Long-term effect of epalrestat on cardiac autonomic neuropathy in subjects with non-insulin dependent diabetes mellitus

Ikeda, Tadasu; Iwata, Koichi; Tanaka, Yasushi

doi:10.1016/s0168-8227(99)00015-7

Cited by 36 publications

(21 citation statements)

References 14 publications

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“…108 The use of aldose reductase inhibitors such as sorbinil improved resting and maximum cardiac output, and epalrestat improved MIBG uptake and HRV in patients with mild abnormalities but not in those with advanced CAN. 109 The most salutary lesson, however, derives from the Steno memorial study by Gaede et al, 110 in which intensive multifactorial management aimed at control of BP, lipids, HBA1c, use of aspirin, vitamins E and C, and ACE inhibitors reduced CAN by 68%. Thus, it is important to diagnose CAN because the outlook is not as dismal as was once perceived; there are now symptomatic therapies that can reorient the functional abnormalities toward improved function, as well as therapies that provide prospects for reversal.…”

Section: Potential For Reversal Of Canmentioning

confidence: 99%

Diabetic Cardiovascular Autonomic Neuropathy

2007

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Section: Potential For Reversal Of Canmentioning

confidence: 99%

Diabetic Cardiovascular Autonomic Neuropathy

2007

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“…Although several published reports have described the efficacy and safety of epalrestat (13)(14)(15)(16)(17), including a doubleblind, placebo-controlled study (13), no long-term or large population studies have been conducted. Therefore, the Aldose Reductase Inhibitor-Diabetes Complications Trial (ADCT) was initiated to evaluate the efficacy and safety of longterm administration of epalrestat in subjects with mild diabetic neuropathy.…”

mentioning

confidence: 99%

Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy

Hotta

Akanuma²,

Kawamori³

et al. 2006

Diabetes Care

323

164

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RESEARCH DESIGN AND METHODS -Subjects with diabetic neuropathy, median motor nerve conduction velocity (MNCV) Ն40 m/s, and HbA 1c Յ9% were enrolled in this open-label, multicenter study and randomized to 150 mg/day epalrestat or a control group. After excluding the withdrawals, 289 (epalrestat group) and 305 (control group) patients were included in the analyses. The primary end point was change from baseline in median MNCV at 3 years. Secondary end points included assessment of other somatic nerve function parameters (minimum F-wave latency [MFWL] of the median motor nerve and vibration perception threshold [VPT]), cardiovascular autonomic nerve function, and subjective symptoms.RESULTS -Over the 3-year period, epalrestat prevented the deterioration of median MNCV, MFWL, and VPT seen in the control group. The between-group difference in change from baseline in median MNCV was 1.6 m/s (P Ͻ 0.001). Although a benefit with epalrestat was observed in cardiovascular autonomic nerve function variables, this did not reach statistical significance compared with the control group. Numbness of limbs, sensory abnormality, and cramping improved significantly with epalrestat versus the control group. The effects of epalrestat on median MNCV were most evident in subjects with better glycemic control and with no or mild microangiopathies.CONCLUSIONS -Long-term treatment with epalrestat is well tolerated and can effectively delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease, particularly in subjects with good glycemic control and limited microangiopathy.

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“…Aldose reductase inhibitor (ARI) drugs block the entry of glucose into the sorbitol pathway and have been developed for the treatment of diabetic peripheral (18,19) and autonomic neuropathy (20,21). They appear to increase cardiac output during exercise in patients with type 2 diabetes (22).…”

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Cardiac Abnormalities in Diabetic Patients With Neuropathy

et al. 2004

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OBJECTIVE -The goal of this study was to determine whether treatment with an aldose reductase inhibitor (ARI) has beneficial effects on asymptomatic cardiac abnormalities in diabetic patients with neuropathy.RESEARCH DESIGN AND METHODS -Diabetic subjects with neuropathy (n ϭ 81) with either a low diastolic peak filling rate or impaired augmentation of left ventricular (LV) ejection fraction (LVEF) during maximal bicycle exercise were identified by gated radionuclide ventriculography. Coronary artery disease, left ventricular hypertrophy, and valvular heart disease were excluded by clinical evaluation, myocardial perfusion imaging, and echocardiography. Subjects were randomized to receive blinded treatment with either the placebo or the ARI zopolrestat 500 or 1,000 mg daily for 1 year. RESULTS-After 1 year of ARI treatment, there were increases in resting LVEF (P Ͻ 0.02), cardiac output (P Ͻ 0.03), LV stroke volume (P Ͻ 0.004), and exercise LVEF (P Ͻ 0.001). In placebo-treated subjects, there were decreases in exercise cardiac output (P Ͻ 0.03), stroke volume (P Ͻ 0.02), and end diastolic volume (P Ͻ 0.04). Exercise LVEF increased with ARI treatment independent of blood pressure, insulin use, or the presence of baseline abnormal heart rate variability. There was no change in resting diastolic filling rates in either group.CONCLUSIONS -Diabetic patients with neuropathy have LV abnormalities that can be stabilized and partially reversed by ARI treatment.

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Long-term effect of epalrestat on cardiac autonomic neuropathy in subjects with non-insulin dependent diabetes mellitus

Cited by 36 publications

References 14 publications

Diabetic Cardiovascular Autonomic Neuropathy

Diabetic Cardiovascular Autonomic Neuropathy

Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy

Cardiac Abnormalities in Diabetic Patients With Neuropathy

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