To our knowledge, no studies to date have simultaneously analysed cardiovascular disease, heart failure, chronic kidney disease and depression as predictors of incident diabetes while also controlling for known metabolic predictors of diabetes risk. The complex interplay between cardiometabolic risk factors, such as hyperglycaemia, obesity, hypertension, dyslipidaemia and diabetes and its complications, requires a large sample with sufficient follow-up to isolate the independent contributions of each factor. In this observational cohort study of 58,056 non-diabetic patients, we found that the presence of each of these complications increased the risk of developing diabetes independently of one another and of other known risk factors.
Cardiovascular disease is recognised as an independent risk factor for diabetes . Heart failure has also been shown to increase the risk of diabetes , as has depression . Although each of these studies reported higher risks than we found, this was probably due to insufficient control for known risk factors, such as fasting glucose, or for health conditions other than those being tested. Indeed, our results were stronger in models that did not include metabolic variables or the other health conditions (data not shown). Thus, our results probably represent a more accurate estimate of the independent contributions to diabetes risk of CVD, heart failure, kidney disease and depression.
In addition to the observational study design, our study has several limitations. First, the data are limited by the inclusion of only clinic attendees who had the necessary metabolic variables measured and the opportunity for assessment of the health conditions we analysed. It is possible that non-attendees without the necessary measurements were less likely to have the studied conditions, and were also at lower risk of developing diabetes. If so, the incidence rates we report for patients without the conditions could be overestimated. However, it is also possible that the risk of developing diabetes would be unaffected if the relative relationship between the conditions studied and diabetes is the same in attendees and non-attendees. Second, we assessed the presence of CVD, heart failure, renal disease and depression at baseline. We did not attempt to account for the development of these conditions prior to diabetes onset. If patients who developed the conditions were at an elevated risk of diabetes similar to the risk in those who had the conditions at baseline, this higher risk would have been mis-assigned to those without the conditions, which would have resulted in underestimation of the relative risk. Though this is speculative, we believe that, for this reason, the relative risks of incident diabetes associated with the studied conditions are conservative. Third, patients with the studied conditions received fasting glucose tests somewhat more frequently, thereby increasing their opportunity for a diabetes diagnosis. Although our estimates adjusted for the number of follow-up tests, some unmeasured ascertainment bias might remain. Finally, our assessment of diabetes status both at baseline (as an exclusion criterion) and at follow-up (as the outcome measure) did not include oral glucose tolerance tests. Therefore, some patients with clinical diabetes but with fasting glucose <7 mmol/l were probably included in the study, while others may have developed clinical diabetes but remained undetected because of subdiagnostic fasting glucose levels. We cannot determine how this limitation would have affected our results.
Lifestyle interventions have been repeatedly shown to prevent or delay the onset of type 2 diabetes in at-risk individuals , and also improve CVD risk factors . Furthermore, the benefits of early intervention last well beyond the duration of the intervention itself [8–10]. Of course, the presence of serious comorbidities, such as those we examined, may reduce patients’ willingness or ability to engage in intensive exercise programmes. In any case, the bidirectional relationship between diabetes and its complications calls for accurate assessment of health risk well before diabetes onset so that the maximum benefits of early intervention can be realised. Furthermore, it is possible that primary prevention of CVD and other complications will reduce the risk of subsequent diabetes.