Number 25, 2004
Heart failure in diabetes

Featured research

Gender differences in hypertrophy, insulin resistance and ischemic injury in the aging type 2 diabetic rat heart
Desrois M, Sidell RJ, Gauguier D, Davey CL, et al. J Mol Cell Cardiol. 2004; 37:547–555.

Patients with type 2 (noninsulin-dependent) diabetes mellitus have greater mortality after myocardial infarction and increased risk of congestive heart failure [1]. Type 2 diabetes also abolishes sex differences in premenopausal women, and women with diabetes have significantly greater mortality after myocardial infarction than men with diabetes [2]. As relationships among sex, diabetes, and susceptibility to ischemic injury have not been well documented, the aim of this study was to determine whether sex differences in cardiac insulin resistance and tolerance to ischemic injury occur in the aging type 2 diabetic rat heart. The results show that the aging hearts of female type 2 diabetic rats [Goto-Kakizaki or GK, a highly inbred strain derived from an outbred Wistar rat colony that spontaneously develops diabetes] has greater insulin resistance and greater susceptibility to ischemic injury compared with nondiabetic or male type 2 diabetic rat hearts.

Commentary
These results indicate that sex has a significant role in the development of the diabetic phenotype. Systolic blood pressure was the same in type 2 diabetic GK rats as in their sex-matched controls, suggesting that the insulin resistance was not attributable to hypertension. Decreased insulin-stimulated glucose uptake appears to be associated with cardiac hypertrophy in the type 2 diabetic GK rat heart, and the greater insulin resistance in the female GK rat hearts may be related to their increased hypertrophy, as has been suggested by others [3]. A decreased content of glucose transporter 4 protein may have contributed to the insulin resistance, but it did not explain the differences between the male and female GK rat hearts, because concentrations were decreased to the same extent in all GK rat hearts. Consequently, other mechanism(s) may be involved, such as greater abnormalities in insulin signaling in the female, compared with the male, GK rat hearts. Moreover, it was also observed that the female GK rat hearts had significantly reduced recovery of contractile function after ischemia. This may have been a result of the lower cardiac glycogen concentrations before ischemia, plus the decreased glucose uptake during ischemia, resulting in less glycolytic production of ATP in female GK rat hearts, which has been shown to underlie contracture [4]. Future studies will certainly address the important issue of possible mechanism(s) underlying the influence of sex in insulin resistance and their consequences on the development of postinfarction heart failure.

REFERENCES

Danielle Feuvray

The Association of fasting glucose levels with congestive heart failure in diabetic adults ≥65 years The Cardiovascular Health Study
Barzilay, JI, Kronmal RA, Gottdiener JS, et al. J Am Coll Cardiol. 2004;43:2236–41.

Objectives: The purpose of this study was to determine if fasting glucose levels are an independent risk factor for congestive heart failure (CHF) in elderly individuals with diabetes mellitus (DM) with or without coronary heart disease (CHD).
Background: Diabetes mellitus and CHF frequently coexist in the elderly. It is not clear whether fasting glucose levels in the setting of DM are a risk factor for incident CHF in the elderly.
Methods: A cohort of 829 diabetic participants, age≥65 years, without prevalent CHF, was followed for 5–8 years. The Cox proportional hazards modelling was used to determine the risk of CHF by fasting glucose levels. The cohort was categorised by the presence or absence of prevalent CHD.
Results: For a 1 standard deviation (60.6 mg/dL) increase in fasting glucose, the adjusted hazard ratios for incident CHF among participants without CHD at baseline with or without an incident myocardial infarction (MI) or CHD event on follow-up, was 1.41 (95% confidence interval 1.24 to 1.61; P<0.0001). Among those with prevalent CHD at baseline with or without another incident MI or CHD event on follow-up, the corresponding adjusted hazard ratio was 1.27 (95% confidence interval 1.02 to 1.58; P<0.05).
Conclusions: Among older adults with DM, elevated fasting glucose levels are a risk factor for incident CHF. The relationship of fasting glucose to CHF differs somewhat by the presence or absence or prevalent CHD

Commentary
In this study elevated fasting glucose levels in older adults were associated with an increased risk of cardiac failure. This may reflect poor adherence to therapy but the authors did not detect any difference in the use of diabetic therapy so the alternate mechanisms of impaired endothelial function and increased myocardial fibrosis and stiffness are postulated (diastolic dysfunction is a recognised problem in diabetes). In those without documented coronary heart disease (CHD) a 40% increased risk was recorded and in those with CHD it was increased by 16%.
The patients were the relatively healthy elderly and not the very ill which is of importance when considering the need for early diagnosis and treatment of diabetes. Fasting glucose was recorded and not glycated hemoglobin as an indication of diabetic control perhaps reflecting a ‘real world’ approach but it would be of interest to know the glycated hemoglobin relationship to cardiac failure.
Given that elevated fasting glucose levels in subjects over 65 years of age are associated with an increased risk of cardiac failure it is important to know if better glucose control can reduce the risk and whether metabolic drug therapy early in the diagnosis may also be of benefit.

Graham Jackson