In this nationwide study of 266,305 individuals with type 2 diabetes and population-based age- and sex-matched control individuals, excess risk of hospitalisation for heart failure among people with diabetes varied from mildly elevated to markedly high excess risk, particularly in younger individuals, especially younger women, and in those with poor glycaemic control, and/or impaired renal function.
Young people (<55 years) with good glycaemic control experienced a twofold excess risk, whereas those with poor glycaemic control experienced a 4.6-fold excess risk of hospitalisation for heart failure compared with control individuals. There was a successive attenuation of risk with increasing age, such that older diabetic individuals (≥75 years) with good glycaemic control experienced no (or only a slight) excess risk, and no excess risk at all in the absence of albuminuria. Similarly, there was a steady increase in excess risk with declining kidney function, whether measured as decreasing eGFR or micro- or macroalbuminuria. Here, too, the excess risk was attenuated with increasing age.
Young women with diabetes experienced an almost fivefold increased risk of hospitalisation for heart failure, while there was a twofold excess risk among young men: a greater excess risk than that seen for cardiovascular disease mortality . This was due to the overall low absolute risk in women below 55 years in the general population, but the absolute rates in women with diabetes of this age group were also lower than in men with diabetes. Absolute risk was higher in men at any age, in diabetic individuals as well as control individuals. Sex differences in both absolute and relative risks decreased with age. Both diabetes and male sex are known to be associated with increased risk of heart failure [2, 14, 15]. Our findings are in accordance with cohort studies that have demonstrated that diabetes increases the risk of heart failure more in women than in men . We are not aware of any study, however, that has quantified age-specific relative risks for heart failure associated with diabetes in men and women. Further work is needed to explain the higher relative risk for heart failure in women compared with men with diabetes. Of interest, in order to develop diabetes, women have to put on more weight than do men, and obesity is also a risk factor for heart failure .
In a previous study, we found that the excess risk of death and cardiovascular death did not persist among older individuals with type 2 diabetes after adjusting for confounders, which in part implies that preventive strategies may have succeeded to halt premature death in a large proportion of the diabetic population ; but, even so, diabetes appears to be a much more toxic condition in the young. However, when considering older individuals with diabetes, survival bias must be kept in mind, where people with a very long duration of diabetes might not survive to advanced age. Still, because we restricted our sample to individuals with a diabetes duration of <10 years, this effect would have been lessened. Our current study, however, shows that diabetes confers a near-ubiquitous but varying excess risk of heart failure in all age groups and at all levels of glycaemic control; however, not in older people in the absence of albuminuria, or whose blood glucose is well controlled. This adds important knowledge to the increasing body of evidence suggesting that heart failure is a diabetes-related complication, and adds information to prior findings of high rates of heart failure in cohorts with type 2 diabetes in the UK and the USA [3, 18].
In the group with diabetes, those with good glycaemic control were less often smokers and more frequently treated with antihypertensives, but had lower eGFR. Judging from the characteristics of the groups, we did not find any obvious confounders that might invalidate the excess risk of hospitalisation for heart failure associated with poor glycaemic control. As a group, control individuals should have had lower levels of risk factors, meaning that the independent effect of diabetes might have been overestimated. In a previous study including only people with type 2 diabetes, we showed that glycaemic control was an independent predictor of developing heart failure, even after adjusting for an array of covariates . We have also demonstrated the same association between blood glucose and risk of hospitalisation for heart failure among people with type 1 diabetes , who, as a group, do not display the same obesity-related disorders as people with type 2 diabetes.
Heart failure is a common consequence of type 2 diabetes . The association is caused by the role of diabetes as a risk factor for coronary heart disease, as well as by the often-coexisting hypertension and obesity that might accelerate heart failure, and the potential direct effects of diabetes on the myocardium. This apparent ‘diabetic cardiomyopathy’ may arise from multiple causes, including disease of the interstitium (e.g. fibrosis), as well as direct myocardial effects, including disturbances of glucose and fatty acid metabolism .
Given that heart failure is common and is associated with poor prognosis among individuals with diabetes , effective therapies are much needed. However, in a meta-analysis, no benefit on heart failure was observed with intensive vs relaxed glucose control (although these studies used older glucose-lowering drugs ), and neither has any glucose-lowering medication proven effective in preventing development of heart failure. However, the Empagliflozin, Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study reported that empagliflozin, which promotes excretion of glucose (and sodium) by inhibiting sodium–glucose cotransporter 2 (SGLT-2) in the kidneys, brought about a 34% reduction in the risk of hospitalisation for heart-failure .
The strength of the present study, in addition to having age- and sex-matched control individuals from the general population, lies in the longitudinal design, large size and national coverage of the study population, near-complete ascertainment for heart-failure hospitalisations and the presence of important covariates. To avoid possible bias in the estimation of excess risks from older management strategies and to provide data applicable to the current treatment of diabetes, we excluded individuals with diabetes duration >10 years before registration in the NDR, still generating a uniquely large sample of individuals with type 2 diabetes. However, there are also a few limitations to this study; we only assessed hospital admissions for heart failure, which means that milder cases managed in an outpatient setting were not included. However, heart-failure hospitalisation represents a well-validated and specific outcome [12, 13], and potential misclassification of heart-failure diagnoses would likely not vary by diabetes status or glycaemic control. Moreover, we did not have data on several important risk factors for the control individuals, such as blood pressure and body weight; these would have been desirable since both high BMI and hypertension lie on the causal pathway to heart failure.
In conclusion, we found that younger men and women with type 2 diabetes are at markedly high excess risk of hospitalisation for heart failure compared with age- and sex-matched control individuals. The excess risk declines with age, but persists in all age groups; however, it does not apply to the fairly large subgroup of individuals aged 75 and older with HbA1c at target level or without albuminuria. In all other individuals, the risk increases markedly with poor glycaemic control and impaired renal function. In Sweden, the prevalence of diabetes is still low at about 6% in adults , but given the steep rise in type 2 diabetes worldwide, diabetes could contribute increasingly to the global burden of early-onset heart failure.