Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Diabetes & Metabolic Disorders
Published in: Journal of Diabetes & Metabolic Disorders 2/2018

01-12-2018 | Research Article

Effect of glycemic control and disease duration on cardiac autonomic function and oxidative stress in type 2 diabetes mellitus

Authors: Shalini Verma, Rizwan Alam, Irshad Ahmad, Deepika Singla, Kamran Ali, Mohammed E. Hussain

Published in: Journal of Diabetes & Metabolic Disorders | Issue 2/2018

Login to get access

Abstract

Purpose

Cardiac autonomic neuropathy (CAN) is a commonly overlooked complication of type 2 diabetes mellitus (T2DM), with a complex pathogenesis involving hyperglycemia-induced oxidative stress which results in neuronal ischemia and cellular death. The level of hyperglycemia as well as disease duration might be significant determinants of the prognosis of T2DM, but limited studies have explored their relationship with these diabetic complications. Therefore, the purpose of this study was to examine the effect of glycemic control and disease duration on cardiac autonomic function and oxidative stress in patients with T2DM.

Methods

60 T2DM patients along with 63 healthy controls were recruited for the study. Diabetic patients were further classified based on glycemic control (HbA1c levels <8% vs. ≥8%) and disease duration (<5 vs. 5–10 vs. >10 years). All participants were assessed for cardiac autonomic function (HRR: heart rate recovery; HRV: heart rate variability), levels of antioxidant enzymes (CAT: catalase; SOD: superoxide dismutase), serum nitric oxide (NO) and other cardiometabolic risk factors (resting blood pressure, glycemic and lipid profile).

Results

T2DM patients showed a significant reduction in HRR, HRV, CAT, SOD and an increase in LFnu, LF: HF ratio and NO. These impairments were significantly greater for the group with poor glycemic control (p < 0.05). However, no difference for these parameters was observed with respect to different disease durations.

Conclusion

Cardiac autonomic regulation and endogenous antioxidant defense were compromised and levels of nitric oxide found to be raised in patients with Type 2 diabetes. These findings were more pronounced in subjects with poor glycemic control.
Literature
1.
International Diabetes Federation. IDF Diabetes Atlas, 8th edn. Brussels, Belgium:International Diabetes Federation, 2017.
2.
González EM, Johansson S, Wallander MA, Rodríguez LG. Trends in the prevalence and incidence of diabetes in the UK: 1996–2005. J Epidemiol Community Health. 2009 Apr 1;63(4):332–6.CrossRefPubMed
3.
American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012 Jan 1;35(Supplement 1):S11–63.CrossRef
4.
5.
Hazari MA, Khan RT, Reddy BR, Hassan MA. Cardiovascular autonomic dysfunction in type 2 diabetes mellitus and essential hypertension in a south Indian population. Neurosciences (Riyadh). 2012 Apr 1;17(2):173–5.
6.
Pappachan JM, Sebastian J, Bino BC, Jayaprakash K, Vijayakumar K, Sujathan P, et al. Cardiac autonomic neuropathy in diabetes mellitus: prevalence, risk factors and utility of corrected QT interval in the ECG for its diagnosis. Postgrad Med J. 2008 Apr 1;84(990):205–10.CrossRefPubMed
7.
Verma S, Bhati P, Ahmad I, Masroor S, Ali K, Singla D, et al. Co-existence of hypertension worsens post-exercise cardiac autonomic recovery in type 2 diabetes. Indian Heart J. 2018 Jul;18
8.
Wada R, Yagihashi S. Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci. 2005 Jun;1043(1):598–604.CrossRefPubMed
9.
Griesmacher A, Kindhauser M, Andert SE, Schreiner W, Toma C, Knoebl P, et al. Enhanced serum levels of thiobarbituric-acid-reactive substances in diabetes mellitus. Am J Med. 1995 May 1;98(5):469–75.CrossRefPubMed
10.
Palanduz S, Ademoğlu E, Gökkuşu C, Tamer S. Plasma antioxidants and type 2 diabetes mellitus. Res Commun Mol Pathol Pharmacol. 2001;109(5–6):309–18.PubMed
11.
ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560–72.CrossRef
12.
Kalyani RR, Saudek CD, Brancati FL, Selvin E. Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and nutrition examination survey (NHANES), 1999-2006. Diabetes Care. 2010;33:1055–60.CrossRefPubMedPubMedCentral
13.
Stolar M. Glycemic control and complications in type 2 diabetes mellitus. Am J Med. 2010 Mar 31;123(3):S3–11.CrossRefPubMed
14.
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129–39.CrossRefPubMed
15.
Ismail-Beigi F. Craven T, Banerji MA, Basile J, Calles J, Cohen RM, Cuddihy R, Cushman WC, Genuth S, Grimm RH Jr, Hamilton BP, Hoogwerf B, Karl D, Katz L, Krikorian a, O’Connor P, pop-Busui R, Schubart U, Simmons D, Taylor H, Thomas a, Weiss D, Hramiak I; ACCORD trial group. Effect of intensive treatment of hyperglycaemiaon microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376:419–30.CrossRefPubMedPubMedCentral
16.
Jelinek HF, Osman WM, Khandoker AH, Khalaf K, Lee S, Almahmeed W, et al. Clinical profiles, comorbidities and complications of type 2 diabetes mellitus in patients from United Arab Emirates. BMJ Open Diabetes Research and Care. 2017 Aug;5(1):e000427.CrossRefPubMed
17.
Misra A, Khurana L. Obesity-related non-communicable diseases: south Asians vs white Caucasians. Int J Obes. 2011 Feb;35(2):167–87.CrossRef
18.
Verma S, Moiz JA, Anwer S, Alghadir AH, Hussain ME. A dose-response study of aerobic training for oxygen uptake, oxidative stress and cardiac autonomic function in type 2 diabetes mellitus: study protocol for a randomized controlled trial. Trials. 2018 Dec;19(1):289.CrossRefPubMedPubMedCentral
19.
Sacre JW, Jellis CL, Coombes JS, Marwick TH. Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy. Diabet Med. 2012 Sep 1;29(9):e312–20.CrossRefPubMed
20.
Buse JB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus. Circulation. 2007 Jan 2;115(1):114–26.CrossRefPubMed
21.
Pagani M, Malfatto G, Pierini S, Casati R, Masu AM, Poli M, et al. Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy. J Auton Nerv Syst. 1988 Aug 1;23(2):143–53.CrossRefPubMed
22.
Bernardi L, Ricordi L, Lazzari P, Solda P, Calciati A, Ferrari MR, et al. Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease. Circulation. 1992 Nov 1;86(5):1443–52.CrossRefPubMed
23.
Liao D, Cai J, Brancati FL, Folsom A, Barnes RW, Tyroler HA, et al. Association of vagal tone with serum insulin, glucose, and diabetes mellitus—the ARIC study. Diabetes Res Clin Pract. 1995 Dec 1;30(3):211–21.CrossRefPubMed
24.
Singh JP, Larson MG, O’Donnell CJ, Wilson PF, Tsuji H, Lloyd-Jones DM, et al. Association of hyperglycemia with reduced heart rate variability (the Framingham heart study). Am J Cardiol. 2000 Aug 31;86(3):309–12.CrossRefPubMed
25.
Santini V, Ciampittiello G, Gigli F, Bracaglia D, Baroni A, Cicconetti E, et al. QTc and autonomic neuropathy in diabetes: effects of acute hyperglycaemia and n-3 PUFA. Nutr Metab Cardiovasc Dis. 2007 Dec 31;17(10):712–8.CrossRefPubMed
26.
Rothberg LJ, Lees T, Clifton-Bligh R, Lal S. Association between heart rate variability measures and blood glucose levels: implications for noninvasive glucose monitoring for diabetes. Diabetes Technol Ther. 2016 Jun 1;18(6):366–76.CrossRefPubMed
27.
Tarvainen MP, Cornforth DJ, Kuoppa P, Lipponen JA, Jelinek HF. Complexity of heart rate variability in type 2 diabetes-effect of hyperglycemia. InEngineering in Medicine and Biology Society (EMBC), 2013 35th Annual International Conference of the IEEE 2013 Jul 3 (pp. 5558–5561). IEEE.
28.
Godin DV, Wohaieb SA, Garnett ME, Goumeniouk AD. Antioxidant enzyme alterations in experimental and clinical diabetes. Mol Cell Biochem. 1988 Dec 1;84(2):223–31.CrossRefPubMed
29.
Paolisso G, Giugliano D. Oxidative stress and insulin action: is there a relationship? Diabetologia. 1996 Mar 1;39(3):357–63.CrossRefPubMed
30.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.CrossRefPubMed
31.
Mercuri F, Quagliaro L, Ceriello A. Oxidative stress in diabetes. Diabetes Technol Ther. 2000;2(4):589–600.CrossRefPubMed
32.
Likidlilid A, Patchanans N, Peerapatdit T. Lipid peroxidation and antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. J Med Assoc Thail. 2010;93:682–93.
33.
Al-Rawi NH. Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics. Diab Vasc Dis Res. 2011;8:22–8.CrossRefPubMed
34.
Dincer Y, Akcay T, Alademir Z, Ilkova H. Effect of oxidative stress on glutathione pathway in RBCs from patients with IDDM. Metabolism. 2002;51:1360–2.CrossRefPubMed
35.
Ceriello A, dello Russo P, Amstad P, Cerutti P. High glucose induces antioxidant enzymes in human endothelial cells in culture: evidence linking hyperglycemia and oxidative stress. Diabetes. 1996 Apr 1;45(4):471–7.CrossRefPubMed
36.
Sechi LA, Ceriello A, Griffin CA, Catena C, Amstad P, Schambelan M, et al. Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus. Diabetologia. 1997 Jan;40(1):23–9.CrossRefPubMed
37.
Lodovici M, Bigagli E, Bardini G, Rotella CM. Lipoperoxidation and antioxidant capacity in patients with poorly controlled type 2 diabetes. Toxicol Ind Health. 2009;25:337–41.CrossRefPubMed
38.
Bigagli E, Raimondi L, Mannucci E, Colombi C, Bardini G, Rotella CM, et al. Lipid and protein oxidation products, antioxidant status and vascular complications in poorly controlled type 2 diabetes. The British Journal of Diabetes & Vascular Disease. 2012;12:33–9.CrossRef
39.
Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, et al. Antioxidant enzymes and lipid peroxidation in type 2 diabetes mellitus patients with and without nephropathy. N Am J Med Sci. 2013 Mar;5(3):213–9.CrossRefPubMedPubMedCentral
40.
Madi M, Babu S, Kumari S, Shetty S, Achalli S, Madiyal A, et al. Status of serum and salivary levels of superoxide dismutase in type 2 diabetes mellitus with oral manifestations: a case control study. Ethiopian journal of health sciences. 2016;26(6):523–32.CrossRefPubMedPubMedCentral
41.
Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, et al. Hyperglycaemia enhances nitric oxide production in diabetes: a study from south Indian patients. PLoS One. 2015 Apr 20;10(4):e0125270.CrossRefPubMedPubMedCentral
42.
Aydın A, Orhan H, Sayal A, Özata M, Şahin G, Işımer A. Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control. Clin Biochem. 2001 Feb;34(1):65–70.CrossRefPubMed
43.
Izumi N, Nagaoka T, Mori F, Sato E, Takahashi A, Yoshida A. Relation between plasma nitric oxide levels and diabetic retinopathy. Jpn J Ophthalmol. 2006;50:465–8.CrossRefPubMed
44.
Ozcelik O, Algul S. Nitric oxide levels in response to the patients with different stage of diabetes. Cell Mol Biol (Noisy le Grand). 2017;63(1):49–52.CrossRef
45.
Ghosh A, Sherpa ML, YazumBhutia RP, Dahal S. Serum nitric oxide status in patients with type 2 diabetes mellitus in Sikkim. International Journal of Applied and Basic Medical Research. 2011 Jan;1(1):31–5.CrossRefPubMedPubMedCentral
46.
Tessari P, Cecchet D, Cosma A, Vettore M, Coracina A, Millioni R, Iori E, Puricelli L, Avogaro A, Vedovato M (2010) Nitric oxide synthesis is reduced in subjects with type 2 diabetes and nephropathy. Diabetes 59:2152–2159. pmid:20484137.
47.
Wu G. Nitric oxide synthesis and the effect of aminoguanidine and NG-monomethyl-L-arginine on the onset of diabetes in the spontaneously diabetic BB rat. Diabetes 1995 Mar 1;44(3):360–4.a, 364.
48.
Fujimoto M, Shimizu N, Kunii K, Martyn JAJ, Ueki K, Kaneki M (2005) A role for iNOS in fasting hyperglycemia and impaired insulin signalling in the liver of obese diabetic mice. Diabetes 54(5): 1340–1348. pmid:15855318.
49.
Pietroa ND, Tomoa PD, Silvestrea SD, Giardinelli A, Pipino C, et al. (2013) Increased iNOS activity in vascular smooth muscle cells from diabetic rats: potential role of Ca2þ/calmodulin-dependent protein kinase II delta 2 (CaMKIId2). Atherosclerosis 226:88–94. pmid:23177014.
50.
Guzik TJ, West NE, Pillai R, Taggart DP, Channon KM. Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension. 2002 Jun 1;39(6):1088–94.CrossRefPubMed
51.
Nosarev AV, Smagliy LV, Anfinogenova Y, Popov SV, Kapilevich LV. Exercise and NO production: relevance and implications in the cardiopulmonary system. Frontiers in cell and developmental biology. 2015 Jan 7;2:73.CrossRefPubMedPubMedCentral
Metadata
Title
Effect of glycemic control and disease duration on cardiac autonomic function and oxidative stress in type 2 diabetes mellitus
Authors
Shalini Verma
Rizwan Alam
Irshad Ahmad
Deepika Singla
Kamran Ali
Mohammed E. Hussain
Publication date
01-12-2018
Publisher
Springer International Publishing
Published in
Journal of Diabetes & Metabolic Disorders / Issue 2/2018
Electronic ISSN: 2251-6581
DOI
https://doi.org/10.1007/s40200-018-0354-6

Other articles of this Issue 2/2018

Journal of Diabetes & Metabolic Disorders 2/2018 Go to the issue

Research Article

The potential of N-glycosylation profiles as biomarkers for monitoring the progression of Type II diabetes mellitus towards diabetic kidney disease

Research Article

Characteristics of hyperglycemic crises in an adult population in a teaching hospital in Colombia

Research Article

The interaction of dyslipidaemia with glycaemia in an adult population study

Research Article

Adherence to medications, self-care activity, and HbA1c status among patients with type 2 diabetes living in an urban area of Iran

Review Article

Menopause and metabolic syndrome in the Middle East countries; a systematic review and meta-analysis study

Research Article

The effect of dietary fat on behavior in mice

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits