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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: 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

Summary Whilst literature is expanding on pasireotide use in the management of Cushing’s disease (CD), there is still currently much unknown about long-term and low-dose pasireotide use in CD. We present a 60-year-old female with residual CD after transphenoidal surgery (TSS), being successfully managed with S.C. pasireotide for over 10 years. For 6 years, her S.C. pasireotide was inadvertently administered at 360 µg twice daily (BID), almost half the recommended dose of 600 µg BID. Despite the low-dose, her urinary free cortisol (UFC) normalised within 6 months and Cushingoid features resolved. She remained in biochemical and clinical remission on the same low-dose for 6 years, before a medication audit discovered her mistaken dose and directed her to take 600 µg BID. With the higher dose 600 µg BID for the next 5 years, her glycaemia worsened without any changes in her UFC and residual tumour volume. Our case showed the continuing effectiveness and safety of treatment with S.C. pasireotide for more than 10 years, and that a low-dose regimen may be considered an option for responders by its safety profile. Learning points: A lower dose of pasireotide may be effective in the initial treatment of CD than the recommended 600 µg BID dosage, though more studies are required to explore this. Low-dose pasireotide use has the benefit of minimising adverse effects. In the long-term, pasireotide has a sustained clinical and biochemical effect and is well tolerated.

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.

The aim of this study was to evaluate the preliminary efficacy and user acceptance of My Care Hub (MCH) mobile app&mdash, developed to provide evidenced-based support and education on diabetes self-management (DSM). Using a mixed-methods design, the efficacy and acceptability of MCH were measured among people with type 1 or type 2 diabetes after three weeks of intervention. The primary outcome measure was level of involvement with DSM, while the mediating factors were skills and self-efficacy for DSM. Telephone interviews were conducted to elucidate information on perceptions of the app&rsquo, s impact on participants&rsquo, DSM and interest in future use. Statistically significant improvements were observed between pre- and post-intervention measures: DSM activities (4.55 &plusmn, 1.14 vs. 5.35 &plusmn, 0.84, p = 0.001), skills (7.10 &plusmn, 1.99 vs. 7.90 &plusmn, 1.67, p = 0.04), and self-efficacy (7.33 &plusmn, 1.83 vs. 8.07 &plusmn, 1.54, p = 0.03). Multivariate analysis showed that self-efficacy had the strongest, though not significant influence on DSM. Interview findings revealed that the app reinforced knowledge and provided motivation to participate in DSM activities. The study suggested a positive impact of MCH on DSM and acceptability by patients. To confirm these promising results, further large scale and long-term studies are required.

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

Aneurysms demonstrate vascular smooth muscle cells (VSMC) phenotypic modulation characterized by the prevailing of synthetic over contractile properties. We have shown previously the ability of interferon-gamma (IFN-γ) to switch VSMC from contractile to synthetic phenotype via upregulating the truncated form of tryptophanyl-tRNA synthetase (mini-TrpRS) in vitro. Here we discuss a possible role of the IFN-γ/mini-TrpRS signalling axis in the pathology of human abdominal aortic aneurysm (AAA).

Diabetic foot syndrome demonstrates wound chronicity due to impaired tissue perfusion in lower limbs. Previous studies showed interferon-gamma (IFN-γ), a central inflammatory mediator in diabetic foot syndrome, to induce the truncated form of tryptophanyl-tRNA synthetase (mini-TrpRS) that has strong angiostatic properties. Recently we reported that mini-TrpRS signalling could be blocked in the presence of IFN-γ with D-tryptophan in vitro. Here we discuss the IFN-γ/mini-TrpRS axis in the pathology of diabetic foot syndrome and emerging therapeutic options.

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.

Sodium-glucose cotransporter type-2 inhibitors (SGLT2is) reduce glomerular hyperfiltration in diabetic people with early diabetic nephropathy. The objective of this report was to assess changes in glomerular filtration rate in healthy cats after treatment with a SGLT2i. Eight healthy research adult castrated male cats were used in a randomized, controlled, cross-over study design. We induced isolated renal tubular glucosuria by dosing cats with the SGLT2i dapagliflozin. The cats received by mouth 10 mg dapagliflozin or control every 24 h in each of the 4, 5-d trial periods that were separated by a 7-d washout period. We assessed glomerular filtration rate (iohexol clearance method), serum urea, creatinine, symmetric dimethylarginine, and 24-h sodium and chloride urinary excretion on the fifth day of each trial period. We analyzed the data with a mixed linear model that included the fixed effects of treatment (treated and control) and trial period, and the random effect of the cat. Compared with controls, cats treated with dapagliflozin had a significant increase in mean (±SE) glomerular filtration rate (3.1 ± 0.2 vs 2.5 ± 0.2 mL/kg/min; P = 0.01), whereas there were no significant differences in serum urea, creatinine and symmetric dimethylarginine, and 24-h urine sodium and chloride excretion. We propose that dapagliflozin-mediated delivery of sodium and glucose distal from the proximal convoluted tubule induced compensatory increased sodium absorption at the thick ascending loop of Henle that resulted in decreased sodium delivery to the distal tubule leading to tubuloglomerular feedback–mediated glomerular hyperfiltration. Future studies should determine if SGLT2is' renoprotective effect in people can be enhanced with the addition of a Na+-K+-Cl− diuretic and whether dapagliflozin will be useful in mitigating proteinuria and hypertension that follow glomerular hyperfiltration in diabetic companion animals in a similar mechanism as in people.

Objectives: To review the use of telehealth in subjects with diabetic foot ulcer; evaluating its clinical outcomes, diagnostic accuracy, cost-effectiveness and behavioural perceptions. Design: Systematic review. Setting: Selected studies were conducted in Australia, USA, the Netherlands, Denmark, Poland and UK. Participants: A total of 948 identified studies were evaluated against the inclusion criteria. Eleven eligible studies were included for review. Patients with diabetic foot ulcer had to have telehealth guided management. Main outcome measures: Telehealth systems were evaluated against at least one of the following: clinical implications on ulcer healing and disease prognosis; diagnostic accuracy; cost-effectiveness; behavioural perceptions among health professionals or patients. Result: Eleven eligible studies were included for review. Studies that evaluated telehealth against clinical outcomes were underpowered by study design, sample sizes and short duration follow-up. Telehealth systems demonstrated good intra- and inter-observer reproducibility, high diagnostic accuracy and agreement with live assessments. Authors rationalised the cost-effectiveness of their respective telehealth systems, but could not support this with long-term cost analysis. Both patient and health professionals responded positively towards telehealth in surveys and face-to-face interviews. Conclusion: Telehealth yields high diagnostic accuracy, reproducibility and positive behavioural perceptions. However, it is not clear if telehealth use in diabetic foot management has favourable clinical and economic outcomes. More long-term prospective controlled trials on larger populations are needed to further characterise our findings.

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.

Background: The outcomes of telehealth in the management of type 2 diabetes (T2DM) have not been evaluated since the publication of recent clinical trials. Objective: To conduct a systematic review and meta-analysis of recently published randomized controlled trials (RCTs) to assess the biochemical, clinical and psychosocial outcomes of telehealth in subjects with T2DM. Methods: Electronic databases, MEDLINE, CINAHL, INFORMIT, SCOPUS and the Cochrane Central Register of Controlled Trials and reference lists of existing systematic reviews were searched until August 2017 to identify relevant studies. Study search and selection were performed by two independent reviewers. 4791 articles were retrieved of which 11 RCTs (n=3772) were included. A meta-analysis with random effects model was applied to estimate the pooled results. Results: Telehealth was associated with a statistically significant and clinically relevant absolute decline in glycosylated haemoglobin (HbA1c) compared to usual care (mean difference -0.17%; 95% CI -0.25 to -0.09%; p Conclusion: Telehealth interventions were associated with improved glycaemic control (HbA1c) in T2DM diabetic patients. However, no clinically relevant impact was observed on lipid profile, blood pressure, body mass index and psychosocial well-being. Future studies should seek to evaluate the effect of intervention duration on HbA1c, psychosocial outcomes and the effectiveness of telehealth in rural and underserved populations. Disclosure N. Nangrani: None. U. Malabu: None. V. Vangaveti: None.

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.

Background: Hyponatremia is known to be common electrolyte disturbance in the hospitalized patients. Yet there is no record on its magnitude in tropical Asia Pacific Australia in spite of higher risk due to associated endemic tropical infectious diseases. Objective: The aim of the study was to determine prevalence of hyponatremia in acute medical admissions in Northern Australasia. Design, setting and participants: We studied 469 consecutive acute medical admissions to a hospital in Australia's Far North Queensland during the colder months of June and July 2012. Main outcome measures: Prevalence of hyponatremia and its relationship with gender, age, diagnosis and prognosis in acute medical admissions. Results: On admission, hyponatremia (plasma sodium < 136 mmol/l) was present in 39.4% of patients, with mild (130 - 135), moderate (126 - 129 mmol/l) and severe (< 126 mmol/l) hyponatremia being present in 25.2 %, 10.7% and 3.6% respectively. Overall, adding together admission hyponatremia with that developing during admission, 45.2% of patients were affected with 11.5% and 4.1% having moderate or severe hyponatremia. Hypokalemia and hyperkalemia were present in 17% and 18.1% respectively. Overall, 275/469 patients (58.6%) presented with an electrolyte abnormality. There were significant correlations of hyponatremia with age but with gender and in-hospital mortality. Prevalence of hyponatremia was high across all diagnostic categories. Conclusions: The prevalence of hyponatremia appears to be high in the tropical North Australian population, this being the highest prevalence reported amongst acute hospital admissions. The previously reported correlations with age and mortality do appear to hold good for this population with a high prevalence of electrolyte disorders. Our data being a pilot study further prospective analysis on a larger population in the area is needed to confirm 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.

Thyroid disturbances are common in women during the reproductive years of their lives. Autoimmunity and altered iodine status together account for a high proportion of the abnormalities. Autoimmune thyroid disease is present in around 4% of young females, and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on the one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum on the other hand. Suboptimal iodine status affects a large proportion of the world's population, and pregnancy further depletes iodine stores. There is controversy surrounding the degree to which iodine should be supplemented and the duration of supplementation. Recent studies have helped to clarify the relationship between maternal thyroid status and neuropsychological development of the child. The role of other environmental factors including smoking and selenium status is also now recognised. Universal screening for thyroid hormone abnormalities is not routinely recommended at present. However, measurement of thyroid function and autoantibodies should certainly be considered in those who are at high risk of thyroid disease and in those whose pregnancy is otherwise high risk. The practicing clinician needs to be aware of the thyroid changes which accompany pregnancy.

Severe illness can lead to multiple transient endocrinopathies. In adult patients, neuroendocrine alterations include sick euthyroid syndrome, an increase in corticosteroid levels, increase in prolactin levels, decreased insulin growth factor 1 levels and hypogonadism. We report the case of a 24-year-old man with meningococcal sepsis with multiple end-organ complications who developed persistent non-autoimmune hypothyroidism, adrenal insufficiency and primary hypogonadism all requiring hormone replacement. While adrenal insufficiency as part of the Waterhouse-Friderichsen syndrome is well described, reports of primary hypothyroidism and persistent primary hypogonadism in severe illness are exceedingly rare. Multiple combined endocrinopathies as in this case have not been reported previously. This case highlights the necessity of screening for endocrine abnormalities in severe illness and the need for treatment if persistent. It also raises a novel concept of meningococcal sepsis causing multiple endocrinopathies possibly via disseminated intravascular coagulopathy-related ischaemic damage.

[Extract] The prevalence of obesity is increasing globally. This with the aging population structure accounts for the increased prevalence of chronic diseases associated with obesity. For example, the number of people with diabetes in the world is projected to reach 300 million before 2025. Through childhood, adolescence, and adult life, obesity prevalence increases with age. However, the elderly (aged 60 plus), have a lower prevalence and in the extreme elderly (aged 80 plus), it is only a third of that in middle life. Obesity in the elderly presents a distinct problem. As at younger ages, it is associated with chronic diseases, and with functional and cognitive decline. However, the prevalence of being underweight is also a high and is itself a marker for poor health and functional decline. The ideal body weight and composition for elderly populations has yet to be defined. Weight management should be a target for certain elderly individuals whose health is at risk. However, in the elderly is important to maintain an optimal body composition as well as weight. Elderly individuals with weight-related diseases such as type 2 diabetes represent an obvious target for weight management. It is, in practice, difficult to identify elderly patients who would benefit from weight management programmes. The various components of the metabolic syndrome (MS) become more common with aging. Drugs to decrease cardiovascular risk and to treat diabetes and the other chronic diseases of aging have improved in recent years. The elderly are frequently prescribed complex drug regimens with which they often comply poorly, derive little benefit, and experience a high risk of adverse reactions and drug interactions. Although it is clear that obesity should be treated in high-risk elderly patients, pharmacotherapy and surgery do not have an evidence base specific to the elderly. There is emerging evidence to guide us with dietary and exercise therapy (1, 2). This review attempts to define the situations in which management of obesity is indicated, and to summarise what is known, and what is emerging, about the various treatment options.

The aim of the study was to determine surgical indication and complication of subtotal thyroidectomy in patients being treated for Graves' disease at King Khalid University Hospital Riyadh Saudi Arabia in the period between January 1996 and December 2005. Twenty-five out of 194 adult patients with Graves' disease had thyroidectomy for hyperthyroidism during the 10-year period representing 13% comprising 11 males and 14 females. Mean age at presentation for all the patients was 28±12 years. Males had higher serum T4 77.7±20.7 than females 49.8±21.9 pmol L-1; p

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.

Background: Te objective of the study was to determine whether serum levels of procollagen type 1 N propeptide (P1NP), a bone formation turnover marker, di?ers between diabetic foot ulcer with osteomyelitis (DFO) and diabetic foot ulcers without osteomyelitis serving as controls. It was also aimed to assess the usefulness of P1NP in diagnosing DFO compared to other common in?ammatory markers. Materials and Methods: A case–control study was designed comparing the aforementioned groups. Patients were classifed as osteomyelitis and controls based on the International Working Group diagnostic criteria. Serum P1NP and three other in?ammatory markers, namely, C?reactive protein (CRP), white blood cells (WBC), and platelets were analyzed on patients with DFO and ontrols. Results: Te mean serum P1NP levels were signifcantly higher in the DFO group ( n : 16), 10.5 ± 5.2 (ng/ml), than the control group ( n : 11) 3.1 ± 2.8 (ng/ml), P = 0.001. P1NP showed the highest sensitivity/specifcity 86.7%/80% compared to 70.6%/80%, 56.2%/45.4%, and 50%/37% for CRP, WBC and platelets, respectively. Receiver operator characteristic curves showed the best value of area under the curve of 0.9 for P1NP compared to 0.85, 0.54, and 0.46 for CRP, WBC, and platelets. Conclusion: We found marked elevation of serum P1NP in diabetic foot ulcer with bone infection with potential value in using it to diagnose DFO.

Linoleic acid (LA) is a major constituent of low-density lipoproteins. An essential fatty acid, LA is a polyunsaturated fatty acid, which is oxidised by endogenous enzymes and reactive oxygen species in the circulation. Increased levels of low-density lipoproteins coupled with oxidative stress and lack of antioxidants drive the oxidative processes. This results in synthesis of a range of oxidised derivatives, which play a vital role in regulation of inflammatory processes. The derivatives of LA include, hydroxyoctadecadienoic acids, oxo-​octadecadienoic acids, epoxy octadecadecenoic acid and epoxy-keto-octadecenoic acids. In this review, we examine the role of LA derivatives and their actions on regulation of inflammation relevant to metabolic processes associated with atherogenesis and cancer. The processes affected by LA derivatives include, alteration of airway smooth muscles and vascular wall, affecting sensitivity to pain, and regulating endogenous steroid hormones associated with metabolic syndrome. LA derivatives alter cell adhesion molecules, this initial step, is pivotal in regulating inflammatory processes involving transcription factor peroxisome proliferator-activated receptor pathways, thus, leading to alteration of metabolic processes. The derivatives are known to elicit pleiotropic effects that are either beneficial or detrimental in nature hence making it difficult to determine the exact role of these derivatives in the progress of an assumed target disorder. The key may lie in understanding the role of these derivatives at various stages of development of a disorder. Novel pharmacological approaches in altering the synthesis or introduction of synthesised LA derivatives could possibly help drive processes that could regulate inflammation in a beneficial manner. Chemical Compounds: Linoleic acid (PubChem CID: 5280450), 9- hydroxyoctadecadienoic acid (PubChem CID: 5312830), 13- hydroxyoctadecadienoic acid (PubChem CID: 6443013), 9-oxo-​octadecadienoic acid (PubChem CID: 3083831), 13-oxo-​octadecadienoic acid (PubChem CID: 4163990), 9,10-epoxy-12-octadecenoate (PubChem CID: 5283018), 12,13-epoxy-9-keto-10- trans -octadecenoic acid (PubChem CID: 53394018), Pioglitazone (PubChem CID: 4829).

We present a case of highly elevated tenfold rise of serum chromogranin A in a young, morbidly obese, hypertensive female being investigated for pancreatic mass, weight loss, and elevated ESR. Following extensive noninvasive investigations, an ultrasound-guided pancreatic biopsy confirmed benign haemorrhagic cyst. A clue to the etiology of the hyperchromogranin A was the elevated serum gastrin level leading to suspicion of proton pump inhibitor administration confirmed by admittance to its use. Withdrawal of the medication led to dramatic resolution of the neuroendocrine tumor marker.

Summary Our patient had drainage of a large amoebic liver abscess. This got complicated by a severe degree of hypotension, which required aggressive fluid resuscitation and hydrocortisone support. Computerised tomography (CT) of the abdomen revealed bilateral adrenal gland haemorrhage (BAH) resulting in primary adrenal gland failure, which was the cause for hypotension. Patient was on long-term warfarin for provoked deep vein thrombosis of lower limb, which was discontinued before the procedure. Thrombophilia profile indicated the presence of lupus anticoagulant factor with prolonged activated partial thromboplastin time (aPTT). Patient was discharged on lifelong warfarin. This case emphasises the need for strong clinical suspicion for diagnosing BAH, rare but life-threatening condition, and its association with amoebic liver abscess and anti-phospholipid antibody syndrome (APLS). Learning points Recognition of BAH as a rare complication of sepsis. APLS can rarely cause BAH.

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.

Macrophage apoptosis, a key process in atherogenesis, is regulated by oxidation products, including hydroxyoctadecadienoic acids (HODEs). These stable oxidation products of linoleic acid (LA) are abundant in atherosclerotic plaque and activate PPARγ and GPR132. We investigated the mechanisms through which HODEs regulate apoptosis. The effect of HODEs on THP-1 monocytes and adherent THP-1 cells were compared with other C18 fatty acids, LA and α-linolenic acid (ALA). The number of cells was reduced within 24 hours following treatment with 9-HODE (p < 0.01, 30 μM) and 13 HODE (p < 0.01, 30 μM), and the equivalent cell viability was also decreased (p < 0.001). Both 9-HODE and 13-HODE (but not LA or ALA) markedly increased caspase-3/7 activity (p < 0.001) in both monocytes and adherent THP-1 cells, with 9-HODE the more potent. In addition, 9-HODE and 13-HODE both increased Annexin-V labelling of cells (p < 0.001). There was no effect of LA, ALA, or the PPARγ agonist rosiglitazone (1μM), but the effect of HODEs was replicated with apoptosis-inducer camptothecin (10μM). Only 9-HODE increased DNA fragmentation. The pro-apoptotic effect of HODEs was blocked by the caspase inhibitor DEVD-CHO. The PPARγ antagonist T0070907 further increased apoptosis, suggestive of the PPARγ-regulated apoptotic effects induced by 9-HODE. The use of siRNA for GPR132 showed no evidence that the effect of HODEs was mediated through this receptor. 9-HODE and 13-HODE are potent—and specific—regulators of apoptosis in THP-1 cells. Their action is PPARγ-dependent and independent of GPR132. Further studies to identify the signalling pathways through which HODEs increase apoptosis in macrophages may reveal novel therapeutic targets for atherosclerosis.

Antibody to hepatitis C virus (anti-HCV) was detected in 18.7% of patients with hepatocellular carcinoma (HCC) and in 10.9% of controls (P < 0.001). The corresponding prevalences of hepatitis B surface antigen (HBsAg) were 59.3% and 50.0% (P < 0.001). Using patients with non-hepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio 6.88%; 95% confidence interval [CI] 1.63-9.77) and HBsAg (odds ratio 6.46; 95% CI 1.68-18.13) were independent risk factors for HCC. Calculation of the incremental odds ratio indicated no interaction between hepatitis B virus (HBV) and HCV. Blood transfusion was a significant risk factor for acquiring HCV infection with odds ratios of 5.48 (95% CI 1.07-29.0) and 2.86 (95% CI 1.31-22.72) for HCC cases and controls, respectively. The mean age of HCC cases with HBsAg and anti-HCV was lower than that of HCC patients with anti-HCV alone (P < 0.01). It is concluded that there is a high rate of HBV infection, and a low rate of HCV infection, among Nigerian patients with HCC. However, HBV and HCV are independent risk factors for the development of HCC, with HBV having an effect more rapidly. Screening of blood products for transfusion might minimize the risk of HCV transmission.

Objective: Stromal cell-derived factor-1 (SDF-1) is expressed in pre-adipocytes but its role is unknown. We investigated butyrate (a histone deacetylase inhibitor - HDACi) and other short-chain fatty acids (SCFA) in the regulation of SDF-1. We further investigated whether effects of SCFA were signalled through G protein-coupled receptors FFA2 and FFA3. Design and Results: SDF-1 mRNA expression and protein secretion were studied in 3T3-L1 cells and human pre-adipocytes. SDF-1 was abundant, with mRNA and protein levels increased by butyrate. This was replicated with acetate and propionate, but not by trichostatin or valproate. Trichostatin inhibited SDF-1 secretion. Pertussis toxin blocked stimulation by butyrate. The order of potency of SCFA in stimulating SDF-1 (C3 > C4 > C2) is consistent with action through FFA3. Silencing the FFA3 gene abolished butyrate-stimulated SDF-1 expression and secretion. FFA3 was expressed in both pre-adipocytes and adipocytes, while FFA2 was expressed in adipocytes only. SDF-1 expression was low in murine macrophage J774.2 cells, while the SDF-1 receptor CXCR4 was absent from 3T3-L1 cells but abundant in J774.2 macrophages. In human pre-adipocytes, FFA3 was also expressed and SCFA increased SDF-1 secretion. Conclusions: SDF-1 and CXCR4 may mediate the interaction between adipose stromal cells and macrophages. Effects of SCFA are mediated through FFA3, but not histone deacetylase inhibition.

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).

The aim was to report an unusual case of insulinoma presenting with long-standing depression and primary testicular failure. We describe a 34-year-old male with clinical, laboratory, and radiologic data consistent with islet cell tumor and seminiferous tubule failure primary hypogonadism. The literature is reviewed relative to the component of this syndrome, and a possible association is discussed. The subject was investigated for a long-standing history of depression requiring medical attention because of mental confusion and slurred speech and was found to have an insulinoma. He was diagnosed with primary gonadal failure and physical examination showed no evidence of dysmorphic features. Chromosomal analysis revealed normal 46 XY and testicular biopsy showed Sertoli cell only syndrome (SCOS). Biochemistry revealed endogenous hyperinsulinism and histology confirmed an islet cell tumor. He remained euglycemic postoperatively and on followup. From this report, we emphasize drawing clinicians' attention to the possibility of an association between insulinoma and primary testicular failure and suggest consideration of this diagnosis in patients with hypergonadotropic hypogonadism who may present with infertility.

Background. Calcific uremic arteriolopathy (CUA) or calciphylaxis though generally noted for its high mortality, recent case reports have shown promising results using single agent therapies. However, it is not clear whether combination therapeutic agents will improve course of the disease.Objective. To determine clinical outcome in subjects with CUA on multimodal treatment.Methods. All patients with end-stage renal failure (ESRF) at The Townsville Hospital, Australia, from April 1, 2006, to March 31, 2011, with diagnosis of CUA were retrospectively studied.Results. Six subjects with CUA (4 females and 2 males) were on various combination therapeutic agents comprising sodium thiosulphate, hyperbaric oxygen, prednisolone, cinacalcet, and parathyroidectomy in addition to intensified haemodialysis, specialist local wound care, and antibiotics. The wounds failed to heal in 3 patients while 5 of the 6 subjects died; cause of death being sepsis in 3 and myocardial infarction in 2.Conclusion. Prognosis of CUA remains poor in spite of multimodal combination therapy. Further prospective studies on a larger population are needed to verify our findings.

Objective: o present an unusual case of calciphylaxis in an obese patient with inactive rheumatoid arthritis and normal renal function. Methods: We describe a 46-year-old morbidly obese Caucasian woman who had previously weighed 200 kg and presented with painful leg ulcers following a rapid weight loss of 102 kg in 1 year. Results: The subject was admitted with a 6-week history of painful leg ulcers that progressed to her thighs. Vasculitis and active rheumatoid arthritis were excluded clinically and biochemically. A skin biopsy confirmed calciphylaxis in the context of normal renal function. Serum 25-hydroxyvitamin D was low at 14 ng/mL (reference range, 20 to 200 ng/mL), with an elevated serum parathyroid hormone level of 241 pg/mL (reference range, 10 to 65 pg/mL), but normal serum calcium and phosphorus levels. The skin lesions persisted despite local wound care, daily hyperbaric oxygen, and parenteral sodium thiosulfate therapies. After normalizing the serum vitamin D level through oral supplementation, she responded well to pamidronate infusion with complete healing of the ulcers and regained 13% of her premorbid weight. Conclusion: This is the first case of calciphylaxis preceded by weight loss of greater than 100 kg in a patient with hypovitaminosis D who responded to pamidronate therapy.

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.

Background: To determine causes of short stature (SS) in adult endocrine service at a Saudi Arabian tertiary center. Methods: A retrospective analysis was made of data from 104 subjects who were primarily evaluated for causes of SS in the endocrinology unit of King Khalid University Hospital Riyadh from January 1997 to December 2006. Results: Growth hormone deficiency (GHD) and normal variant short stature (NVSS) were the leading causes of SS contributing 90 subjects (86%; 43% for each), followed by celiac disease in 4 subjects (4%). Other etiologies of short stature included primary hypothyroidism, diabetes mellitus, and Turner's syndrome (2% each). Conclusion: We conclude that GHD and NVSS are the commonest causes of SS in Saudi Arabia. In view of the need to differentiate the two major etiologies, it is suggested that growth hormone stimulatory tests be conducted on all patients with SS associated with delayed bone age. Further prospective study in a larger population is needed to characterize this finding.

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

Hirsutism among women of fertile age is commonly seen in clinical practice, but the pattern of the disease in Saudi Arabs has not been studied. The aim of the study was to determine the clinical, biochemical and etiologic features of hirsutism in Saudi females.101 Saudi Arab women presenting with hirsutism at King Khalid University Hospital, Riyadh, Saudi Arabia, from 1 January 2000 to 31 December 2005 were prospectively assessed using the recently approved diagnostic guidelines for hyperandrogenic women with hirsutism.Polycystic ovary syndrome (PCOS) was the cause of hirsutism in 83 patients (82%) followed by idiopathic hirsutism (IH) in 11 patients (11%). Others causes of hirsutism included late onset congenital adrenal hyperplasia in 4 patients (4%), microprolactinoma in 2 (2%) and Cushingâs syndrome in 1 (1%) patient. Age at presentation of PCOS was 24.5+/-6.6 years (mean+/-SD) and 51% of the subjects were obese. Furthermore, 74 (89%) of patients with PCOS had an oligo/anovulatory cycle while the remaining 9 patients (11%) maintained normal regular menstrual cycle. Luteinizing hormone and total testosterone were significantly higher in patients with PCOS than in those with IH (P.05).The present data show PCOS to be the commonest cause of hirsutism in our clinical practice and PCOS is prominent amongst young obese females. However, further studies on a larger scale are needed to verify our findings.

[Extract] Recently Haase et al [1] reported that maternal low-protein diet in rats was associated with decreased beta cell mass and decreased expression of growth arrest specific protein 6 (GAS6) in islets of Langerhans, and that incubation of neonatal islets with GAS6 enhanced beta cell proliferation. Low beta cell mass early in life is associated with increased future risk of type 2 diabetes. Consistent with a protective effect of GAS6, the c.834+7G>A polymorphism is associated with type 2 diabetes risk in humans [2]. The AA phenotype is associated with higher levels of GAS6, lower glucose levels, and decreased diabetes risk. Currently used drugs affecting the incretin axis have stimulated interest in therapeutic approaches that either preserve or enhance beta cell mass or function, and GAS6 (secreted by alpha cells) is, therefore, an attractive therapeutic target.

[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.