Understanding cellular and molecular mechanisms of pathogenesis of diabetic tendinopathy

Table 1 Biomechanical property changes of diabetic tendinopathy

Species	Tendon(s)	Groups	Duration of DM	Biomechanical properties of diabetic tendons	Ref.
Human	Achilles tendon	CG and DG	An average of 14 yr	Significantly less tendon elongation, higher tendon stiffness and hysteresis, and lower tendon forces in DM group during walking compared with CG.	Petrovic et al[23], 2018
Human	Achilles tendon	CG and DG	An average of 13 yr	No significance in maximum force including max force, stiffness, stress, strain, and modulus between DG and CG, but a trend towards reduced tendon strain in DG; significantly higher tendon modulus in common force in DG than in CG.	Couppé et al[24], 2016
Human	Achilles tendon	CG and DG	Stage V type II diabetes patients	Significantly inferior biomechanical properties of diabetic tendons in DG including decreased elasticity (Young′s modulus), maximum load, stiffness, toughness, load at yield point, energy, strain, and elongation at break point, tenacity, and strain at automatic load drop.	Guney et al[17], 2015
Human	Achilles tendon	CG, DG I (with foot ulcer), and DG II (without foot ulcer).	An average of 15 yr in DG I and an average of 6 yr in DG II.	Significantly higher thickness of proximal, medial, and distal third tendon in DG I than in DG II and CG, higher tendon thickness in DG II than in CG but no significance; significantly reduced stiffness of medial and distal third tendon in DG I.	Evranos et al[22], 2015
Male C57Bl/6J mice	FDL tendon	CG (low fat diet) and DM (high fat diet)	High or low-fat diet for 48 wk; at 12, 24, and 48 d post-injury.	Significantly decreased tendon range of motion at 40 and 48 wk in high fat diet group relative to low fat diet group; reduced max load at failure at 48 wk and increased stiffness at 24 wk in high fat diet group.	Studentsova et al[30], 2018
Male C57Bl/6J mice	FDL tendon	CG (low fat diet) and DM (high fat diet)	High or low-fat diet for 12 wk; at 10, 14, 21, and 28 d post-diet initiation.	Significantly lower maximum load, yield load, and energy to maximum force of tendon in DM compared with CG at 28 d; no differences in stiffness between the two groups.	Ackerman et al[31], 2017
Male C57BL/KsJ (db/db) mice	Achilles tendon	CG and DG	16 wk of DM	Significantly decreased maximum load, elastic modulus, maximum stress, and stiffness of tendons in DG; no significance in tensile strain.	Boivin et al[16], 2014
db/db Diabetic mice and db/+ non-diabetic heterozygous control mice	Supraspinatus, Achilles, and patellar tendons.	CG and DG	60 days for DM	Significantly reduced stiffness at the insertion site of tendons in DG for all three tendons and reduced modulus at the insertion site of Achilles tendons in DG; no significance in stiffness or modulus of mid-substance in any tendon between DG and CG.	Connizzo et al[33], 2014
Male C57BL/6J mice	FDL tendon	CG (low fat diet) and DG (high fat diet)	High or low-fat diet for 12 wk for uninjured tendons; high or low-fat diet for 24 wk for injured tendons, at 7, 14, and 28 d post-injury.	No significance in biomechanical parameters including maximum force, work to maximum force, and stiffness of uninjured FDL tendon at 12 wk; reduced maximum force of uninjured FDL tendon at 24 wk; significantly decreased biomechanical parameters of injured tendons in DG at 28 d.	David et al[32], 2014
Wistar rats	Achilles tendon	CG and DG	4 wk post-induction; 3 wk post-operation.	No significance in ultimate load, ultimate elongation, stiffness, ultimate strength, ultimate strain, elastic modulus, and cross-sectional area.	de Oliveira et al[36], 2019
Wistar rats	Achilles tendon	CG and DG	5 wk post-induction	Significantly increased elastic modulus and maximum tension, reduced transverse area in DG; no significance in maximum strength between DG and CG.	Bezerra et al[27], 2016
SD rats	Achilles and tail tendon	CG, acute DG (1 wk), and chronic DG (10 wk)	10 wk post-induction	No significance in biomechanical properties of Achilles and tail tendons between groups, including maximum force, deformation, stiffness, stress, strain, and Young’s modulus.	Volper et al[12], 2015
Wistar rats	Achilles tendon	CG and DG	30 d post-induction; at days 10 post-surgery.	Significantly decreased stress tensile load and Young's modulus of stiffness of tendons in DG than in CG.	Mohsenifar et al[20], 2014
ZDSD and control rats (CD: SD-derived)	Tail tendon	CG and DG	High fat diet for 12 wk	Significantly higher nanoscale modulus at tendon fibrils level in DG and more variable compared with CG; at the fascicle level, no significance in mechanical properties between DG and CG; at the material level, significantly greater ultimate stress and modulus in DG tendon than in CG.	Gonzalez et al[28], 2014
SD rats	Supraspinatus tendon	Hyperglycemia group and control group	8 wk following hyperglycemia induction	No significance in stiffness and modulus at both the insertion site and mid-substance of tendon between hyperglycemia group and control group.	Thomas et al[35], 2014
Lewis rats	Achilles tendon	CG and DG	5 d post-induction	Significantly reduced maximum tensile load of tendon in DG.	Lehner et al[19], 2012
Male diabetic GK rats and control Wistar rats	Achilles tendon	CG and DG	1 year of DM; at 14 d post-rupture.	No significance in biomechanical properties as peak load, energy at peak load and stress, except for lower stiffness of intact tendons in DG; lower stiffness of injured tendons in DG compared with the injured tendons in CG.	Ahmed et al[21], 2012
Wistar rats	Achilles tendon	CG and DG	70 d post-induction	Significantly decreased elastic modulus of tendon in DG; increased specific deformation, deformation at maximum force and energy/tendon area of tendon in DG.	de Oliveira et al[26], 2012
Wistar rats	Achilles tendon	CG and DG	70 d post-induction	Significantly decreased elastic modulus of tendon in DG; increased specific strain, maximum strain and energy/tendon area of tendon in DG.	de Oliveira et al[25], 2011
Lewis rats	Patellar tendon	CG and DG	12- and 19-d post-induction	Significantly reduced Young′s modulus of tendon in DG at both time points.	Fox et al[15], 2011
Lewis rats	Supraspinatus tendon	CG and DG	1 and 2 wk post-operation	Significantly reduced mean load-to-failure and stiffness of tendon-bone complex in DG at both time points.	Bedi et al[34], 2010
New Zealand rabbits	Achilles tendon	Non-glycated group and glycated group	60 d following glycation	Significant increase in maximum load, Young′s modulus of elasticity, energy to yield, and toughness of glycated tendon.	Reddy et al[29], 2003

FDL: Flexor digitorum longus; CG: Control group; DG: Diabetes group; DM: Diabetes mellitus; SD: Sprague-Dawley; ZDSD: Zucker diabetic SD; GK: Goto-Kakizaki.