Diabetes Metab J > Volume 41(5); 2017 > Article
Kim, Lee, and Cha: Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)
We appreciate Professor Lee's interest and agree with the comments on our article entitled “Effects of high-dose α-lipoic acid on heart rate variability of type 2 diabetes mellitus patients with cardiac autonomic neuropathy in Korea” which was published in Diabetes and Metabolism Journal [1].
Cardiac autonomic neuropathy (CAN) represents a significant cause of morbidity and mortality in diabetic patients and is associated with a high risk of cardiac arrhythmias and sudden death, which is possibly related to silent myocardial ischemia [2]. The most common symptoms of CAN are standing and include lightheadedness, weakness, palpitations, faintness, and syncope. In its early stages, CAN may be completely asymptomatic and detected only by decreased heart rate variability (HRV) with deep breathing [3]. In more advanced cases, patients may present with resting tachycardia (>100 beats/min) and exercise intolerance [4]. Advanced disease may also be associated with orthostatic hypotension (a fall in systolic or diastolic blood pressure by >20 or >10 mm Hg, respectively, upon standing without an appropriate increase in heart rate) [4]. The diagnosis includes documentation of symptoms and signs of CAN, which include impaired HRV, higher resting heart rate, and presence of orthostatic hypotension. The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive insulin therapy for type 1 diabetes mellitus reduced the incidence of CAN by 53% compared with conventional therapy [5]. The Epidemiology of Diabetes Interventions and Complications (EDIC) study, the prospective observational study of the DCCT cohort, has shown persistent beneficial effects of past glucose control on microvascular complications despite the loss of glycemic separation [6].
In type 2 diabetes mellitus, the effects of glycemic control are less conclusive. The VA Cooperative Study demonstrated no differences in the prevalence of autonomic neuropathy in type 2 diabetic mellitus patients after 2 years of tight glycemic control compared with those without tight control [7]. On the other hand, the Steno-2 Trial reported that a targeted, intensive intervention involving glucose control and multiple cardiovascular risk factors reduced the prevalence of CAN in patients with type 2 diabetes mellitus and microalbuminuria [8]. Angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers, or aldose reductase inhibitors appear to be promising but are yet to be validated [9].
We completely agree with the comments and questions. The Deutsche Kardiale Autonome-Neurophathie (DEKAN) study [10] and the Alpha Lipoic Acid in Diabetic Neuropathy (ALADIN) study [11] showed significant improvements in HRV indexes and CAN. Despite the high dosage (800 mg/day vs. 1,200 mg/day) and longer duration of treatment (4 months vs. 6 months), the results of our study did not show significant improvements in HRV indexes. However, we found a positive tendency in some of the HRV parameters of the high dosage α-lipoic acid (ALA) group. Our study described glycemic status (7.64% ALA vs. 7.65% placebo) but didn't check the status of other microvascular complications, stage of CAN, and evaluation of symptomatic improvements. We agree that further explanations and research are likely to be needed for the causes of different conclusions. We also agree that it is necessary to develop a HRV marker with a higher sensitivity such as 24 hours HRV monitoring tool. As suggested by Professor Lee, more studies are needed to clarify the efficacy and mechanisms of ALA on HRV in diabetic patients with CAN.

NOTES

CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Lee SJ, Jeong SJ, Lee YC, Lee YH, Lee JE, Kim CH, Min KW, Cha BY. Effects of high-dose α-lipoic acid on heart rate variability of type 2 diabetes mellitus patients with cardiac autonomic neuropathy in Korea. Diabetes Metab J 2017;41:275-283.
Article  PubMed  PMC 
2. Kahn JK, Sisson JC, Vinik AI. Prediction of sudden cardiac death in diabetic autonomic neuropathy. J Nucl Med 1988;29:1605-1606.
PubMed 
3. Pop-Busui R. Cardiac autonomic neuropathy in diabetes: a clinical perspective. Diabetes Care 2010;33:434-441.
Article  PubMed  PMC 
4. The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology 1996;46:1470
Article 
5. The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia 1998;41:416-423.
Article  PubMed  PMC 
6. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003;290:2159-2167.
Article  PubMed  PMC 
7. Azad N, Emanuele NV, Abraira C, Henderson WG, Colwell J, Levin SR, Nuttall FQ, Comstock JP, Sawin CT, Silbert C, Rubino FA. The effects of intensive glycemic control on neuropathy in the VA cooperative study on type II diabetes mellitus (VA CSDM). J Diabetes Complications 1999;13:307-313.
Article  PubMed 
8. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-393.
Article  PubMed 
9. Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007;115:387-397.
Article  PubMed 
10. Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care 1997;20:369-373.
Article  PubMed 
11. Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995;38:1425-1433.
Article  PubMed 


ABOUT
BROWSE ARTICLES
FOR CONTRIBUTORS
Editorial Office
101-2104, Lotte Castle President, 109 Mapo-daero, Mapo-gu, Seoul 04146, Korea​
Tel: +82-2-714-9064    Fax: +82-2-714-9084    E-mail: diabetes@kams.or.kr                

Copyright © 2022 by Korean Diabetes Association.

Developed in M2PI

Close layer