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Introduction. Infected diabetic foot is the leading cause of hospital admissions for people with diabetes mellitus. Diabetic foot osteomyelitis (DFO) causes high morbidity and significant mortality. Current diagnostic tests for DFO are either expensive, invasive, or of low diagnostic yield. Objective. The objective of the study was to determine whether serum levels of procalcitonin (PCT), an inflammatory marker, differ between DFO and diabetic foot ulcers without osteomyelitis (ie, cellulitis) as controls. The authors also aimed to assess the usefulness of PCT in diagnosing DFO. Methods. A case-control study was designed comparing DFO with diabetic foot cellulitis as the control. Patients were classified as having osteomyelitis and cellulitis based on the International Working Group on the Diabetic Foot diagnostic criteria. Serum inflammatory markers PCT, adiponectin, C-reactive protein-1, osteoprotegerin (OPG), osteopontin (OPN), and interleukin 6 (IL-6) were analyzed in patients with DFO and controls. Results. The median serum procalcitonin was significantly higher in the DFO group 108.5 pg/mL (range, 65.0–124.0 pg/mL) compared with 57.0 pg/mL (range, 37.2–77.0 pg/mL) controls (P = .02). Procalcitonin had a sensitivity of 79% compared with 50%, 63%, 66%, and 75% for adiponectin, OPG, OPN, and IL-6, respectively. Procalcitonin had a specificity of 70% compared with 50%, 71%, 70%, and 64%. Receiver operator characteristic curves showed a value of area under the curve of 0.73 and 0.77 for PCT and IL-6 compared with 0.4, 0.6, and 0.6 for adiponectin, OPG, and OPN, respectively. Conclusions. In this study, procalcitonin was a useful diagnostic test for DFOs and provided distinct diagnostic discrimination between DFO from cellulitis. It may serve as a useful marker for diagnosing DFO. Further studies in a larger population are needed to verify the findings.

Background and Aims: Nerve conduction study (NCS) measures how fast an electrical impulse moves through the nerve and is a standard technique for diagnosing and assessing neurological diseases. Despite diabetes and obesity being a common accompaniment of peripheral neuropathy, their effects on NCS patterns have not been elucidated conclusively. Our study aimed to assess several anthropometric and metabolic factors with NCS outcomes to address this gap. Research Design and Methods: This retrospective chart analysis study was conducted on subjects who underwent NCS between 1 January 2009 and 31 December 2019 at a regional hospital. Metabolic, anthropometric, demographical and NCS data were collected from patients’ health records. Results: In total, 120 subjects presenting with sensorimotor peripheral neuropathy symptoms were included in the study. Age, HbA1c, urea and ESR variables were significantly negatively associated with nerve conduction outcomes (Spearman’s correlation rho between −0.210 and −0.456, p &lt, 0.038). HbA1c and age consistently had the most substantial contribution to velocity and amplitude in all regression models (beta coefficients between −0.157 and 0.516, p &lt, 0.001). Urea also significantly account for a large amount of variance in amplitude and velocity in the lower limbs. Conclusion: This study suggests that the severity of sensorimotor neuropathy is influenced by glycaemic control, age and uraemia. The interpretation of NCS results must consider these factors suggesting that improved glycaemic and uraemic control may improve nerve conduction outcomes.

Background Diabetes foot ulcer (DFU) is a complication of diabetes mellitus. Accurate diagnosis of DFU severity through inflammatory markers will assist in reducing impact on quality of life. We aimed to ascertain the diagnostic test accuracy of commonly used inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and white cell count (WCC) for the diagnosis and differentiation between DFU grades based on the International Working Group on the Diabetic Foot classification system. Methods This systematic review explored studies that investigated one or more of the above-listed index tests aiding in diagnosing infected DFU. This review was registered on PROSPERO database (ID = CRD42021255618) and searched 5 databases including an assessment of the references of included studies. Records were manually screened as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A total of 16 studies were included which were assessed for quality using QUADAS-2 tool and meta-analysed using Meta-Disc v1.4. Results CRP had the greatest area under the curve (AUC) of 0.893 for diagnosing grade 2 DFU. This returned a pooled sensitivity and specificity of 77.4% (95% CI: 72% to 82%) and 84.3% (95% CI: 79% to 89%) respectively. In terms of diagnosing grade 3 DFU, procalcitonin had the highest AUC value of 0.844 when compared with other markers. The pooled sensitivity of PCT was calculated as 85.5% (95% CI: 79% to 90%) and specificity as 68.9% (95% CI: 63% to 75%). Conclusion CRP and PCT are the best markers for diagnosing grade 2 and grade 3 DFU respectively. Other markers are also valuable when used in conjunction with clinical judgement. The findings accentuate the necessity of further research to establish standardised cut-off values for these inflammatory markers in diagnosing diabetic foot ulcers.

Background: Mobile applications (apps) have proven to be useful in supporting diabetes self-care, but non-consideration of users’ needs and non-inclusion of educational features are reasons for low continual use. Well-designed mobile apps that meet the needs of diabetes patients and provide ongoing self-management education and support are required. It was hypothesized that apps designed with such features can improve a range of measures including clinical outcomes, knowledge of diabetes, medication adherence, perceived ability for self-management, and quality-of-life. This may eventually facilitate a more robust and cost-effective approach for improving skills and motivation for the management of diabetes. Methods: This project will be conducted in two phases. It will initially employ a mixed methods study design to investigate the self-management needs and perceptions of diabetes patients on the use of mobile apps to support diabetes self-management. Results of the mixed methods study will inform the content and design of an app which will be employed as an intervention tool in a 12-month parallel randomized controlled trial (RCT). The RCT will compare outcomes in relation to standard-of-care alone with standard-of-care plus a mobile phone diabetes app among 150 insulin-requiring types 1 and 2 diabetes patients. The primary outcome measures are clinical parameters such as hemoglobin A1c (HbA1c), lipids, urine albumin-to-creatinine ratio, blood pressure, frequency in events of emergency hyperglycemia and hypoglycemia. Secondary outcomes include knowledge of diabetes, medication intake and adherence, perception of self-care, and quality-of-life. Discussion: Results from this study will provide empirical evidence on the usefulness of a mobile app developed based on self-management needs analysis of diabetic patients. The long-term goal is to harness knowledge gained from this study to provide evidenced-based data, which promote the scale-up or adoption of mobile applications that provide regular, ongoing education and self-management support to people living with diabetes. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000065291, Registered on 17 January, 2018 (prospectively registered)., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://www.youtube.com/watch?v=tGt_fYIKA9I

The study aimed at determining prevalence and risk factors (RFs) of diabetic lower limb amputations (LLAs).Electronic databases including PubMed, Medline, Web of Science, and Cochrane Library were searched from January 2003 to April 2021.Sixteen full-text published studies were reviewed. The prevalence of LLAs stood as high as 66%, with a combined prevalence of 19% (95% CI 10-29) using the random-effects model. The most prominent RFs for LLA were duration of diabetes mellitus (DM), age, renal impairment, and ethnic minority. Amongst Australians, Indigenous background is strongly associated with increased risk of the diabetic foot (DF) LLA.LLAs are considerably prevalent amongst patients with the DF and occur at even higher rates in patients with multimorbidity.

Background: Diabetes mellitus causes a large majority of non-traumatic major and minor amputations globally. Patients with diabetes are clinically complex with a multifactorial association between diabetic foot ulcers (DFU) and subsequent lower extremity amputations (LEA). Few studies show the long-term outcomes within the cohort of DFU-associated LEA. Aim: To highlight the long-term outcomes of LEA as a result of DFU. Methods: PubMed/MEDLINE and Google Scholar were searched for key terms, "diabetes", "foot ulcers", "amputations" and "outcomes". Outcomes such as mortality, re-amputation, re-ulceration and functional impact were recorded. Peer-reviewed studies with adult patients who had DFU, subsequent amputation and follow up of at least 1 year were included. Non-English language articles or studies involving children were excluded. Results: A total of 22 publications with a total of 2334 patients were selected against the inclusion criteria for review. The weighted mean of re-amputation was 20.14%, 29.63% and 45.72% at 1, 3 and 5 years respectively. The weighted mean of mortality at 1, 3 and 5 years were 13.62%, 30.25% and 50.55% respectively with significantly higher rates associated with major amputation, re-amputation and ischemic cardiomyopathy. Conclusion: Previous LEA, level of the LEA and patient comorbidities were significant risk factors contributing to re-ulceration, re-amputation, mortality and depreciated functional status.

There is limited literature on IHD in DFU patients. This review aimed to determine the prevalence of and risk factors of IHD in patients with DFUs.Seven electronic databases were searched from inception to April 2021.The prevalence of IHD in DFU patients ranged from 6.83% to 60.61% with a pooled mean of 25.85% (95% CI, 24.28%-27.32%). Several risk factors were identified including hypertension, male gender, smoking, and peripheral vascular disease.We identified multiple risk factors for IHD requiring early interventions to increase long-term quality of life for patients with DFUs.

Background:Both activation of monocytes and increased serum fatty acid binding protein-4 (FABP4) occur in diabetes and are associated with increased atherosclerosis. The oxidized lipid, 9-hydroxyoctadecadienoic acid (9-HODE) increases FABP4 in macrophages, and is a ligand for G protein-coupled receptor 132 (GPR132). We investigated the involvement of GPR132 in mediating the 9-, 13-HODE stimulation of FABP4 secretion, and whether GPR132 expression is increased in monocytes from patients with type 2 diabetes.Methods:The effects of siRNA silencing of GPR132 gene and of the PPAR-γ antagonist T0070907 were studied in THP-1 cells. Serum levels of FABP4 and other adipokines were measured in patients with diabetes, and monocyte subpopulations were analyzed using flow cytometry. GPR132 mRNA was quantified in isolated CD14+cells.Results:9-HODE and 13-HODE increased FABP4 expression in THP-1 monocytes and macrophages, and also increased GPR132 expression. Silencing of GPR132 did not influence the increase in FABP4 with 9-HODE, 13-HODE, or rosiglitazone (ROSI). By contrast, T0070907 inhibited the effect of all three ligands on FABP4 expression. Diabetic subjects had increased serum FABP4, and activated monocytes. They also expressed higher levels of GPR132 mRNA in CD14+cells.Conclusions:We conclude that GPR132 is an independent monocyte activation marker in diabetes, but does not contribute to PPAR-γ-mediated induction of FABP4 by HODEs.

Asia-Pacific countries are experiencing lifestyle-related non-communicable disease crises. Kimbe, one of Papua New Guinea’s provincial capitals is noted as the fastest growing city in the South Pacific subcontinent yet its impact on diabetes mellitus (DM) is not known. To determine pattern of newly diagnosed DM, we conducted a retrospective review of Kimbe General Hospital medical admissions from January 2009 to December 2012. 125 patients were diagnosed with diabetes with male: female ratio of 1.1: 1. Overall, number of patients diagnosed with DM at the hospital increased rapidly from 16 in 2009 to 49 in 2012; p

Aims To evaluate outcomes of diabetic inpatient hypoglycemia among Aboriginal and Torres Strait Islander (ATSI) compared with Australian Caucasian patients. Methods A retrospective audit of diabetic patients aged > 18 years admitted at a regional hospital general ward between April 1, 2015, and March 31, 2016, was analyzed. The database contains clinical information at the time of admission and initial discharge and readmission within 4 weeks thereafter. Results A total of 1618 (of 6027) patients were admitted with diabetes representing 23.7% of the total ward admissions, of which 484 (29.9%) had inpatient hypoglycemia. Of the 91 patients with available data analyzed, ATSI origin with inpatient hypoglycemia was associated with longer length of stay (LOS) (hazard ratio [HR], 2.1, 95% confidence interval [CI], 1.2-3.5), whereas severe hypoglycemia (≤ 2.2 mmol/L) in both ATSI and non-ATSI was significantly associated with longer LOS (HR, 2.3; 95% CI, 1.2-4.2). No significant differences in LOS were found for gender, age, and Carlson comorbidity index (CCI). The adjusted model for likelihood of readmission, gender, indigenous status, and CCI were not significant risk factors for readmission to the hospital. Readmitted patients were older (50-59 years vs Conclusion We reported high rate of inpatient hypoglycemia in our study population. Indigenous Australian diabetic patients with inpatient hypoglycemia had significantly longer LOS compared with non-Indigenous Caucasian counterparts. Further prospective studies on a larger population are needed to confirm our findings.

Background: The prevalence of diabetes in rural and remote North Queensland is twice that of the general Australian population. The vast geographical distances in North Queensland prevent patients from accessing specialist diabetes care in tertiary hospitals. Telehealth (TH) presents a unique opportunity to overcome this barrier. However, the ability of TH to improve glycaemic control and vascular risk factors (blood pressure, body mass index, lipid profile) in comparison to traditional face-to-face (FTF) care in this population remains unknown. Methods: This was a retrospective cohort study of all diabetes-related telehealth consultations conducted at the Townsville Hospital from January 2016 to March 2018. The primary outcome was the change in HbA1c post-FTF (face-to-face) care versus post-TH care. Secondary outcomes included change in blood pressure, body mass index and lipid profile. We conducted a preliminary economic analysis to determine patient cost-savings from the tele-diabetes model of care. Results: 330 patients were included in the study. The majority (71%) had a diagnosis of type 2 diabetes. The median baseline HbA1c was 9.1% (8.0-10.8). HbA1c improved from 9.1% (post-FTF) to 8.1% post-TH intervention (z = -9.184, p Conclusions: Telehealth consultations improved glycaemic control and lipid levels more effectively than traditional face-to-face care with significant cost savings for a rural and remote population in North Queensland, Australia. Disclosure N. Nangrani: None. U. Malabu: None. V. Vangaveti: None.

Objective Dipeptidyl peptidase-4 (DPP-4) inhibitors have a well-known effect on glycaemic control in patients with diabetes but little is known on their wound healing role in this group of population. This paper reviews the effects of DPP-4 inhibitors on wound healing of diabetic foot ulcers. Methods Published data on effects and mechanism of DDP-4 inhibitors on wound healing were derived from Medline, PubMed and Google Scholar search of English language literature from 1994 to 2014 using the key words such as “DPP-4 inhibitors”, “endothelial healing” “diabetes” and “chronic ulcers”. Results DPP-4 inhibitors show a potential benefit in processes of wound healing in diabetic chronic foot ulcers. The enzyme inhibitors promote recruitment of endothelial progenitor cells and allow the final scaffolding of wounds. Furthermore DPP-4 inhibitors augment angiogenesis and have widespread effects on optimising the immune response to persistent hypoxia in chronic diabetes wounds. Conclusion DPP-4 inhibitors show promise in the local wound healing of diabetic foot ulcers in addition to its already established glycaemic control. In the light of high rate of amputations due to non-healing ulcers with profound psychological and economical liability, more investigations on the usefulness of DPP-4 inhibitors in the high risk diabetes population are needed.

ObjectiveThe study aimed to identify the common gaps in skills and self-efficacy for diabetes self-management and explore other factors which serve as enablers of, and barriers to, achieving optimal diabetes self-management. The information gathered could provide health professionals with valuable insights to achieving better health outcomes with self-management education and support for diabetes patients.MethodsInternational online survey and telephone interviews were conducted on adults who have type 1 or type 2 diabetes. The survey inquired about their skills and self-efficacy in diabetes self-management, while the interviews assessed other enablers of, and barriers to, diabetes self-management. Surveys were analysed using descriptive and inferential statistics. Interviews were analysed using inductive thematic analysis.ResultsSurvey participants (N = 217) had type 1 diabetes (38.2%) or type 2 diabetes (61.8%), with a mean age of 44.56 SD 11.51 and were from 4 continents (Europe, Australia, Asia, America). Identified gaps in diabetes self-management skills included the ability to: recognize and manage the impact of stress on diabetes, exercise planning to avoid hypoglycemia and interpreting blood glucose pattern levels. Self-efficacy for healthy coping with stress and adjusting medications or food intake to reach ideal blood glucose levels were minimal. Sixteen participants were interviewed. Common enablers of diabetes self-management included: (i) the will to prevent the development of diabetes complications and (ii) the use of technological devices. Issues regarding: (i) frustration due to dynamic and chronic nature of diabetes (ii) financial constraints (iii) unrealistic expectations and (iv) work and environment-related factors limited patients' effective self-management of diabetes.ConclusionsEducational reinforcement using technological devices such as mobile application has been highlighted as an enabler of diabetes self-management and it could be employed as an intervention to alleviate identified gaps in diabetes self-management. Furthermore, improved approaches that address financial burden, work and environment-related factors as well as diabetes distress are essential for enhancing diabetes self-management.

BackgroundMobile phone applications (apps) offer motivation and support for self-management of diabetes mellitus (DM), but their use is limited by high attrition due to insufficient consideration of end-users perspectives and usability requirements. This study aimed to examine app usage and feature preferences among people with DM, and explore their recommendations for future inclusions to foster engagement with diabetes apps.MethodsThe study was conducted internationally on adults with type 1 or type 2 DM using online questionnaire (quantitative) to investigate usage and preferences for app features that support diabetes self-management and semi structured telephone interview (qualitative) to explore suggestions on fostering engagement and specific educational information for inclusion into diabetes apps. Survey and interview data were analysed using descriptive/ inferential statistics and inductive thematic analysis respectively.ResultsA total of 217 respondents with type 1 DM (38.25%) or type 2 DM (61.8%), from 4 continents (Australia, Europe, Asia and America) participated in the survey. About half of the respondents (48%) use apps, mainly with features for tracking blood glucose (56.6%), blood pressure (51.9%) and food calories (48.1%). Preferred features in future apps include nutrient values of foods (56.7%), blood glucose (54.8%), physical exercise tracker (47%), health data analytics (42.9%) and education on diabetes self-management (40.6%). Irrespective of the type of DM, participants proposed future apps that are user friendly, support healthy eating, provide actionable reminders and consolidate data across peripheral health devices. Participants with type 1 DM recommended customised features with news update on developments in the field of diabetes. Nominated specific educational topics included tips on problem solving, use of insulin pump therapy, signs of diabetes complication and transitioning from paediatric into adult care.ConclusionsThe study has highlighted patients' perspectives on essential components for inclusion in diabetes apps to promote engagement and foster better health outcomes.

[Extract] The observations by Bakhtiyari and Mansournia on our study [1] were received with great interest. We believe our study was consistent with a case-control format [2]. In particular, our target population was selected from subjects diagnosed with diabetic foot ulcer (DFU) at the local high-risk foot clinic, effectively fulfilling the criteria of control (DFU without amputations) and case (DFU with amputation), as previously described [3].

A hypoglycemia-induced fall is common in older persons with diabetes. The etiology of falls in this population is usually multifactorial, and includes microvascular and macrovascular complications and age-related comorbidities, with hypoglycemia being one of the major precipitating causes. In this review, we systematically searched the literature that was available up to March 31, 2014 from MEDLINE/PubMed, Embase, and Google Scholar using the following terms: hypoglycemia; insulin; diabetic complications; and falls in elderly. Hypoglycemia, defined as blood glucose, Video abstract

Objective: To look into the glucose tolerance test characteristics and determine complications in non-gestational diabetes pregnant subjects. Methods: From 2006 to 2009 all non-gestational diabetes mellitus (non-GDM) pregnant women who delivered macrosomia at the North Australia's Townsville Hospital were retrospectively reviewed by extracting data from clinical record. Glucose tolerance tests results were analysed in the light of an earlier diagnosis of non-GDM. Results: Ninety-one non-GDM mothers with macrosomia were studied and compared with 41 normoglycemic subjects without macrosomia. Of the subjects with non-GDM macrosomia, 45 (49.4%) had normal 50 g glucose challenge test (GCT) without further testing, another 8 (8.8%) had abnormal GCT but normal 75 g oral glucose tolerance test (OGTT). A total of 4 (4.4%) subjects had normal GCT and OGTT. Interestingly, 14 out of 16 (87.5%) subjects who were tested with OGTT owing to past history of macrosomia had normal results but delivered macrosomic babies. Only 12 subjects had both GCT and OGTT, the rest of the cohort had either of the two tests. Subjects with non-GDM macrosomia had higher frequency of neonatal hypoglycaemia 34% as compared to 10% in non-macrosomic babies (P=0.003). Other feto-maternal complications were similar in both groups. Conclusions: No significant pattern of glucose tolerance characteristics was identified in non-GDM mothers with macrosomic babies. In spite of being normoglycemic significant neonatal hypoglycaemia was recorded in non-GDM macrosomic babies. Further prospective studies on a larger population are needed to verify our findings.

Objective.The aim of the study was to evaluate the prevalence of and risk factors for lower limb amputation in a specialist foot clinic-based setting.Methods.A retrospective quantitative study was conducted, using clinical and biochemical profiles of diabetic foot patients attending the High Risk Foot Clinic at The Townsville Hospital, Australia, between January 1, 2011, and December 31, 2013.Results.The total study sample included 129 subjects, comprising 81 males and 48 females with M : F ratio of 1.7 : 1. Twenty-three subjects were Indigenous Australians, representing 17.8% of the study population. The average age of the cohort was 63.4 years ± 14.1 years [CI 90.98–65.89]. Lower limb amputation was identified as a common and significant outcome (n=44), occurring in 34.1%, more commonly amongst the Indigenous Australians (56.5% versus 29.2%;p=0.94, OR 0.94). Risk factors most closely associated with amputation included diabetic retinopathy (p=0.00, OR 4.4), coronary artery bypass graft (CABG) surgery (p=0.01, OR 4.1), Charcot’s arthropathy (p=0.01, OR 2.9), and Indigenous ethnicity (p=0.01, OR 3.4). Although average serum creatinine, corrected calcium, and glycosylated haemoglobin A1c (Hba1c) levels were higher amongst amputees they were statistically insignificant.Conclusions.Lower limb amputation is a common outcome and linked to ethnicity and neurovascular diabetic complications amongst subjects with diabetic foot ulcer. Further research is needed to identify why risk of lower limb amputation seems to differ according to ethnicity.

End-stage renal failure (ESRF) and dialysis have been identified as a risk factor for lower limb amputations (LLAs). High rate of ESRF amongst the Australian population has been reported, however till date no study has been published identifying magnitude and risk factors of LLA in subjects on renal dialysis.The study aims to document trends in the prevalence and identify risk factors of non-traumatic LLA in Australian patients on dialysis.A retrospective review of all patients (218) who attended the regional dialysis center between 1st January 2009 and 31st December 2013 was conducted. Demographic, clinical and biochemical data were analyzed.We identified a high prevalence of 13.3% of LLAs amongst Australian patients with ESRF on dialysis at our center. The associated risk factors were the presence of diabetes (OR 1.67 [1.49-1.88] p 0.001), history of foot ulceration (OR 81 [18.20-360.48] p 0.001), peripheral arterial disease (OR 31.29 [9.02-108.56] p 0.001), peripheral neuropathy (OR 31.29 [9.02-108.56] p 0.001), foot deformity (OR 23.62 [5.82-95.93] p 0.001), retinopathy (OR 6.08 [2.64-14.02] p 0.001), dyslipidemia (OR 4.6 [1.05-20.05] p= 0.049) and indigenous background (OR 3.39 [1.38-8.33] p= 0.01). 75% of the amputees had aboriginal heritage. We also identified higher HbA1c and CRP levels as well as low serum albumin, hemoglobin and vitamin D levels to have a strong association with LLAs (p 0.05).There is high prevalence of LLAs amongst Australian indigenous patients with diabetes on dialysis in North Queensland. Other strongly associated risk factors include history of foot ulceration, foot deformity and peripheral neuropathy as well as high HbA1c levels and low serum albumin levels.

Background.Renal dialysis has recently been recognised as a risk factor for lower limb amputation (LLA). However, exact rates and associated risk factors for the LLA are incompletely understood.Aim.Prevalence and risk factors of LLA in end-stage renal failure (ESRF) subjects on renal dialysis were investigated from the existing literature.Methods.Published data on the subject were derived from MEDLINE, PubMed, and Google Scholar search of English language literature from January 1, 1980, to July 31, 2015, using designated key words.Results.Seventy studies were identified out of which 6 full-text published studies were included in this systematic review of which 5 included patients on haemodialysis alone and one included patients on both haemodialysis and peritoneal dialysis. The reported findings on prevalence of amputation in the renal failure on dialysis cohort ranged from 1.7% to 13.4%. Five out of the six studies identified diabetes as the leading risk factor for amputation in subjects with ESRF on renal dialysis. Other risk factors identified were high haemoglobin A1c, elevated c-reactive protein, and low serum albumin.Conclusions.This review demonstrates high rate of LLA in ESRF patients receiving dialysis therapy. It has also identified diabetes and markers of inflammation as risk factors of amputation in ESRF subjects on dialysis.

Diabetic Foot Ulcers (DFUs) are major complications associated with diabetes and often correlate with peripheral neuropathy, trauma and peripheral vascular disease. It is necessary to understand the molecular and genetic basis of diabetic foot ulcers in order to tailor patient centred care towards particular patient groups. This review aimed to evaluate whether current literature was indicative of an underlying molecular and genetic basis for DFUs and to discuss clinical applications. From a molecular perspective, wound healing is a process that transpires following breach of the skin barrier and is usually mediated by growth factors and cytokines released by specialised cells activated by the immune response, including fibroblasts, endothelial cells, phagocytes, platelets and keratinocytes. Growth factors and cytokines are fundamental in the organisation of the molecular processes involved in making cutaneous wound healing possible. There is a significant role for single nucleotide polymorphism (SNPs) in the fluctuation of these growth factors and cytokines in DFUs. Furthermore, recent evidence suggests a key role for epigenetic mechanisms such as DNA methylation from long standing hyperglycemia and non-coding RNAs in the complex interplay between genes and the environment. Genetic factors and ethnicity can also play a significant role in the development of diabetic neuropathy leading to DFUs. Clinically, interventions which have improved outcomes for people with DFUs or those at risk of DFUs include some systemic therapeutic drug interventions which improve microvascular blood flow, surgical interventions, human growth factors, and hyperbaric oxygen therapy, negative pressure wound therapy, skin replacement or shockwave therapy and the use of topical treatments. Future treatment modalities including stem cell and gene therapies are promising in the therapeutic approach to prevent the progression of chronic diabetic complications.

Background Dipeptidyl peptidase-4 (DPP-4) inhibitors are a relatively new class of anti-diabetic drugs that have therapeutic potential in the management of atherosclerosis. Of the numerous DPP-4 inhibitors in clinical practice no studies have been conducted to compare their anti-atherosclerotic effects despite growing evidence of their usefulness in the high risk population. Objective The aim of the study was to review the anti-athero-thrombotic effects of DPP-4 inhibitors in atherosclerotic diseases. Method A literature search was conducted on MEDLINE and the COCHRANE Library using the terms “DPP-4 Inhibitors”, “atherosclerosis”, “GLP”, “inflammation”, “cytokines”, “stroke”, “ischaemic heart disease”, “hypertension” and “peripheral vascular disease”. A mathematical model devised by us was used to derive and compare the anti-inflammatory effects of the DPP-4 inhibitors using protective score [PS]. Data was analysed for alogliptin, linagliptin, saxagliptin, sitagliptin, and vildagliptin. Results Sixty two published studies collected in the search were assessed for relevance to this study. Sitagliptin had the highest PS [ n = 5] while linagliptin and saxagliptin yielded the lowest PS [ n = 1]. This comparison and scoring system was limited to the data collected; which did not investigate for all athero-thrombotic factors selected in this study. Conclusion The findings suggest potential usefulness of DPP-4 in atherosclerotic diseases. It also reflected a possible superiority of sitagliptin over the other DPP-4 inhibitors in the management of atherosclerosis. Further investigations are required to establish specific inflammatory cytokines influenced by the DPP-4 inhibitors and to elucidate their clinical application in athero-thrombotic disease.

Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia.

We analysed the clinical outcomes of using a standardised protocol in the management of diabetic ketoacidosis. Of 71 admissions, the protocol group (n = 35) had significantly shorter length of hospitalisation, shorter time to normalise bicarbonate, fewer incidence of hypokalaemia and hypoglycaemia compared with the control group (n = 36).

Neuropeptide Y (NPY), a thirty-six amino acid peptide, is a potent centrally-acting appetite-stimulating agent which is believed to regulate eating behaviour and body weight (Williams et al. 1991). Lactation in rodents is associated with increased nutrient requirements which are met by extraordinary increases in food intake (Vernon, 1989). The aim of the present study was to investigate whether hyperphagia in lactating rats is associated with increased hypothalamic NPY levels, as in the case of other hyperphagic states such as starvation and diabetes. Twenty female Wistar rats, initially matched for age and weight, were studied. The experiment began when the lactating group (n 10) was on average at day 16 of lactation (range, 13-17). The lactating rats’ food intake was over 330% that of the controls (P 0.05). Four of the eight hypothalamic areas showed significantly increased NPY levels in the lactating rats compared with controls, namely: the arcuate nucleus-median eminence (+41%; P

Vanadate mimics insulin action in vitro, lowers blood glucose in diabetic rats, and has been suggested as a novel treatment for diabetes. However, it also inhibits feeding which itself could lower blood glucose. We assessed the contribution of hypophagia to vanadate's anti-hyperglycaemic action in a 3-week study of streptozotocin-diabetic (STZ-DM) rats. Untreated diabetics (n =8) ate significantly more than non-diabetic controls (n=8; food intake, 68±3 (SEM) vs 44±1 g rat⁻¹ day⁻¹, p 0.05). The glucose-lowering effect of vanadate in STZ-DM rats is therefore due entirely to its suppression of feeding. It may have no specific anti-diabetic action in vivo.

NPY, a major hypothalamic peptide, stimulates feeding, insulin secretion and weight gain when injected intrahypothalamically. NPY synthesis in the arcuate nucleus (ARC) and levels in NPY-sensitive hypothalamic regions rise in diabetes and starvation, possibly stimulated by insulin deficiency. High pharmacological intracerebroventricular insulin levels inhibit NPY synthesis in the ARC, but the effects of hyperinsulinaemia have not been studied. We therefore measured regional hypothalamic NPY levels in rats during a hyperinsulinaemic, euglycaemic clamps. Male Wistar rats with implanted jugular cannulae, fasted for 24 hrs, were infused with insulin (128.2 mU1⁻¹ at 780 μl hr⁻¹ (n = 7) together with variable-rate glucose to maintain euglycaemia (3.9± 0.1 mmoll⁻¹), or saline (n=8; glycaemia, 4.0±0.5 mmoll⁻¹), for 2.5 hrs. Insulin levels were 80.2±10.4 mUl⁻¹ in insulin-infused rats and 16.7±11.7 mUl⁻¹ in saline-treated controls (p

[Extract] Waters et al. (1) discuss further evidence relating to increased incidence of new diabetes with statins. Superficially, the message from these and other studies is reassuring: statins have transformed the management of atherosclerotic disease; intensive therapy shows greater benefit than "standard" therapy; the rate of incident diabetes with statins is relatively small; benefits of statins are still apparent in patients with diabetes. It is further reassuring from this study (using data from the TNT [Treating to New Targets] and IDEAL [Incremental Decrease in Endpoints through Aggressive Lipid-lowering] studies) that those who develop diabetes are those who appear to be at risk.

Vanadate treatment can lower glycemia in diabetic rats. This action is generally attributed to vanadate's insulinomimetic properties, but vanadate also inhibits feeding, which could lower blood glucose. We therefore assessed the contribution of hypophagia to vanadate's antihyperglycemic action in a 3-week study of streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54% more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had significantly lower food intakes (P < 0.001) than untreated diabetic rats. In vanadate-treated diabetic rats, blood glucose levels were significantly lower than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats). Vanadate treatment did not affect plasma insulin concentrations in diabetic rats. In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without significantly affecting glycemia. To investigate the mechanism of vanadate's hypophagic effect, we also measured regional hypothalamic levels of neuropeptide Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in diabetes and are normalized by insulin replacement. Unlike insulin, vanadate treatment did not normalize regional hypothalamic NPY concentrations in diabetic rats. Vanadate does not therefore appear to exert an insulin-like action at the hypothalamic level; its hypophagic action does not appear to involve inhibition of NPYergic pathways in the hypothalamus. We conclude that the glucose-lowering effect of vanadate in STZ-induced diabetic rats can be explained by its inhibition of feeding. Although vanadate has certain insulinomimetic effects in vitro and in vivo, the role of these effects in vanadate's antidiabetic actions must be critically reexamined.

D-Fen, a widely used anorectic drug, is reported to improve insulin sensitivity and glycaemic control in human non-insulin dependent diabetes independently of its anorectic effect. A dose renge of 0.5, 1.0, 2.5, 5.0 mg/kg of D-fen was given by gavage to male Wistar rats (n=10) that had been made diabetic by streptozotocin (55 mg/kg) for 3 weeks. The untreated diabetic group and nondiabetic group received water by gavage. After 24 h food deprivation, glucose (1 g/kg) was given by gavage to all 3 groups, 2 hours after D-fen or water treatment and 15-minute tail-prick blood samples (5ul) were collected for 2 h to assess the effects of D-fen on glucose tolerance. D-fen significantly reduced glucose levels only at the 5 mg/kg dose during the 2 hours before and during the glucose tolerance test compared with the untreated diabetic and non-diabetic groups, peak delta glucose (D-fen 0.23±0.2 mnol/l vs untreated diabetic 5.2±1.2,p