(r)Alpha Lipoic Assists With Control of Neurogenic Orthostatic Hypotension, Hypertension, and Reduces Sudden Cardiac Death in Geriatric Diabetics

Background: 10-30% of people have Orthostatic Hypotension (OH), 1/3rd of the world’s population has Hypertension (HTN), and Sudden Cardiac Death (SCD) is twice as common and the most frequent manner of death in Type 2 diabetes (DM II), all of which can involve oxidative stress. Objective: To study the effect of the potent, natural antioxidant (r)Alpha Lipoic Acid in (1) neurogenic OH (NOH), (2) HTN, and (3) DMII SCD. Key words: Oxidative stress; Alpha Lipoic acid; Orthostatic hypotension; Hypertension; Sudden death;

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The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/3276958 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Víctor Manuel Mendoza-Núñez ◽

Beatriz Isabel García-Martínez ◽

Juana Rosado-Pérez ◽

Edelmiro Santiago-Osorio ◽

José Pedraza-Chaverri ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Older Adults ◽

Lipoic Acid ◽

Glycosylated Hemoglobin ◽

Total Antioxidant Status ◽

Control Group ◽

Alpha Lipoic Acid ◽

Markers Of Inflammation

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of64±1years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline8.9±0.2vs. posttreatment8.6±0.3) and the PG (baseline8.8±0.2vs. posttreatment8.4±0.3) compared to the CG (baseline8.8±0.3vs. six months9.1±0.3) although the difference was not statistically significant (p<0.05). There was a statistically significant decrease (p<0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline100±3vs. posttreatment57±3, PG: baseline106±7vs. posttreatment77±5, and CG: baseline94±10vs. six months107±11pg/mL). Likewise, a statistically significant decrease (p<0.05) in the concentration of the RAGE was found in the EG (baseline1636±88vs. posttreatment1144±68) and the PG (baseline1506±97vs. posttreatment1016±82) compared to CG (baseline1407±112vs. six months1506±128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration numberISRCTN13159380.

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Maintenance (r) Alpha Lipoic Acid Reduces Sudden Cardiac Death in Geriatric Diabetes Mellitus II Patients

Clinical Cardiology and Cardiovascular Medicine ◽

10.33805/2639.6807.127 ◽

2020 ◽

pp. 6-11

Author(s):

Gary L Murray ◽

Joseph Colombo

Keyword(s):

Sudden Cardiac Death ◽

Autonomic Neuropathy ◽

Lipoic Acid ◽

Cardiac Death ◽

Autonomic Function ◽

Relative Risk Reduction ◽

Progressive Increase ◽

Alpha Lipoic Acid ◽

Group 2 ◽

Group 1

Background: Diabetes carries a two-fold risk of Sudden Cardiac Death (SCD). Diabetic Autonomic Neuropathy (DAN), often progressing to Cardiovascular Autonomic Neuropathy (CAN, critically low parasympathetic tone [P]), increases death 3.5-fold over 5 years, half sudden or non-renal. Oxidative stress is a major cause of DAN. Also, increased sympathetic tone (S), High Sympathovagal Balance [SB>2.5] increases SCD risk. Objective: Dysautonomic diabetic II patients were treated with the antioxidant (r) Alpha Lipoic Acid (ALA), autonomic function followed, and Sudden Death (SD) compared to untreated patients. Methods: 133 patients (mean age 66y/o) with DAN or CAN, diagnosed using the ANX 3.0 Autonomic Monitor (Physio PS, Inc., Atlanta, GA) was offered (r)-ALA: 83 agreed (Group 1), and 50 refused (Group 2). P and S were re-measured up to 3 times/yr (mean f/u 6.31 yrs); SCDs were recorded. Results: A 43% Relative Risk Reduction (RRR) in SCD occurred with (r)-ALA (25% SCD Group 1 vs. 44% SCD Group 2, p=0.0076). Initial to final patients with high SB or CAN were 21.7%-12% (p=0.010), 10.8%-15.7% (p=0.045), Group 1 vs. 24%-22% (p=ns), 6%-12% (p=0.083), Group 2. Only Group 1 survivors increased mean resting P. The progressive increase in P’s decline, increasing CAN risk, in the other patients correlated with mortality (p<0.001) and (r) ALA dose. Initially, Group 1 had insignificantly less high SB (p=0.449) and significantly more CAN (p=0.013) vs. Group 2. Finally, Group 1 had significantly less high SB (p=0.0967) vs. Group 2, also improving to insignificantly more CAN (p=0.261). Conclusion: (r)-ALA was associated with a 43% RRR of SCD and favorable P and S changes.

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The alpha-lipoic acid decreases urinary podocalyxin excretion in type 2 diabetics by inhibiting oxidative stress in vivo

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2014.09.011 ◽

2015 ◽

Vol 29 (1) ◽

pp. 64-67 ◽

Cited By ~ 6

Author(s):

Haiyan Lin ◽

Shandong Ye ◽

Jiang Xu ◽

Wei Wang

Keyword(s):

Oxidative Stress ◽

Lipoic Acid ◽

Alpha Lipoic Acid ◽

Type 2 Diabetics

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A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

International Journal of Arrhythmia ◽

10.1186/s42444-020-00029-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Hyun Sok Yoo ◽

Nancy Medina ◽

María Alejandra von Wulffen ◽

Natalia Ciampi ◽

Analia Paolucci ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Long Qt Syndrome ◽

Cardiac Death ◽

Frameshift Mutation ◽

Alpha Subunit ◽

Syndrome Type ◽

Long Qt ◽

Qt Syndrome ◽

Congenital Long Qt Syndrome

Abstract Background The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. The carriers of the pathogenic variant of KCNH2 gene manifest a phenotype characterized by prolongation of QT interval and increased risk of sudden cardiac death due to life-threatening ventricular tachyarrhythmias. Results A family composed of 17 members with a family history of sudden death and recurrent syncopes was studied. The DNA of proband with clinical manifestations of long QT syndrome was analyzed using a massive DNA sequencer that included the following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 and TRDN. DNA sequencing of proband identified a novel pathogenic variant of KCNH2 gene produced by a heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting in the synthesis of a truncated alpha subunit of the Kv11.1 ion channel. Eight family members manifested the phenotype of long QT syndrome. The study of family segregation using Sanger sequencing revealed the identical variant in several members of the family with a positive phenotype. Conclusions The clinical and genetic findings of this family demonstrate that the novel frameshift mutation causing haploinsufficiency can result in a congenital long QT syndrome with a severe phenotypic manifestation and an elevated risk of sudden cardiac death.

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