Diabetes has been associated with greater risk of complications and prolonged postoperative recovery following ankle trauma. Our cohort study reviewed the operative management and outcomes of ankle fractures in diabetic adults relative to non-diabetic adults from Jan 2016–2019. Non-diabetic controls were frequency age-matched 2:1. 34 of 572 ankle fracture presentations were in diabetic patients, 32% managed non-operatively compared to 29% of the matched non-diabetic cohort. The distribution in Lauge-Hansen fracture pattern was comparable between cohorts. Mean length of follow-up was significantly longer for diabetics (26 weeks) compared to non-diabetics (16 weeks). Post-operative wound complications (superficial wound infection, breakdown, dehiscence) occurred in 48% of the operated diabetic ankles, compared to 5% in non-diabetics (RR 8.1, 95% CI 2.5–26.4). Reoperation (RR 4.3, 95% CI 2.5–26.4, p=0.03) and non-wound complication rates (Charcot joint, mal/non-union, metalware infection) were likewise significantly higher (RR 3.9, 95% CI 1.4–10.8, p=0.008) in diabetics. Amongst diabetics alone, those with an HbA1c >69 mmol/mol (n=14, 41%) demonstrated a significantly higher rate still of non-wound complications (RR 4.3, 95% CI 1.1–18., p=0.03) with a trend towards higher wound complication rates (RR 3, 95% CI 0.52–17, p=0.13). Poorly controlled diabetes is associated with substantially greater complication rates following ankle fracture than those with well controlled or normal blood sugar; high HbA1c > 69mmol/mol is a significant predictor of complicated follow-up. Locally we recommend management strategies that are influenced by the fracture pattern stability and the presence or absence of complicated or poorly managed diabetes

Total knee replacement (TKR) is an effective method of treating end-stage arthritis of the knee. It is not, however, a procedure without risk due to a number of factors, one of which is diabetes mellitus. The purpose of this study was to estimate the general prevalence of diabetes in patients about to undergo primary TKR and to determine whether diabetes mellitus adversely affects the outcome. We conducted a systematic review and meta-analysis according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The Odds Ratio (OR) and mean difference (MD) were used to represent the estimate of risk of a specific outcome. Our results showed the prevalence of diabetes mellitus among patients undergoing TKR was 12.2%. Patients with diabetes mellitus had an increased risk of deep infection (OR = 1.61, 95% confidence interval (CI), 1.38 to 1.88), deep vein thrombosis (in Asia, OR = 2.57, 95% CI, 1.58 to 4.20), periprosthetic fracture (OR = 1.89, 95% CI, 1.04 to 3.45), aseptic loosening (OR = 9.36, 95% CI, 4.63 to 18.90), and a poorer Knee Society function subscore (MD = -5.86, 95% CI, -10.27 to -1.46). Surgeons should advise patients specifically about these increased risks when obtaining informed consent and be meticulous about their peri-operative care. Cite this article: Bone Joint J 2014;96-B:1637–43

Diabetes mellitus is recognised as a risk factor for carpal tunnel syndrome. The response to treatment is unclear, and may be poorer than in non-diabetic patients. Previous randomised studies of interventions for carpal tunnel syndrome have specifically excluded diabetic patients. The aim of this study was to investigate the epidemiology of carpal tunnel syndrome in diabetic patients, and compare the outcome of carpal tunnel decompression with non-diabetic patients. The primary endpoint was improvement in the QuickDASH score. The prevalence of diabetes mellitus was 11.3% (176 of 1564). Diabetic patients were more likely to have severe neurophysiological findings at presentation. Patients with diabetes had poorer QuickDASH scores at one year post-operatively (p = 0.028), although the mean difference was lower than the minimal clinically important difference for this score. After controlling for underlying differences in age and gender, there was no difference between groups in the magnitude of improvement after decompression (p = 0.481). Patients with diabetes mellitus can therefore be expected to enjoy a similar improvement in function

We compared the clinical and radiographic results of total ankle replacement (TAR) performed in non-diabetic and diabetic patients. We identified 173 patients who underwent unilateral TAR between 2004 and 2011 with a minimum of two years’ follow-up. There were 88 male (50.9%) and 85 female (49.1%) patients with a mean age of 66 years (. sd. 7.9, 43 to 84). There were 43 diabetic patients, including 25 with controlled diabetes and 18 with uncontrolled diabetes, and 130 non-diabetic patients. The clinical data which were analysed included the Ankle Osteoarthritis Scale (AOS) and the American Orthopaedic Foot and Ankle Society (AOFAS) scores, as well the incidence of peri-operative complications. The mean AOS and AOFAS scores were significantly better in the non-diabetic group (p = 0.018 and p = 0.038, respectively). In all, nine TARs (21%) in the diabetic group had clinical failure at a mean follow-up of five years (24 to 109), which was significantly higher than the rate of failure of 15 (11.6%) in the non-diabetic group (p = 0.004). The uncontrolled diabetic subgroup had a significantly poorer outcome than the non-diabetic group (p = 0.02), and a higher rate of delayed wound healing. . The incidence of early-onset osteolysis was higher in the diabetic group than in the non-diabetic group (p = 0.02). These results suggest that diabetes mellitus, especially with poor glycaemic control, negatively affects the short- to mid-term outcome after TAR. Cite this article: Bone Joint J 2014;96-B:1674–80

Patients living with type 1 diabetes mellitus (T1DM) can develop early onset osteoporosis and are exposed to an increased risk of fracture. Skeletal health can be influenced easily with diet and exercise. However, diabetes mellitus (DM)-related osteopathy is not emphasized in the public information campaigns on the American Diabetes Association, Diabetes UK, Diabetes Ireland or International Diabetes Federation websites. This investigation aims to assess the perceptions of patients regarding living with T1DM and their baseline knowledge on DM-related osteopathy. A survey was administered to 102 consenting individuals living with T1DM in attendance at the Galway University Hospital Diabetes Centre. Of the respondents, 44% were female and 56% male (mean age of 43). Respondents had T1DM for a mean of 21 years. Participants were asked to identify DM-related complications, including bone thinning and bone fractures. Respondents were primarily concerned about developing DM-related blindness, kidney damage and amputations, but not osteopathy. 49% of respondents did not identify osteopathy as a potential DM-related complication, 28% of respondents related DM with bone thinning and bone fractures, and 22% individuals only identified bone thinning or bone fractures. When asked for their primary source of DM-related information, endocrinologists and internet where identified. When comparable questions were asked of DM-related healthcare professionals, 56% did not recognize osteopathy as a complication of T1DM. This study demonstrated a low-level awareness of the impact living with T1DM has on bone health. The deployment of patient-interactive activities or educational modules may enhance the future health of individuals living with T1DM

Introduction. There are nearly 500,000 people with undiagnosed diabetes mellitus in the UK. The incidental finding vascular calcification on plain radiographs in patients with undiagnosed diabetes has the potential to alter patient management in those presenting with pathology. We hypothesised that the presence of vascular calcification on plain radiographs of the foot may predict the diagnosis of diabetes. The primary aim of this case control study was to determine the positive predictive value of vascular calcification to diagnose diabetes. Secondary aims were to determine the odds of having diabetes dependent on other known risk factors for calcification. Methods. A retrospective case control study of 130 diabetic patients were compared to 130 non-diabetic patients that were matched for age and gender. The presence of vascular calcification in anterior, posterior or plantar vessels, and length of calcification were measured on plain radiographs. McNemar's Chi-squared test and positive predictive values were calculated. Conditional logistic regression models were used to estimate the association between calcification and diabetes. Results. 28 patients had type I diabetes and 102 had type II diabetes. The mean age was 58.0 in both groups and 31.5% were females. 89.2% of those with diabetes had calcification present, and 23.1% in those without (p < 0.0001). Calcification in two vessels predicts diabetes with a positive predictive value of 91.2% (95% CI 82.1%–100%). The odds ratio for having diabetes is 78 (95% CI: 7.8 – 784) times higher in a person who has calcification in the blood vessels of their foot than in a person without calcification after adjusting for confounders. Conclusion. This study has demonstrated that vascular calcification in 2 vessels is over 90% predictive of a diagnosis of diabetes. This screening test could be used in future clinics when interpreting radiographs, aiding in the diagnosis of diabetes and altering patient management

Background. Ankle fractures associated with diabetes experience more complications following standard Open-Reduction-Internal-Fixation (ORIF) than those without diabetes. Augmented fixation strategies namely extended ORIF and hind-foot-nail (HFN) may offer better results, and early weightbearing in this group. The aim of this study was to define the population of patients with diabetes undergoing primary fixation for ankle fractures. Secondarily, to assess the utilisation of standard and augmented strategies and the effect of these choices on surgical outcomes including early post-operative weight bearing and surgical complications. Methods. A national-multicentre retrospective cohort study was conducted between January to June 2019 in 56 centres (10 Major- Trauma-Centres and 46 Trauma-Units) in the United Kingdom; 1360 specifically defined complex ankle-fractures were enrolled. Demographics, fixation choice, surgical and functional outcomes were recorded. Statistical analysis was performed to compare high-risk patients with/without diabetes. Results. There were 316 patients in the diabetes cohort with mean age 63.9yrs (vs. 49.3yrs in non-diabetes cohort), and greater frailty score >4 (24% vs.14% (non-diabetes cohort) (p<0.03); 7.5% had documented neuropathy. In the diabetes cohort, 79.7% underwent standard ORIF, 7.1% extended ORIF and 10.2% a HFN compared to 87.7%, 3.0% and 10.3% in the non-diabetes cohort. Surgical wound complications after standard-ORIF were higher in the diabetes cohort (15.1% vs. 8.7%) (p<0.02) but patients with diabetes who underwent augmented techniques showed little difference in surgical outcomes/complications to non-diabetes, even though early-weight- bearing rates were greater than standard-ORIF. Conclusion. Ankle fractures in diabetes occur in older, frailer patients; whilst lower than expected neuropathy rates suggest a need for improved assessment. Augmented surgical techniques may allow earlier weight-bearing without increasing complications in keeping with modern guidelines in ankle fracture management

Introduction. A common acute orthopaedic presentation is an ulcerated or infected foot secondary to diabetic neuropathy. Surgical debridement or amputation are often required to manage this complication of diabetes. International literature indicates that amputation may lead to further complications and an increased mortality rate. The aim of this study is to investigate the mortality rate associated with different surgical interventions. This will inform surgical management of patients presenting with acute foot complications from diabetes. Methods. This is a retrospective review of patients with diabetic foot infections aged >16 years attending Middlemore Hospital over a 10-year period (2012–2021). Clinical records were examined to determine whether patients were managed with no surgery, surgery but not amputation, or amputation. We recorded relevant baseline characteristics and comorbidities. Regression models were used to determine factors associated with mortality. Results. Over the study period, 1260 patients were included in analysis. Patients were divided into three groups, a control group who received no surgical intervention (n=554), those receiving surgery but not amputation (n=269), and those who underwent amputation (n=437). After adjustment for potential confounders, mortality rates were significantly higher in those who underwent amputation compared with those who received surgical intervention without amputation. Survival probability at 1 year and 5 years was highest in the surgical intervention but not amputation group. Conclusion. It is clinically important that there is a lower mortality rate in patients who undergo surgical intervention without amputation. Treatment that aims to salvage the limb rather than amputate should be considered in management of patients with diabetic foot complications to optimise their care

Introduction and Objective. Type 2 diabetes mellitus (T2DM), and the often concurrent obesity, causes metabolic changes that affect many organs and tissues, including bone. Despite a normal or even higher bone mineral density (BMD), T2DM has often been associated with a higher fracture risk, indicating a compromised bone quality. In this work, we use a novel congenic leptin receptor-deficient BioBreeding Diabetes Resistant rat (BBDR.cg.lepr.cp) to investigate the impact of T2DM and obesity on bone morphology and architecture at the microscale. Materials and Methods. Two different anatomical locations, i.e., femur and cranium, were studied combining micro-computed X-ray tomography (micro-CT) with scanning electron microscopy (SEM). Micro-CT data were examined using advanced image analysis tools in three-dimensions (3D). Results. Both parietal bones and femurs were smaller, i.e., thinner and shorter, respectively, in diabetic animals compared to healthy controls. Image analysis of the sagittal suture revealed a reduced suture width and length in diabetic animals, suggesting an altered bone apposition rate. Histomorphometry analysis from micro-CT data highlighted differences in microstructure of both trabecular and cortical femur between diabetic and healthy rats. In particular, bone volume fraction (BV/TV) was lower in the T2DM group, while trabecular spacing (Tb.Sp) was increased, overall indicating a higher porosity in diabetic trabecular bone. SEM revealed the presence of extended portions of hyper-mineralized cartilage in the distal femur of the diabetic animals. Conclusions. Micro-CT analyses, combined with SEM imaging, suggest that T2DM impacts bone growth and remodelling, in turn leading to differences in the structural organization at the microscale

We have evaluated the extent to which diabetes affects the revision rate following total hip replacement (THR). Through the Danish Hip Arthroplasty Registry we identified all patients undergoing a primary THR (n = 57 575) between 1 January 1996 and 31 December 2005, of whom 3278 had diabetes. The presence of diabetes among these patients was identified through the Danish National Registry of Patients and the Danish National Drug Prescription Database. We estimated the relative risk for revision and the 95% confidence intervals for patients with diabetes compared to those without, adjusting for the confounding factors. Diabetes is associated with an increased risk of revision due to deep infection (relative risk = 1.45 (95% confidence interval 1.00 to 2.09), particularly in those with type 2 diabetes (relative risk = 1.49 (95% confidence interval 1.02 to 2.18)), those with diabetes for less than five years prior to THR (relative risk = 1.69 (95% confidence interval 1.24 to 2.32)), those with complications due to diabetes (relative risk = 2.11 (95% confidence interval 1.41 to 3.17)), and those with cardiovascular comorbidities prior to surgery (relative risk = 2.35 (95% confidence interval 1.39 to 3.98)). Patients and surgeons should be aware of the relatively elevated risk of revision due to deep infection following THR in diabetes particularly in those with insufficient control of their glucose level

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373–378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1

Abstract. Objectives. Diabetes has been associated with greater risk of complications and prolonged postoperative recovery following ankle trauma. Our cohort study seeks to review the operative management and outcomes of ankle fractures in diabetic adults relative to non-diabetic adults. Methods. Cases were identified using ICD-10 coding criteria. 572 patients from Jan 2016–2019 presented with ankle fractures; 34 in diabetic patients. Mechanism of injury and stability were determined from the index radiograph using a validated Lauge-Hansen classification algorithm. Admission, primary post-operative and discharge radiographs were reviewed independently by two foot and ankle reconstruction specialists to assess adequacy of fixation method. 32% of diabetic patients were managed non-operatively compared to 29% of the matched non-diabetic cohort. The distribution in Lauge-Hansen fracture pattern was comparable between cohorts. Non-diabetic controls were frequency age-matched 2:1. Results. Mean length of follow-up was significantly longer for diabetics (26 weeks) compared to non-diabetics (16 weeks). Post-operative wound complications (superficial wound infection, breakdown, dehiscence) occurred in 48% of the operated diabetic ankles, compared to 5% in non-diabetics (RR 8.1, 95% CI 2.5–26.4). Reoperation (RR 4.3, 95% CI 2.5–26.4, p=0.03) and non-wound complication rates (Charcot joint, mal/non-union, metalwork infection) were likewise significantly higher (RR 3.9, 95% CI 1.4–10.8, p=0.008) in diabetics. Amongst diabetics alone, those with an HbA1c >69 mmol/mol (n=14, 41%) demonstrated a significantly higher rate still of non-wound complications (RR 4.3, 95% CI 1.1–18., p=0.03) with a trend towards higher wound complication rates (RR 3, 95% CI 0.52–17, p=0.13). Conclusions. Poorly controlled diabetes is associated with substantially greater complication rates following ankle fracture than those with well controlled or normal blood sugar; high HbA1c > 69mmol/mol is a significant predictor of complicated follow-up. Locally we recommend management strategies that are influenced by the fracture pattern stability and the presence or absence of complicated or poorly managed diabetes. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Total hip replacement (THR) has been shown to be a cost-effective procedure. However, it is not risk-free. Certain conditions, such as diabetes mellitus, are thought to increase the risk of complications. In this study we have evaluated the prevalence of diabetes mellitus in patients undergoing THR and the associated risk of adverse operative outcomes. A meta-analysis and systematic review were conducted according to the guidelines of the meta-analysis of observational studies in epidemiology. Inclusion criteria were observational studies reporting the prevalence of diabetes in the study population, accompanied by reports of at least one of the following outcomes: venous thromboembolic events; acute coronary events; infections of the urinary tract, lower respiratory tract or surgical site; or requirement for revision arthroplasty. Altman and Bland’s methods were used to calculate differences in relative risks. The prevalence of diabetes mellitus was found to be 5.0% among patients undergoing THR, and was associated with an increased risk of established surgical site infection (odds ratio (OR) 2.04 (95% confidence interval (CI) 1.52 to 2.76)), urinary infection (OR 1.43 (95% CI 1.33 to 1.55)) and lower respiratory tract infections (OR 1.95 (95% CI 1.61 to 2.26)). Diabetes mellitus is a relatively common comorbidity encountered in THR. Diabetic patients have a higher rate of developing both surgical site and non-surgical site infections following THR. Cite this article: Bone Joint J 2013;95-B:1474–9

Aim. This retrospective case series reports the reoperation, major amputation, survival rates and mobility status in diabetic patients who underwent a trans-metatarsal amputation (TMA) managed within a multi-disciplinary diabetic foot care service. Methods and patients. Forty-one consecutive patients (37 men, 4 women) underwent a TMA between January 2008 to December 2017. They were retrospectively reviewed. The mean age at the time of surgery was 63 years (range 39 – 92). Results. Eighty-eight per cent (36/41) of the patients were followed-up. Four (11%) of the 36 patients required reoperation, including three major amputations (8%). All the patients requiring a reoperation were vasculopaths. The four-year patient survival rate following a TMA was 69% (25/36). Ninety-six per cent (21/22) of the surviving patients not requiring revision to a major amputation were fully mobile in bespoke orthoses, of whom a third required a stick. Conclusion. This study shows that transmetatarsal amputation in patients with diabetes, managed in a multi-disciplinary diabetic foot care service, is effective for limb salvage

We reviewed 87 patients who had undergone expansive cervical laminoplasty between 1999 and 2005. These were divided into two groups: those who had diabetes mellitus and those who did not. There were 31 patients in the diabetes group and 56 in the control group. Although a significant improvement in the Japanese Orthopaedic Association score was seen in both groups, the post-operative recovery rate in the control group was better than that of the diabetic group. The patients’ age and symptom duration adversely affected the rate of recovery in the diabetic group only. Smoking did not affect the outcome in either group. A logistic regression analysis found diabetes and signal changes in the spinal cord on MRI to be significant risk factors for a poor outcome (odds ratio 2.86, 3.02, respectively). Furthermore, the interaction of diabetes with smoking and/or age increased this risk. We conclude that diabetes mellitus, or the interaction of this with old age, can adversely affect outcome after cervical laminoplasty. However, smoking alone cannot be regarded as a risk factor

Fragility fractures are skeletal complications associated with type 2 diabetes (T2D) causing disability, hospitalization, impaired quality of life, and increased mortality. Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk. We have recently shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone formation in T2D. We hypothesized that Wnt/B- catenin target genes are down-regulated in bone of T2D subjects as a consequence of decreased SOST and AGEs accumulation. To this end, we studied gene expression in extracts of bone samples obtained from femoral heads of 14 subjects with relatively well-controlled T2D (HbA1c 6.5±1.7%) and 21 control, non-diabetic postmenopausal women (age >65 years) undergoing hip replacement. There were no differences in age (73.2± .8 vs. 75.2±8.5 years) or BMI (27.7±5.6 vs. 29.9±5.4 kg/m2) between control and T2D groups, respectively. Expression of LEF1 mRNA was significantly lower in T2D compared to non-diabetic subjects (p=0.002), while DKK1 was not different between groups (p=0.108). Correlation analysis showed that DKK1 (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) increased with age in T2D. COL1A1 mRNA trended lower in T2D compared to controls (p=0.056). Bone volume (9,333 ± 1,443 vs. 15,53 ± 2,442 mm2; p=0.048), mineralized volume (9,278 ± 1,418 vs. 15,45 ± 2,444 mm. 2. ; p=0.048) and BV/TV (0,2125 ± 0,03114 vs. 0,3719 ± 0,03196 %; p=0.002) measured by bone histomorphometry were lower in T2D compared to controls. Our data show that even in patients with relatively good glycemic control, T2D decreases expression of Wnt/B-catenin target genes andCOL1A1, associated with decreased bone density. These results may help understand the mechanisms underlying bone fragility in T2D

Introduction: As a consequence of the rising prevalence of diabetes worldwide, an increasing proportion of diabetic THR patients may be expected in coming years. Diabetes research on postoperative complications among arthroplasty patients is limited. We evaluated the extent to which diabetes affect the revision rate due to aseptic loosening, deep infection and dislocation following total hip arthroplasty (THA). Material and Methods: We used the Danish Hip Arthroplasty Registry (DHR) to identify all primary THR patients operated on during the period from 1 January 1996 to 31 December 2005. The presence of diabetes among THA patients was identified by using The Danish National Registry of Patients and The Danish National Drug Prescription Database. We used Poisson regression analyses, to estimate relative risk (RR) and 95% Confidence Interval (CI) for patients with diabetes compared to patients without diabetes, both crude and adjusted for potentially confounding factors. Results: We identified 57 575 first primary THR patients in DHR, of which 3 278 (5.7%) were with diabetes and 54 297 (94.3%) without diabetes. An adjusted RR for revision due to deep infection of 1.45 (CI: 1.00–2.09) was found for THA diabetic patients compared to patients without diabetes. The RR was particularly high for THA patients with diabetes less than five years (RR was 1.71 (CI: 1.24–32.34), with the presence of diabetes related comorbidites prior THA (RR was 2.35 (CI: 1.39–3.98) and diabetes related complications (RR was 1.88 (CI: 1.17–3.03). Conclusion. The patient and the surgeon should be aware of the relative increased risk of revision due to deep infection following THA as compared with the risk in THA patients without diabetes

Intervertebral disc degeneration (IDD) is a major cause of low back pain, which affects 80% of the adult population at least once in their life. The pathophysiological conditions underlying IDD are still poorly understood. Genetic makeup, aging, smoking, physical inactivity and mechanical overloading, especially due to obesity, are among the strongest risk factors involved. Moreover, IDD is often associated with chronic inflammation within disc tissues, which increases matrix breakdown, glycosaminoglycan (GAG) loss and cell death. This micro-inflammatory environment is typical of several metabolic disorders, including diabetes mellitus (DM). As the etiopathogenesis of IDD in diabetic subjects remains scarcely understood, we hypothesised that this may be driven by a DM-induced inflammation leading to a combination of reduced GAG levels, decreased proteoglycan synthesis and increased matrix breakdown within the disc. The objective of the study was to investigate the pathogenesis of IDD in a murine model of type 1 DM (T1DM), namely non-obese diabetic (NOD) mouse. Total disc glycosaminoglycan (GAG) content, proteoglycan synthesis, aggrecan fragmentation mediated by matrix metalloproteinases (MMPs) and a Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS), glucose transporter (mGLUT1) gene expression and apoptosis (TUNEL assay) were assessed in NOD mice and wild-type euglycemic control mice. Spinal structural and molecular changes were analysed by micro-computed tomography (mCT), histological staining (Safranin-O and fast green) and quantitative immunofluorescence (anti-ADAMTS-4 and 5 antibodies). Statistical analysis was conducted considering the average of 35 samples ± standard error for each measurement, with 95% confidence intervals calculated to determine statistical significance (p-value < 0.05). IVDs of NOD mice showed increased disc apoptosis (p < 0.05) and higher aggrecan fragmentation mediated by ADAMTS (p < 0.05). However, ADAMTS-4 and −5 did not appear to be involved in this process. The total GAG content normalized to DNA and PG synthesis showed no statistically significant alterations, as well as Safranin O staining. Although not significantly, NOD mice showed reduced glucose uptake. In addition, the vertebral structure of NOD mice at mCT seemed not to be altered. These data demonstrate that DM may contribute to IDD by increasing aggrecan degradation and promoting cell apoptosis, which may represent early indicators of the involvement of DM in the pathogenesis of IDD

Introduction. Tendon disease and rupture are common in patients with diabetes and these are exacerbated by poor healing. although nanoscale changes in diabetic tendon are linked to increased strength and stiffness. The resistance to mechanical damage of a tissue may be measured using fatigue testing but this has not been carried out in diabetic tendon, although the toughness of diabetic bone is known to be reduced. The aim of this study was to measure the static fatigue behaviour of tendons from a streptozotocin (STZ)-induced rat model of diabetes, hypothesising that diabetes causes tendon to show lower resistance to mechanical damage than healthy tendon. Materials and Methods. Diabetic (n=3, 12 weeks post-STZ) and age-matched control (n=3) adult male Sprague Dawley rats were culled, tails harvested and stored at −80ºC. Following defrosting, fascicles (5 per animal) were carefully dissected, mean diameter measured using an optical micrometer and mounted in a Bose Biodynamics test machine using custom grips in a PBS bath. Static fatigue testing at 30 MPa to failure enabled both elastic modulus (initial ramp) and steady state creep rate (gradient at creep curve inflexion) to be measured. Data are reported as median ± interquartile range and pw0.05 using a Mann-Whitney U test was taken as significant. Results. Confirming previous reports, tendon from diabetic rats showed significantly higher elastic modulus (201 ± 68 MPa) than healthy (151 ± 62 MPa). Strain at failure showed no differences between groups. Tendon from diabetic rats showed significantly slower steady state creep (71 ± 44 μstrain s. −1. ) than healthy (691 ± 1000 μstrain s. −1. ). Discussion. These preliminary data show an order of magnitude larger resistance to mechanical damage in diabetic tendons, possibly associated with the previously reported increased packing and decreased fibril diameters. Energy-storing flexor tendons, the most commonly affected in diabetics, and the positional tendons tested here show similar fatigue behaviour when tested at the same fraction of “stress-in-life”. Further investigation is required into the cell tissue repair response in diabetes in order to link reduced rates of mechanical damage with the clinically increased risk of disease and rupture in diabetic patients