The impact of metabolic control and QTc prolongation on all-cause mortality in patients with type 2 diabetes and foot ulcers

Abstract

Aims/hypothesis The increased all-cause mortality in patients with chronic diabetic foot ulcers cannot fully be explained by traditional cardiovascular risk factors. The significance of heart-rate-corrected QT (QTc) prolongation, a finding often seen in these patients, is unknown. Recently, the importance of metabolic control and hypoglycaemia has been discussed. The aim of this study was to evaluate the impact of different HbA 1c levels and QTc prolongation on all-cause mortality in the high-risk population of patients with type 2 diabetes mellitus and foot ulcers. Methods All patients with type 2 diabetes, younger than 80 years, visiting our diabetes foot unit, with a foot ulcer duration >4 weeks, were screened for participation. Patients on dialysis were excluded. Patients were grouped according to HbA 1c level and QTc time ≤ or >440 ms. Results Patients (n=214, median age 69.1 years) were grouped according to HbA 1c level (HbA 1c <7.5% [<58 mmol/mol] n=81, 7.5-8.9% [58-74 mmol/mol] n=70, >8.9% [>74 mmol/ mol] n=63). Baseline characteristics, including use of potential hypoglycaemic drugs, were similar between groups. During the 8 years of follow-up 151 patients died (70.6%) and HbA 1c < 7.5% (<58 mmol/mol) was strongly associated with increased mortality. The highest mortality was seen in patients with a combination of HbA 1c <7.5% (<58 mmol/mol) and QTc prolongation, with an 8 year mortality of 92.1% as compared with 48.8% in those with HbA 1c < 7.5% (<58 mmol/mol) but without QTc prolongation. Conclusion/interpretations HbA 1c <7.5% (<58 mmol/mol) in a high-risk population of patients with type 2 diabetes and foot ulcers is associated with a significantly higher mortality, particularly in patients with QTc prolongation.

Impact of differing glucose‐lowering regimens on the pattern of association between glucose control and survival

“…Previous studies in patients with type 2 diabetes have reported that the relationship between HbA1c, all‐cause mortality and other outcomes was not a direct association but better characterized by a J‐shaped, V‐shaped or U‐shaped association . In this study, we not only found that the pattern of association between differing levels of HbA1c and all‐cause mortality differed within specific glucose‐lowering regimens, but also that this pattern of association differed between differing glucose‐lowering regimens.…”

“…7 Thus, the optimum target for glucose control in patients with diabetes remains uncertain. This uncertainty is further complicated because both randomized trials 8,9 and observational studies 7,[10][11][12][13][14][15][16][17][18][19][20]25,26 have been unable to demonstrate a consistent pattern of association between levels of glucose control and adverse outcome, nor to explain why this may be the case.…”

Hyperbaric oxygen therapy reduces the risk of QTc interval prolongation in patients with diabetes and hard-to-heal foot ulcers

“…However, this excess risk cannot fully be explained by a higher prevalence of cardiovascular disease (CVD) or known CVD risk factors [22]. Lately, several studies have indicated the importance of long QTc time, a well-known predictor for malignant arrhythmias and death, as a predictor of all-cause mortality in patients with diabetes [4,5]. QTc prolongation is more frequently found in patients with diabetes than in non-diabetic patients [7].…”

“…This excess mortality has in part, been explained by an increased burden of traditional cardiovascular risk factors, such as hypertension, myocardial infarction, heart failure, renal dysfunction and smoking. However, these risk factors cannot fully explain this excess mortality risk, and lately studies have demonstrated an association between heart rate corrected QT interval (QTc) and all-cause and cardiovascular mortality in the general population [2,3] as well as in people with diabetes [4][5][6]. Several factors, i.e.…”

Prevalence of QT prolongation and associated LVEF changes in diabetic patients over a four-year retrospective time period

“…QT prolongation has been found in various experimental diabetes animal models, which mimic type 1 and type 2 diabetes in human beings [8,9]. While investigating the QTc interval prolongation in both type 1 and type 2 diabetes, various studies have postulated such prolongation to be associated with long-term mortality from all-causes, cardiovascular, cardiac, and ischemic heart disease [10,11]. The prevalence of QTc interval prolongation reported in diabetes are variable [12,13]; the prevalence of QTc prolongation in type 2 diabetes is 30.1% among Chinese population obtained from a outpatient retrospective study [14] and 34.6% in a hospital-based cross sectional population study from European patients [15].…”