Effect of Controlling Hyperglycemia With Diet on QT Abnormalities in Newly Diagnosed Patients With Type 2 Diabetes

Abstract

Several clinical trials (1) have demonstrated that vitamin E does not reduce future major cardiovascular (CV) events. However, these trials could not rule out the potential benefit for highrisk subgroups. Diabetic individuals who are homozygous for the haptoglobin 2 allele (Hp 2-2) are at high risk for CV events (2-4); moreover, the Hp 2-2 protein product is an inferior antioxidant compared with the Hp 1 allele (5). We therefore hypothesized that vitamin E may reduce CV events in Hp 2-2 diabetic individuals.Hp type was measured in 3,167 participants (1,078 with diabetes) of the Heart Outcomes Prevention Evaluation (HOPE) trial, which evaluated the 4.5-year effects of 400 IU vitamin E daily on the primary composite of CV death, myocardial infarction, and stroke (1). No significant benefit of vitamin E supplementation was detected in either the entire group or in the diabetic subset, consistent with what was previously reported for the entire HOPE cohort (1). In Hp 2-2 diabetic participants, there was a trend toward a reduced primary composite outcome (relative risk 0.70 [95% CI 0.45-1.10]) and a statistically significant reduction in the risk of CV death (0.45 [0.23-0.90]) and nonfatal myocardial infarction (0.57 [0.33-0.97]). However, this trend was not observed for strokes (1.15 [0.47-2.82]), and there was no statistical interaction between vitamin E use and haptoglobin type for either the composite outcome or any of its components.In conclusion, the absence of any statistical interaction indicates that these data do not support the hypothesis that the effects of vitamin E differed by Hp phenotype. Therefore, the results noted above in Hp 2-2 diabetic individuals demonstrating a significant reduction in CV death and myocardial infarction could be spurious and clearly require prospective testing in future trials. Acknowledgments -This study was funded by the Kennedy-Leigh Trust and the Israel Science Foundation. ANDREW P. LEVY, MD• Recently, several studies have reported a high prevalence of QT prolongation and increased QT dispersion (QTd) in patients with diabetes. These abnormalities have been shown to be associated with sudden death and poor survival in both type 1 (1) and type 2 (2) diabetes. QTd, i.e., the difference between the maximum and minimum QT intervals on the 12-lead electrocardiogram (ECG) (QTd ϭ QT max Ϫ QT min), is claimed to reflect the degree of inhomogeneity of myocardial repolarization. The role of hyperglycemia in causing QT abnormalities in people with diabetes is not clear. The present study was therefore undertaken to assess the effect of controlling hyperglycemia on QT intervals and dispersion.A total of 26 newly diagnosed type 2 diabetic patients with no coronary artery disease or autonomic dysfunction were recruited. Each was examined and had three ECGs recorded before and after 8 weeks of dietary intervention. All ECGs were analyzed automatically by the previously validated Glasgow program (3). The Hodges formula [corrected QT (QTc) ϭ QT ϩ 1.75 (rate Ϫ 60)] was used to correct QT i...

Modelling the relationship between continuously measured glucose and electrocardiographic data in adults with type 1 diabetes mellitus

“…Black bars show where there was a significant relationship hypoglycaemia has often been implicated especially in the presence of cardiovascular disease. 21,22,[33][34][35] The statistical modelling presented here allows for a changing relationship between QTc and glucose, and we have found times when there were associations and others were there were none.…”

“…Furthermore, to minimize clinical heterogeneity, we only included T1DM male participants with no previous cardiovascular events, though studies have shown that in the presence of neuropathy, the absolute cardiovascular disease risk in men and women was equal 32 . Previous studies showed that QTc prolongation is prevalent in people with T2DM, ranging from 15.4% to 67%, and hypoglycaemia has often been implicated especially in the presence of cardiovascular disease 21,22,33–35 …”

Electrical Features of the Diabetic Myocardium. Arrhythmic and Cardiovascular Safety Considerations in Diabetes

“…It is difficult to estimate the prevalence of longer QTc among diabetics. The different characteristics of the cohorts in each study and the formula used to adjust the QT for heart rate (Bazett, Fridericia, Hodges, others) lead to heterogeneous results, with prevalence estimates ranging from 30 to 66% ( Veglio et al, 2002 ; Kumar et al, 2004 ; Li et al, 2012b ; Cox et al, 2014 ; Lu et al, 2017 ). In these studies, recruited participants usually exhibited diabetes with several years of duration and therefore received antidiabetic medication.…”

Dysglycemia and arrhythmias

“…Besides, hyperglycemia has also been associated with increased QTc dispersion (QTd) among healthy individuals, which reflects the inhomogeneity of myocardial repolarization[ 58 ]. However, a prospective study ( n = 26) failed to observe a significant change in QTc or QTd among patients with newly diagnosed T2DM[ 60 ], which may be due to the small sample size, short follow-up duration and unknown confounding factors.…”