Advertisement

Glycemic profile variability: An independent risk factor for diabetic neuropathy in patients with type 2 diabetes

Published:December 01, 2022DOI:https://doi.org/10.1016/j.pcd.2022.11.011

      Highlights

      • FBS, 2hPP, HbA1c variability are significantly higher in DPN-developed diabetic patients.
      • CV- FBS, CV-FBS 10 % and 20 %, CV-2hpp 20 % and 5 %, and CV-HbA1c 10 % as potential risk factors for DPN development.
      • Patients who developed DPN had significantly higher variabilities of FBS.

      Abstract

      Background

      Impaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM.

      Methods

      Since February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test.

      Results

      Individuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM.

      Conclusion

      Variability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Lai Y.-R.
        • Chiu W.-C.
        • Huang C.-C.
        • Tsai N.-W.
        • Wang H.-C.
        • Lin W.-C.
        • et al.
        HbA1C variability is strongly associated with the severity of peripheral neuropathy in patients with type 2 diabetes.
        Front. Neurosci. 2019; 13
        • Mayeda L.
        • Katz R.
        • Ahmad I.
        • Bansal N.
        • Batacchi Z.
        • Hirsch I.B.
        • et al.
        Glucose time in range and peripheral neuropathy in type 2 diabetes mellitus and chronic kidney disease.
        BMJ Open Diabetes Res. amp; Care. 2020; 8e000991
        • Tesfaye S.
        • Boulton A.J.M.
        • Dyck P.J.
        • Freeman R.
        • Horowitz M.
        • Kempler P.
        • et al.
        Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments.
        Diabetes Care. 2010; 33: 2285-2293
        • Gordois A.
        • Schuffham P.
        • Shirer A.
        • Oglesby A.
        The health care costs of diabetic neuropathy in the United States.
        Diabetes Care. 2003; 26: 1790-1795
        • Lo Z.J.
        • Surendra N.K.
        • Saxena A.
        • Car J.
        Clinical and economic burden of diabetic foot ulcers: a 5-year longitudinal multi-ethnic cohort study from the tropics.
        Int Wound J. 2021; 18: 375-386
        • Nusca A.
        • Tuccinardi D.
        • Albano M.
        • Cavallaro C.
        • Ricottini E.
        • Manfrini S.
        • et al.
        Glycemic variability in the development of cardiovascular complications in diabetes.
        Diabetes/Metab. Res. Rev. 2018; 34e3047
        • Jang J.-Y.
        • Moon S.
        • Cho S.
        • Cho K.H.
        • Oh C.-M.
        Visit-to-visit HbA1c and glucose variability and the risks of macrovascular and microvascular events in the general population.
        Sci. Rep. 2019; 9: 1-8
        • Kaur R.
        • Kaur M.
        • Singh J.
        Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies.
        Cardiovasc. Diabetol. 2018; 17: 1-17
        • Y-p Liu
        • S-j Shao
        • Guo H.-d
        Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy.
        Life Sci. 2020; 248117459
        • Maruhashi T.
        • Higashi Y.
        Pathophysiological association between diabetes mellitus and endothelial dysfunction.
        Antioxidants. 2021; 10: 1306
        • Callaghan B.C.
        • Little A.A.
        • Feldman E.L.
        • Hughes R.A.
        Enhanced glucose control for preventing and treating diabetic neuropathy.
        Cochrane Database Syst. Rev. 2012;
        • Control D.
        • Group C.T.R.
        The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial.
        Diabetes. 1995; 44: 968-983
        • Ceriello A.
        • Ihnat M.
        ‘Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting.
        Diabet. Med. 2010; 27: 862-867
        • Jun J.E.
        • Jin S.-M.
        • Baek J.
        • Oh S.
        • Hur K.Y.
        • Lee M.-S.
        • et al.
        The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes.
        Cardiovasc. Diabetol. 2015; 14: 1-9
        • Yang C.-P.
        • Lin C.-C.
        • Li C.-I.
        • Liu C.-S.
        • Lin W.-Y.
        • Hwang K.-L.
        • et al.
        Cardiovascular risk factors increase the risks of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: the Taiwan Diabetes Study.
        Medicine. 2015; 94
        • Zhou J.J.
        • Coleman R.
        • Holman R.R.
        • Reaven P.
        Long-term glucose variability and risk of nephropathy complication in UKPDS, ACCORD and VADT trials.
        Diabetologia. 2020; 63: 2482-2485
        • Callaghan B.C.
        • Cheng H.T.
        • Stables C.L.
        • Smith A.L.
        • Feldman E.L.
        Diabetic neuropathy: clinical manifestations and current treatments.
        Lancet Neurol. 2012; 11: 521-534
        • Callaghan B.C.
        • Cheng H.T.
        • Stables C.L.
        • Smith A.L.
        • Feldman E.L.
        Diabetic neuropathy: clinical manifestations and current treatments.
        Lancet Neurol. 2012; 11: 521-534
        • Ge S.
        • Xie J.
        • Zheng L.
        • Yang L.
        • Zhu H.
        • Cheng X.
        • et al.
        Associations of serum anti-ganglioside antibodies and inflammatory markers in diabetic peripheral neuropathy.
        Diabetes Res. Clin. Pract. 2016; 115: 68-75
        • Zhu T.
        • Meng Q.
        • Ji J.
        • Lou X.
        • Zhang L.
        Toll-like receptor 4 and tumor necrosis factor-alpha as diagnostic biomarkers for diabetic peripheral neuropathy.
        Neurosci. Lett. 2015; 585: 28-32
        • Liu S.
        • Zheng H.
        • Zhu X.
        • Mao F.
        • Zhang S.
        • Shi H.
        • et al.
        Neutrophil-to-lymphocyte ratio is associated with diabetic peripheral neuropathy in type 2 diabetes patients.
        Diabetes Res. Clin. Pract. 2017; 130: 90-97
        • Wu F.
        • Jing Y.
        • Tang X.
        • Li D.
        • Gong L.
        • Zhao H.
        • et al.
        Anemia: an independent risk factor of diabetic peripheral neuropathy in type 2 diabetic patients.
        Acta Diabetol. 2017; 54: 925-931
        • Zhao W.
        • Zeng H.
        • Zhang X.
        • Liu F.
        • Pan J.
        • Zhao J.
        • et al.
        A high thyroid stimulating hormone level is associated with diabetic peripheral neuropathy in type 2 diabetes patients.
        Diabetes Res. Clin. Pract. 2016; 115: 122-129
        • Takao T.
        • Matsuyama Y.
        • Yanagisawa H.
        • Kikuchi M.
        • Kawazu S.
        Association between HbA1c variability and mortality in patients with type 2 diabetes.
        J. Diabetes its Complicat. 2014; 28: 494-499
        • Siegelaar S.E.
        • Holleman F.
        • Hoekstra J.B.
        • DeVries J.H.
        Glucose variability; does it matter?.
        Endocr. Rev. 2010; 31: 171-182
        • Chang C.M.
        • Hsieh C.J.
        • Huang J.C.
        • Huang I.C.
        Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus.
        Acta Diabetol. 2012; 49: S171-S177
        • Su J.B.
        • Zhao L.H.
        • Zhang X.L.
        • Cai H.L.
        • Huang H.Y.
        • Xu F.
        • et al.
        HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients.
        Cardiovasc. Diabetol. 2018; 17: 47
        • Akaza M.
        • Akaza I.
        • Kanouchi T.
        • Sasano T.
        • Sumi Y.
        • Yokota T.
        Nerve conduction study of the association between glycemic variability and diabetes neuropathy.
        Diabetol. Metab. Syndr. 2018; 10: 69
        • Pai Y.W.
        • Lin C.H.
        • Lee I.T.
        • Chang M.H.
        Variability of fasting plasma glucose and the risk of painful diabetic peripheral neuropathy in patients with type 2 diabetes.
        Diabetes Metab. 2018; 44: 129-134
        • Yang C.P.
        • Li C.I.
        • Liu C.S.
        • Lin W.Y.
        • Hwang K.L.
        • Yang S.Y.
        • et al.
        Variability of fasting plasma glucose increased risks of diabetic polyneuropathy in T2DM.
        Neurology. 2017; 88: 944-951
        • Siegelaar S.E.
        • Kilpatrick E.S.
        • Rigby A.S.
        • Atkin S.L.
        • Hoekstra J.B.
        • Devries J.H.
        Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT.
        Diabetologia. 2009; 52: 2229-2232
        • Peltier A.
        • Goutman S.A.
        • Callaghan B.C.
        Painful Diabetic Neuropathy.
        BMJ (Clinical research ed). 348. 2014: g1799
        • Brownlee M.
        The pathobiology of diabetic complications.
        A Unifying Mech. 2005; 54: 1615-1625
        • Schisano B.
        • Tripathi G.
        • McGee K.
        • McTernan P.G.
        • Ceriello A.
        Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells.
        Diabetologia. 2011; 54: 1219-1226