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

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

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Background and aims:

T2D is postulated to be an important aetiological factor for lumbar disc degeneration (LDD), which itself has a well documented relationship with low back pain. Obesity increases risk of both T2D, low back pain and LDD. Connective tissue modification has been reported in hyperglycaemia, but the epidemiology of LDD in T2D has not been described to date.

Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods. Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results. Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion. These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients. Cite this article: Bone Joint Res 2023;12(10):657–666

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration

There is growing interest in the peri-operative management of patients with indications for hip and knee arthroplasty in the setting of modifiable risk factors such as morbid obesity, type 2 diabetes mellitus, and smoking. A recent survey of the American Association of Hip and Knee Surgeons (AAHKS) found that 95% of respondents address modifiable risk factors prior to surgery. The aim of this study was to poll Australian arthroplasty surgeons regarding their approach to patients with modifiable risk factors. The survey tool used in the AAHKS study was adapted for use in the Australian context and distributed to the membership of the Arthroplasty Society of Australia via Survey Monkey. Seventy-seven survey responses were received, representing a response rate of 64%. The majority of respondents were experienced, high volume arthroplasty surgeons. Overall, 91% of respondents restricted access to arthroplasty for patients with modifiable risk factors. Seventy-two percent of surgeons restricted access for excessive body mass index, 85% for poor diabetic control, and 46% for smoking. Most respondents made decisions based on personal experience or literature review rather than hospital or departmental pressures. Despite differences in healthcare systems, our findings were similar to those of the AAHKS survey, although their responses were more restrictive in all domains. Differences were noted in responses concerning financial considerations for potentially underprivileged populations. The survey is currently being administered by arthroplasty societies in six other countries, allowing comparison of orthopaedic practice across different healthcare systems around the world. In conclusion, over 90% of Australian arthroplasty surgeons who responded to the survey address modifiable risk factors prior to surgery

Introduction. Diabetic foot disease is a major public health problem with an annual NHS expenditure in excess of £1 billion. Infection increases risk of major amputation fivefold. Due to the polymicrobial nature of diabetic foot infections, it is often difficult to isolate the correct organism with conventional culture techniques, to deliver appropriate narrow spectrum antibiotics. Rapid DNA-based technology using multi-channel arrays presents a quicker alternative and has previously been used effectively in intensive care and respiratory medicine. Methods. We gained institutional and Local Ethics Committee approval for a prospective cohort study of patients with clinically infected diabetic foot wounds. They all had deep tissue samples taken in clinic processed with conventional culture and real-time PCR TaqMan array. Results. 50 samples were taken from 39 patients between October 2020 and March 2022. 84% of patient were male, 88% had type 2 diabetes. The ulcers were of variable chronicity prior to sampling (range 1–113 weeks) and mean HbA1c was 67.2mmol/mol. Ulcers were on the heel (3), midfoot (6) and forefoot (41). Minimum follow up was 3 months. 6 ulcers healed, 24 patients were admitted due to foot disease, there were 2 major amputations and 4 deaths. TaqMan array results were available a mean of 4.3 days earlier than culture results. 9 patients had negative conventional cultures and 8 were negative onarray testing. 17 patients had the same organisms detected on culture and array. 16 of these 17 had additional organisms detected by array. The most frequent organisms detected on array that were not detected by culture were Staphylococcus spp., Enterobacter, Pseudomonas and fungi. Conclusion. TaqMan array shows promise in detecting infecting organisms from diabetic foot wounds and providing earlier results than standard culture, which may enable appropriate and timely antibiotic therapy

Introduction. Charcot neuroarthropathy is a debilitating condition that frequently leads to skeletal instability, and has an increased risk of ulceration leading to infection and amputation. However, surgical reconstruction may offer limb salvage and restauration of an ulcer-free, plantigrade stable foot for functional weight-bearing. We report on our case series according to a prospective protocol and analyse factors leading to a favourable outcome. Methods. We report a prospective follow-up of 62 patients undergoing Charcot reconstruction, May 2014- Jan 2022, by two surgeons. Peripheral vascular disease was routinely assessed using Duplex scan and major arterial disease was treated before reconstruction. Utilising 3D modelling, pre-operative planning and standardised osteotomies, we performed anatomical correction with radiological evidence. Definitive fixation was undertaken with internal fixation to stabilise the hindfoot. Multivariant analysis was performed to assess risk factors for failure (P>0.05 statistical significance). Results. 59 feet were included, 3 patients did not progress to definitive surgery and 3 patients had bilateral surgery. 62.7% patients were male with an average age of 56, 88.13% had Type 2 diabetes, 56% were hypertensive, 14% were on dialysis. Twenty (54.1%) single stage reconstructions had pre-operative ulceration, 3 pts had ischaemic heart disease and 36 pts had evidence of peripheral arterial disease. 81% of patients achieved normalisation of the 3 out of 4 anatomical angles (P<0.05). Two patients (3.1%) required metalwork removal for infection and limb salvage, 11 (18.6%) had delayed wound healing. Survivorship was 97% at 3yrs, and 94% at 6yrs, however if pre-existing vascular disease was present, it was 94% at 3yrs 85.3% at 6yrs. All patients were mobile at a 3 years mean follow up. Conclusion. Careful patient selection, multidisciplinary team and anatomic reconstruction led to predictable outcomes and functional limb salvage. Pre-operative vascular compromise led to a slight reduction in survivorship, but no major amputation

Abstract. Objectives. The aim of this study was to investigate whether mechanical loading induced by physical activity can reduce risk of sarcopenia in middle-aged adults. Methods. This was a longitudinal study based on a subset of UK Biobank data consisting of 1,918 participants (902 men and 1,016 women, mean age 56 years) who had no sarcopenia at baseline (assessed between 2006 and 2010). The participants were assessed again after 6 years at follow-up, and were categorized into no sarcopenia, probable sarcopenia, or sarcopenia according to the definition and algorithm developed in 2018 by European Working Group on Sarcopenia in Older People (EWGSOP). Physical activity was assessed at a time between baseline and follow-up using 7-day acceleration data obtained from wrist worn accelerometers. Raw acceleration data were then analysed to study the mechanical loading of physical activity at different intensities (i.e. very light, light, moderate-to-vigorous). Multinominal logistic regression was employed to examine the association between the incidence of sarcopenia and physical activity loading, between baseline and follow up, controlled for other factors at baseline including age, gender, BMI, smoking status, intake of alcohol, vitamin D and calcium, history of rheumatoid arthritis, osteoarthritis, secondary osteoporosis, and type 2 diabetes. Results. Among the 1918 participants with no sarcopenia at baseline, 230 (69 men and 161 women) developed probable sarcopenia and 37 (14 men and 23 women) developed sarcopenia at follow-up. Physical activity loading at moderate-to-vigorous intensity was higher in men (p<0.05), while women had higher physical activity loading at very light intensity (p<0.05). No significant difference was found in physical activity loading at light intensity between men and women (p>0.05). Logistic regression models showed that increase in physical activity loading at moderate-to-vigorous intensity significantly reduced the risk of sarcopenia (odds ratio = 0.368, p<0.05), but not probable sarcopenia (odds ratio = 0.974, p>0.05), while loading at light or very light activity intensity were not associated with the risk of sarcopenia or probable sarcopenia (p>0.05). Conclusion. Loading of physical activity at moderate-to-vigorous intensity could reduce risk of sarcopenia in middle-aged adults. 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

Osteoarthritis (OA) is the most prevalent degenerative joint disease that is a leading cause of disability worldwide. Existing therapies of OA only address the symptoms. Liraglutide is a well-known anti-diabetic medication that is used to treat type 2 diabetes and obesity. In inflammatory and post-traumatic OA animal models, liraglutide has demonstrated anti-inflammatory, pain-relieving, and cartilage-regenerating effects1 . The objective of this study is to investigate liraglutide's ability to reduce inflammation and promote anabolism in human OA chondrocytes in vitro. Pellets formed with human OA chondrocytes were cultured with a chondrogenic medium for one week to form cartilage tissue. Afterward, pellets were cultured for another 2 weeks with a chondropermissive medium. The OA group was treated with IL-1β to mimic an inflammatory OA condition. The drug group was treated with 0.5 or 10 µM liraglutide. On days 0, 1, and 14, pellets were collected. Conditioned medium was collected over the 2 weeks culture period. The gene and protein expression levels of regenerative and inflammatory biomarkers were evaluated and histological analyzes were performed. Results showed that the nitric oxide release of the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups were lower than the OA group. The DNA content of the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups were higher than the OA group on day 14. The RT-qPCR results showed that the anabolism (ACAN, COMP, and COL2) markers were higher expressed in the OA + 0.5 µM liraglutide and OA + 10 µM liraglutide groups when compared with the OA group. The inflammation (CCL-2 and IL-8) markers and catabolism markers (MMP-1, MMP-3, ADAMTS4, and ADAMTS5) had lower expression levels in the OA + liraglutide groups compared to the OA group. The histomorphometric analysis (Figure 1) supported the RT-qPCR results. The results indicate that liraglutide has anabolic and anti-inflammatory effects on human OA chondrocyte pellets. Acknowledgments: This project has received funding from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and innovation program. The funding agencies supporting this work are (in alphabetical order of participating countries): France: BPI France; Germany: Project Management Agency (DLR), which acts on behalf of the Federal Ministry of Education and Research (BMBF); The Netherlands: Netherlands Enterprise Agency (RVO); Switzerland: Innosuisse (the Swiss Innovation Agency). For any figures and tables, please contact the authors directly

The increased incidence of type 2 Diabetes Mellitus is associated with an impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin is a negative regulator of bone formation produced by osteocytes and there is recent evidence that its expression in serum is elevated in diabetic patients compared to control subjects. In this study, we test whether hyperglycemia affects serum and bone sclerostin levels in a rat model of type 2 Diabetes as well as sclerostin production by osteoblasts in culture. We used Zucker diabetic fatty (ZDF) male rats (n=6) that spontaneously develop obesity and frank diabetes around 8–9 weeks of age and Zucker lean rats as controls (n=6) to examine sclerostin expression in serum at 9, 11 and 13 weeks using a specific ELISA. Sclerostin expression in bone tibiae was examined at 12 weeks using immunocytochemistry. Rat osteoblast-like cells UMR-106 were cultured in the presence of increasing concentrations of glucose (5, 11, 22 and 44 mM) during 48 hours and sclerostin mRNA expression and release in the supernatant determined by quantitative PCR and ELISA, respectively. Our results show that serum sclerostin levels are higher in the diabetic rats compared to lean rats at 9 weeks (+ 140%, p<0.01). Our preliminary results using immunocytochemistry for sclerostin did not show any major difference in sclerostin expression in tibiae of diabetic rats compared to lean ones, although we observed many osteocytic empty lacunae in cortical bone from diabetic rats. Glucose dose-dependent stimulated sclerostin mRNA and protein production in mature UMR106 cells while it had no effect on osteocalcin expression. Altogether, our data suggest that sclerostin production by mature osteoblasts is increased by hyperglycemia in vitro and enhanced in serum of diabetic rats. Furthers studies are required to determine whether sclerostin could contribute to the deleterious effect of Diabetes on bone

Introduction and Objective. Individuals with type 2 diabetes (T2D) have a 3-fold increased risk of bone fracture compared to non-diabetics, with the majority of fractures occurring in the hip, vertebrae and wrists. However, unlike osteoporosis, in T2D, increased bone fragility is generally not accompanied by a reduction in bone mineral density (BMD). This implies that T2D is explained by poorer bone quality, whereby the intrinsic properties of the bone tissue itself are impaired, rather than bone mass. Yet, the mechanics remain unclear. The objective of this study is to (1) assess the fracture mechanics of bone at the structural and tissue level; and (2) investigate for changes in the composition of bone tissue along with measuring total fluorescent advanced glycation end products (fAGEs) from the skin, as T2D progresses with age in Zucker diabetic fatty (ZDF (fa/fa)) and lean Zucker (ZL (fa/+)) rats. Materials and Methods. Right ulnae and skin sections were harvested from ZDF (fa/fa) (T2D) and ZL (fa/+) (Control) rats at 12 and 46 weeks (wks) of age (n = 8, per strain and age) and frozen. Right ulnae were thawed for 12 hrs before micro-CT (μCT) scanning to assess the microstructure and measure BMD. After scanning, ulnae were loaded until failure via three-point bending. Fourier transform-infrared microspectroscopy (FTIR) was used to measure various bone mineral- and collagen-related parameters such as, mineral-to-matrix ratio and nonenzymatic cross-link ratio. Finally, fAGEs were measured from skin sections using fluorescence spectrometry and an absorbance assay, reported in units of ng quinine/ mg collagen. Results. At 12 and 46 wks bone size was significantly smaller in length (p < 0.01), cortical area (p < 0.001) and cross-sectional moment of inertia (p < 0.001) in T2D rats compared to age-matched controls. A slight reduction in BMD was observed in T2D rats compared to controls at both ages, however, this was not significant. Structural properties of T2D bone were significantly altered at 12 and 46 wks, with bending rigidity increasing approximately 2.5-fold and 1.5-fold in control and T2D rats with age, respectively (p < 0.0001). Similarly, yield and ultimate moment significantly reduced in T2D rats with age in comparison to controls (p < 0.0001). Energy absorbed to failure was significantly reduced in T2D rats at 46 weeks of age compared to controls (p < 0.01). The amount of energy absorbed to failure increased approximately 1.4-fold from 12 to 46 wks in control rats, however, in T2D rats a reduction was seen with age, although not significant. At 12 wks, there was no significant deficits in tissue material properties, whereas, at 46 wks a significant reduction in yield stress, yield strain and ultimate stress was observed for T2D rats in comparison to controls (p < 0.05). Conclusions. These findings show that longitudinal growth is impaired as early as 12 wks of age and by 46 wks bone size is significantly reduced in T2D rats compared to controls. The reduction in T2D structural properties is likely attributed to the bone geometry deficits. At 12 wks of age, the tissue material properties are not altered in T2D bone versus controls. However, at 46 wks, bone strength is reduced in T2D, leading to the conclusion that tissue properties are altered as the disease progresses

Introduction. Corrective fusion for the unstable deformed hind foot in Charcot Neuroarthropathy (CN) is quite challenging and is best done in tertiary centres under the supervision of multidisciplinary teams. Patients and methods. We present our results with a series of 42 hind foot deformity corrections in 40 patients from a tertiary level teaching hospital in the United Kingdom. The mean patient age was 59 (33–82). 16 patients had type1 diabetes mellitus, 20 had type 2 diabetes and 4 were non-diabetic. 18 patients had chronic ulceration. 17 patients were ASA 2 and 23 were ASA grade 3. All patients had acute single stage correction and Trigen hind foot nail fusion performed through a standard technique by the senior author and managed peri-operatively by the multidisciplinary team. Our outcome measures were limb salvage, deformity correction, ulcer healing, weight bearing in surgical shoes and return to activities of daily living (ADL). Results. At a mean follow up of 37 months (7–79) we achieved 100% limb salvage initially and 97% healing of arthrodesis. One patient with persisting non-union has been offered amputation. Deformity correction was achieved in 100% and ulcer healing in 89%. 72.5% patients are able to mobilize and manage independent ADL. There were 11 patients with one or more complications including metal failure, infection and ulcer reactivation. We performed nine repeat procedures including one revision fusion and one vascular procedure. Conclusion. Single stage corrective fusion for hind foot deformity in CN is an effective procedure when delivered by a skilled multidisciplinary team

In developed nations Charcot arthropathy is most commonly caused by diabetes mellitus. Worldwide, leprosy remains the primary cause. All evidence points to a relationship between neurologic loss, continued loading activities and the development of unrecognized bone fragmentation. In type 2 diabetes, dysregulation of leptin biology causes bone loss and may be an important factor in precipitating Charcot events. Bone density studies show massive loss of bone in patients with ankle and hindfoot Charcot problems, but not midfoot problems. This suggests a different mechanism for collapse. Stable collapse with ulcer development in the midfoot can be treated with exostectomy. Realignment and fusion remain the mainstays of treatment for diabetic Charcot neuropathy, especially in the ankle and hindfoot. Bone mineralization deficiencies require special consideration of fixation techniques. Thin wire external fixation – either as primary fixation or to reinforce/neutralize other methods can be very helpful. Large bridging screws and carefully selected bridging plates are frequently also valuable to consider. Excessive immobilization periods (often double the normal amount of time) are generally required. The goal may be limited to a braceable, plantigrade foot

Clinical evidence that patients with type 2 diabetes mellitus (T2DM) have increased risk of fractures is reported. Furthermore, thiazolidinediones, used to treat T2DM increases the risk of secondary osteoporosis & subsequent fractures. The osteogenic potency of metformin is reported in vitro, few studies have investigated the effects of metformin on bone mass and fracture healing in vivo. We aimed to investigate the effects of metformin on fracture healing in vivo. Method. 20 female Wistar rats aged 3 months were randomly divided in two groups, one group receiving saline, the other group receiving metformin administered orally via the drinking water at a concentration of 2mg/ml. After 4 weeks of metformin treatment, a mid-diaphyseal, open External fixation fracture was performed. Rats were sacrified 4 weeks later. Right contralateral tibia and left osteotomised femora were excised, bone architecture analysed by micro-CT in the right tibia. Results. No significant differences were noted between the two groups. Fracture callus volume and mineral content after 4 weeks were similar in metformin and saline groups. Discussion Our results indicate that while metformin has no adverse effects on bone, it does not promote bone mass, as suggested by in vitro studies. This confirms clinical data which have not shown direct links between metformin and decreased fracture risk

Introduction. Knee arthroplasty provides not only pain relief but also an improvement in function and range of movement. Limited joint mobility (LJM), secondary to peri-articular connective tissues stiffness, is a common complication of diabetes mellitus. We therefore examined functional outcome post-total knee arthroplasty (TKA) in a cohort of subjects with and without diabetes mellitus. Method. The effect of TKA on indices of knee function (fixed flexion, maximum flexion, total ROM and knee society score) was examined in 367 subjects with type 2 diabetes and 367 subjects without diabetes. The groups were matched for age, sex, BMI and functional movement at baseline. Participants were examined at baseline (pre-operatively), 1, 5 and 10 years post-TKA. Results. There was no significant difference in fixed flexion, maximal flexion or total range of movement between the two groups at baseline. At 1 year the group with diabetes had a significantly lower maximal flexion (p < 0.001), total range of movement (p < 0.001) and Knee Society Score (p = 0.034). At 5 years post-arthroplasty a significant increase was observed in fixed flexion (p = 0.026) as well as a significant decrease in maximal flexion (p = 0.001) and total range of movement (p = 0.004) in the diabetic group. Ten years post-arthroplasty yielded similar results. Conclusion. Within one-year post-arthroplasty people with diabetes develop a poorer range of movement compared to controls. Between one to five years post-procedure a significant fixed flexion deformity occurred in those with diabetes. A sustained deterioration was observed up to 10 years post-procedure. This study is the first to demonstrate that the pre-operative presence of diabetes mellitus leads to a worse functional outcome post-knee arthroplasty

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Context: Diabetes is associated with a several fold increase in the risk of lower extremity amputation. Although a number of epidemiologic studies have reported positive associations between glycaemia and lower extremity amputation, the magnitude of the risk has not been adequately quantified. Objective: To synthesize the available prospective epidemiologic data on the association between glycaemia as measured by glycosylated haemoglobin and lower extremity amputation in individuals with diabetes. Data Sources: We searched electronic databases (MED-LINE and EMBASE) and the reference lists of relevant articles. Study Selection: We considered prospective epidemiologic studies of cohort or nested case-control design that measured glycosylated haemoglobin level and assessed lower extremity amputation as an outcome. Of 2,398 citations identified, we included 14 studies comprising 94,640 subjects and 1,227 cases. Data Extraction: Data were abstracted using standardized forms or obtained from investigators when published information was insufficient. Data included characteristics of case and control populations, measurement of glycaemia, assay methods, outcome, and covariates. Results: The overall risk ratio for lower extremity amputation was 1.26 (95% CI, 1.16–1.36) for each percentage point increase in glycosylated hemoglobin level. There was significant heterogeneity across studies (I2: 76%, 67–86%; p< 0.001) not accounted for by recorded study characteristics. Among studies that reported the type of diabetic population, the combined estimate was 1.44 (1.25–1.65) for individuals with type 2 diabetes and 1.18 (95% CI, 1.02–1.38) for type 1 diabetes, but the difference was not statistically significant (p=0.09). We found no significant publication bias. Conclusions: There a substantial increase in risk of lower extremity amputation associated with every 1% higher HbA1c in individuals with diabetes, highlighting a potential benefit of blood glucose control. In the absence of evidence from clinical trials, this paper supports glucose-lowering as a component of overall care in the patient at high risk of amputation

Introduction: Diabetes mellitus is a systemic disease affecting peripheral nerves and the use of regional anaesthesia in diabetic patients undergoing surgery could be unpredictable. We investigated the efficacy of brachial plexus block in diabetic patients undergoing upper limb surgery compared to normal individuals. Method: Four hundred and fifty-two patients had a brachial plexus block performed under ultra-sound guidance by senior anaesthetists. There were 221 males and 231 females. Fifty-five patients were diabetic (mean age of 61 years, SD 12), 24 with type 1 and 31 with type 2 diabetes. Mean age of non-diabetic patients was 55 years (SD 15). A mixture of 0.5% Bupivacaine and 1% Prilocaine was used for the block. Post-operative proximal and distal motor and sensory functions were assessed. The assessment was conducted at a mean of 4.6 hours (SD 2.2 hours) post-operatively. MRC grading system was used to asses motor function while sensory function was assessed subjectively using a graded scale between 0, absent sensation, 1, altered sensation and 2, normal sensation. Results: Brachial plexus block was as efficient in diabetic patients proximally for motor and sensory functions compared to non-diabetic patients. There was significant difference in the efficacy of the block distally between diabetic and non-diabetic patients in both motor (P< 001) and sensory function (P< 0001). Furthermore, in diabetic patients the response to the block between type 1 and type 2 was statistically significant (P< 001). Conclusion: In diabetes, the efficacy of brachial plexus block is different compared to normal individuals. This study showed that brachial plexus block can be used efficiently in shoulder surgery in patients with diabetes. In more distal surgery, orthopaedic surgeons as well as anaesthetists should be prepared to either reinforce the block by using a local anaesthetic or to convert to general anaesthesia, if necessary, in diabetic patients