Diabetic Neuropathy Assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy

Abstract

Background Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy. Aim: To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications.

Materials and methods Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered.

Results Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35–6.49], p=0.007), nephropathy (OR 6.25 [3.21–12.15]; p=6.7×10–8) and macrovascular disease (OR 2.72 [1.50–4.93], p=0.001).

Conclusions Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.

Key Words

Type 1 diabetes - diabetic complications - multifrequency vibrometry - diabetic neuropathy - diabetic retinopathy - diabetic nephropathy

Publikationsverlauf

Eingereicht: 03. Juli 2022
Eingereicht: 01. Dezember 2022

Angenommen: 05. Januar 2023

Accepted Manuscript online:
10. Januar 2023

Artikel online veröffentlicht:
16. Februar 2023

• References

• 1 Ahsan H. Diabetic retinopathy – biomolecules and multiple pathophysiology. Diabetes Metab Syndr 2015; 9: 51-54
• 2 Babizhayev MA, Strokov IA, Nosikov VV. et al. The role of oxidative stress in diabetic neuropathy: Generation of free radical species in the glycation reaction and gene polymorphisms encoding antioxidant enzymes to genetic susceptibility to diabetic neuropathy in population of type I diabetic patients. Cell Biochem Biophys 2015; 71: 1425-1443
• 3 Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005; 54: 1615-1625
• 4 Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neuropathy: Where are we now and where to go?. J Diabetes Investig 2011; 2: 18-32
• 5 Morgan CL, Currie CJ, Stott NC. et al. The prevalence of multiple diabetes-related complications. Diabet Med 2000; 17: 146-151
• 6 Maser RE, Steenkiste AR, Dorman JS. et al. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes. 1989; 38: 1456-1461
• 7 Wilkinson CP, Ferris FL, Klein RE. et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110: 1677-1682
• 8 Toto RD. Microalbuminuria: Definition, detection, and clinical significance. J Clin Hypertens (Greenwich) 2004; 6: 2-7
• 9 Pop-Busui R, Boulton AJ, Feldman EL. et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 2017; 40: 136-154
• 10 Braffett BH, Gubitosi-Klug RA, Albers JW. et al. Risk factors for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study. Diabetes 2020; 69: 1000-1010
• 11 Ekman L, Thrainsdottir S, Englund E. et al. Evaluation of small nerve fiber dysfunction in type 2 diabetes. Acta Neurol Scand 2020; 141: 38-46
• 12 Lindholm E, Londahl M, Fagher K. et al. Strong association between vibration perception thresholds at low frequencies (4 and 8 Hz), neuropathic symptoms and diabetic foot ulcers. PLoS One 2019; 14: e0212921
• 13 Ising E, Dahlin LB, Elding Larsson H. Impaired vibrotactile sense in children and adolescents with type 1 diabetes – Signs of peripheral neuropathy. PLoS One 2018; 13: e0196243
• 14 Dahlin LB, Elgzyri T, Londahl M. et al. Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients. Acta Diabetol 2019;
• 15 Harding JL, Pavkov ME, Magliano DJ. et al. Global trends in diabetes complications: A review of current evidence. Diabetologia 2019; 62: 3-16
• 16 Andersen AR, Christiansen JS, Andersen JK. et al. Diabetic nephropathy in type 1 (insulin-dependent) diabetes: An epidemiological study. Diabetologia 1983; 25: 496-501
• 17 Sabanayagam C, Yip W, Ting DS. et al. Ten emerging trends in the epidemiology of diabetic retinopathy. Ophthalmic Epidemiol 2016; 23: 209-222
• 18 Nordwall M, Bojestig M, Arnqvist HJ. et al. Declining incidence of severe retinopathy and persisting decrease of nephropathy in an unselected population of Type 1 diabetes-the Linkoping Diabetes Complications Study. Diabetologia 2004; 47: 1266-1272
• 19 Ekman L, Lindholm E, Brogren E. et al. Normative values of the vibration perception thresholds at finger pulps and metatarsal heads in healthy adults. PLoS One 2021; 16: e0249461
• 20 Bril V, Tomioka S, Buchanan RA. et al. Reliability and validity of the modified Toronto Clinical Neuropathy Score in diabetic sensorimotor polyneuropathy. Diabet Med 2009; 26: 240-246
• 21 Lindholm E, Ekman L, Apelqvist J. et al. 55(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Barcelona, Spain, 16 – 20 September 2019. Diabetologia 2019; 62: S471-S471
• 22 Klessens CQ, Woutman TD, Veraar KA. et al. An autopsy study suggests that diabetic nephropathy is underdiagnosed. Kidney Int 2016; 90: 149-156
• 23 Bojestig M, Arnqvist HJ, Hermansson G. et al. Declining incidence of nephropathy in insulin-dependent diabetes mellitus. N Engl J Med 1994; 330: 15-18
• 24 Nitoda E, Kallinikos P, Pallikaris A. et al. Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy. Curr Eye Res 2012; 37: 898-906
• 25 Gerhardsson L, Gillstrom L, Hagberg M. Test-retest reliability of neurophysiological tests of hand-arm vibration syndrome in vibration exposed workers and unexposed referents. J Occup Med Toxicol 2014; 9: 38
• 26 Ekman L, Persson Lofgren J, Dahlin LB. Examining practice effects in repeated measurements of vibration perception thresholds on finger pulps of healthy individuals – Is it possible to improve your results over a clinically relevant test interval?. PLoS One 2019; 14: e0226371