QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Stettler, Christoph; Bearth, A.; Allemann, Sabin; Zwahlen, Marcel; Zanchin, L; Deplazes, M.; Christ, Emanuel; Teuscher, A; Diem, Peter

doi:10.1007/s00125-006-0483-1

Cited by 90 publications

(52 citation statements)

References 48 publications

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“…Disrupted I CaL inactivation may cause a long QTc interval, a precursor for sudden cardiac arrest that occurred in patients with type 1 and type 2 diabetes (14,21), under obese conditions. Prolongation of QTc interval has also been demonstrated as an independent risk factor in type 1 and type 2 diabetes (34,37,38), as well as a significant predictor of cardiac death (31,34). Our work has provided one ionic mechanism: defective I CaL inactivation contributed to the prolonged QTc interval in the OZR heart.…”

Section: Discussionmentioning

confidence: 83%

Defective calcium inactivation causes long QT in obese insulin-resistant rat

Lin

Huang

Kan

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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majority of diabetic patients who are overweight or obese die of heart disease. We suspect that the obesity-induced insulin resistance may lead to abnormal cardiac electrophysiology. We tested this hypothesis by studying an obese insulin-resistant rat model, the obese Zucker rat (OZR). Compared with the age-matched control, lean Zucker rat (LZR), OZR of 16 -17 wk old exhibited an increase in QTc interval, action potential duration, and cell capacitance. Furthermore, the L-type calcium current (I CaL) in OZR exhibited defective inactivation and lost the complete inactivation back to the closed state, leading to increased Ca 2ϩ influx. The current density of I CaL was reduced in OZR, whereas the threshold activation and the current-voltage relationship of I CaL were not significantly altered. L-type Ba 2ϩ current (IBaL) in OZR also exhibited defective inactivation, and steady-state inactivation was not significantly altered. However, the current-voltage relationship and activation threshold of I BaL in OZR exhibited a depolarized shift compared with LZR. The total and membrane protein expression levels of Cav1.2 [pore-forming subunit of L-type calcium channels (LTCC)], but not the insulin receptors, were decreased in OZR. The insulin receptor was found to be associated with the Cav1.2, which was weakened in OZR. The total protein expression of calmodulin was reduced, but that of Cav␤2 subunit was not altered in OZR. Together, these results suggested that the 16-to 17-wk-old OZR has 1) developed cardiac hypertrophy, 2) exhibited altered electrophysiology manifested by the prolonged QTc interval, 3) increased duration of action potential in isolated ventricular myocytes, 4) defective inactivation of ICaL and IBaL, 5) weakened the association of LTCC with the insulin receptor, and 6) decreased protein expression of Cav1.2 and calmodulin. These results also provided mechanistic insights into a remodeled cardiac electrophysiology under the condition of insulin resistance, enhancing our understanding of long QT associated with obese type 2 diabetic patients. obesity; insulin resistance; long QT; action potential; L-type calcium current; calmodulin OBESITY IS DIRECTLY LINKED to type 2 diabetes, which has become an increasingly public health problem. In 2004, heart disease was noted on 65-68% of diabetes-related death among people aged 65 years and older

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Section: Discussionmentioning

confidence: 83%

Defective calcium inactivation causes long QT in obese insulin-resistant rat

Lin

Huang

Kan

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…The main finding of 23-year follow-up study (23) was that in subjects with type 1 diabetes QTc, but not resting HR was associated with an increased risk of all-cause mortality and mortality due to cardiovascular and cardiac disease.…”

Section: Discussionmentioning

confidence: 96%

Natural progression of cardiac autonomic neuropathy in patients with type 1 diabetes: a four-year follow-up study

Dayem¹,

Battah²,

Soliman³

2011

Anadolu Kardiyol Derg

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ÖZETAmaç: Kardiyak otonom nöropatinin doğal seyrine daha fazla ışık tutmak için 4 yıl boyunca takip edilen Tip 1 diyabet hastalarında kardiyak otonom nöropati sıklığı ve klinik özelliklerini belirlemek. Yöntemler: Ewing ve Clarke (1985) tarafından önerilen standart testler kullanılarak, ilk olarak çalışılan 57 hastadan oluşan kohort gözlemsel ileriye dönük bir çalışmadır. İki yıllık takipte, 46 hasta yeniden değerlendirildi. Sonraki diğer bir 2 yılda üçüncü kez aynı protokol kullanılarak: Asıl çalışma-dan 55 hasta tekrar değerlendirildi. Kontrol grubu, aynı yaş ve cinsiyette 30 sağlıklı gönüllüden oluşmaktadır. İstatistiksel analizler McNemar testi, tekrarlanan ölçümler için ANOVA, eşleştirilmiş ve eşleştirilmemiş t-testleri ile yapılmıştır. Bulgular: Başlangıçta, kardiyak otonom noröpati (KON) saptanma sıklığı %14'tür. İkinci muayenede Q-Tc aralığı, anormal kardiyovasküler refleksi (CVRs) olan hastalarda anlamlı şekilde daha yüksek bulunmuştur (0.4±0.04 karşın 0.5±0.05 sn, p=0.006). Birinci ve üçüncü muayene arasında on sekiz hasta CVRs testinde bozulma gösterdi. Glikozile hemoglobin rehberliğinde, (8.5±1.4 karşın 9.9±1.5%, p=0.05) glisemik kontrollerinde ve albümin kreatinin oranında (4.4±4.0 karşın 28.2±28.0 mg/g kreatinin , p=0.04) bozulma vardır. Diğer yandan, 12 hasta CVRs testinde gerileme gösterdi. Sadece insülin dozunda anlamlı şekilde azalma oldu (1.8±1.3 karşın 1.1±0.3 doz/kg, p=0.02). Sonuç: Çalışmanın başlangıcında, diyabetik hastalarda saptanan KON sıklığı yüksektir. Kardiyak otonom nöropatilerinde bozulma olan diyabet hastalarında, glikozile hemoglobin, sistolik ve diyastolik kan basıncı anlamlı olarak yükseldi. Ancak, kardiyak otonom nöropatilerinde gerileme olan diyabet hastalarında insülin dozu anlamlı olarak azaldı. (Anadolu Kardiyol Derg 2011; 11: 224-31) Anahtar kelimeler: Kardiyak otonom nöropati, tip 1 diyabet, komplikasyon, doğal seyir ABSTRACT Objective: To determine the prevalence and clinical characteristics of cardiac autonomic neuropathy in type 1 diabetic patients who were followed up for 4 years to shed further light on the natural progression of cardiac autonomic neuropathy. Methods: It is a prospective cohort observational study, consisted of 57 patients who were originally studied using the standard tests proposed by Ewing and Clarke (1985). At two years follow up, 46 patients were reevaluated, 55 patients from the original study were reevaluated after another 2 years for the 3 rd time using the same protocol. The control group comprised 30 age and sex matched healthy volunteers. McNemar test, ANOVA for repeated measurements, paired t test and unpaired t test were used for statistical analyses. Results: The prevalence of established cardiac autonomic neuropathy (CAN) at the beginning was 14%. Q-Tc intervals were found to be significantly higher in patients with abnormal cardiovascular reflex (CVRs) in the 2nd examination (0.4±0.04 vs 0.5±0.05 sec, p=0.006). Eighteen patients showed deterioration of their CVRs test between 1st and 3rd examination. There was deterioration of their...

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“…Similar to impaired autonomic function as measured by Ewing's tests, HRV and BRS, prolonged QTc duration is a predictor of cardiovascular mortality in type 1 and type 2 diabetes mellitus [41,117,118]. Prolonged QTc is associated with traditional risk factors in type 1 diabetic patients, underscoring the relation between (subclinical) cardiovascular damage and autonomic dysfunction [119].…”

Section: Diabetes Mellitusmentioning

confidence: 96%

Autonomic Dysfunction in Diabetes: a Consequence of Cardiovascular Damage

Lefrandt¹,

Smit²,

Zeebregts³

et al. 2010

CDR

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In 1976, D.J. Ewing showed a clear survival disadvantage for diabetic patients that had 'diabetic autonomic neuropathy', as assessed by heart rate and blood pressure variations during a battery of bedside tests. However, these variations do not solely depend on autonomic nervous system function, but also and possibly to a more important extent on the integrity of cardiovascular autonomic reflex loops. Increased intima media thickness at the site of the baroreceptors, reduced vascular distensibility, endothelial dysfunction and impaired cardiac function contribute to the cardiovascular autonomic dysfunction. Interestingly, these abnormalities are closely associated with the presence of (micro-) albuminuria that is regarded as a reflection of endothelial dysfunction or vascular damage in diabetes mellitus. Modern techniques to assess cardiovascular autonomic, vascular and cardiac function have improved the ability to detect early abnormalities. Analysis of heart rate variability, baroreflex sensitivity, muscle sympathetic nervous activity, LNMAinfusions and advanced echocardiography have shown that it is the interplay between autonomic control and cardiac and vascular properties that determines cardiovascular autonomic function. Moreover, these modern techniques have improved power to predict survival in diabetic patients in comparison with the classical Ewing's bedside tests. In conclusion, cardiovascular damage may be more important in cardiovascular autonomic dysfunction than neural function.

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QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Cited by 90 publications

References 48 publications

Defective calcium inactivation causes long QT in obese insulin-resistant rat

Defective calcium inactivation causes long QT in obese insulin-resistant rat

Natural progression of cardiac autonomic neuropathy in patients with type 1 diabetes: a four-year follow-up study

Autonomic Dysfunction in Diabetes: a Consequence of Cardiovascular Damage

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