated with hypoglycemic episodes. Frequent blood glucose monitoring is therefore advised when initiating or titrating ACE inhibitor therapy in diabetics. The same applies to potassium levels, particularly in long-standing diabetes when changes can occur in the renin-angiotensin axis, resulting in low-renin hypoaldosteronism. The results of the Randomized ALdactone Evaluation Study (RALES) have reinforced this recommendation in the event of concomitant long-term spironolactone therapy.
P-Blockers lower heart rate and free fatty acid storage, and increase glucose uptake. All these effects are considered beneficial in diabetes, and appear confirmed in diabetic CHF by the subgroup data from the MEto-prolol CR/XL (controlled release) Randomized Intervention Trial in Heart Failure (MERIT-HF) and the Multicenter Oral Carvedilol Heart failure Assessment (MOCHA) trial. However, in the absence of a dedicated prospective trial, experience remains limited.
As with diuretics and ACE inhibitors, there are theoretical reasons why p-blockers could complicate metabolic control in diabetes. Thus, with regard to fatty acid metabolism, the effects of (3-blockers in
diabetes; treatment; management; hyperglycemia; ACEI; ft-blocker; side effect; safety; prognosis