Cushing’s disease: does low-dose pasireotide offer a comparable efficacy and safety to high-dose?

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

High rate of diabetes in the Asia-Pacific Island: possible role of rapid urbanization: a hospital based study

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 <0.05. Majority of the patients were of young population aged <50 years representing 72 % of the cohort and predominantly of coastal province of origin. Almost 3/4th of the study population was based in Kimbe town and its suburb with only 32 subjects (25.6%) identified as rural residents; p<0.05. This study suggests that subjects living in Asia-Pacific area of rapid urbanization are at higher risk of diabetes compared to residents of rural areas. It highlights the need for adequate health planning and education as part of urbanization program in the DM-prone Asia-Pacific population. Further prospective studies are needed to verify our findings

Lower extremity amputations and long-term outcomes in diabetic foot ulcers: a systematic review

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

Response to: comment on “prevalence and risk factors for siabetic lower limb amputation: a clinic-based case control study”

[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]

Prevalence and risk factors for diabetic lower limb amputation: a clinic-based case control study

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

Blockade of mini-TrpRS for treatment of diabetic foot syndrome

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

Obesity in the elderly diabetic patients: Townsville Hospital experience

Background / Aims: Although the increase in the prevalence of obesity among Australian diabetics (DM) generally is well documented, little information has been published specifically about the situation among older Australians living in North Queensland. This is despite the reportedly growing geriatric population in the region. The main aim of the study is to determine prevalence of obesity in the elderly subjects with DM. Methods: Hospital-based cross sectional study was prospectively conducted on patients admitted at the Townsville Hospital aged >70 years. Questionnaire was administered and anthropometric measurements were recorded in subjects with DM (study group) and non-DM (control group). Results: Data of 68 subjects were analysed comprising of 31 DM and 37 non-DM. Prevalence of obesity (BMI>25 kg/m2) was 74.7% compared with 45.9% in non-DM X2 = 5.6, P = 0.018. The mean BMI and body weight were higher in DM than in non-DM, 28.2 + 6.7 vs 25 .2 + 5.3 kg/m2 and 78.5 + 18 vs 68.6 + 17 kg, both P < 0.05. Gender, mean age, and prevalence of other co -morbidities were similar in both groups. Conclusion: We report high prevalence of obesity in diabetes elderly population. Prevention of DM may likely reduce rate of over weight in our geriatric subjects. This being pilot project further prospective studies on a larger population are needed to confirm our findings

Atypical tibial fracture in a 63-Year-old woman with intermittent use of bisphosphonate unmasking hypophosphatasia

We report an unusual case of atypical proximal tibial stress fracture (APTF) associated with intermittent use of bisphosphonates (BPs) and persistently low serum alkaline phosphatase (ALP) levels. We describe the case of a 63-year-old white woman who had experienced an APTF after 4 years of intermittent exposure to alendronate given for recurrent metatarsal stress fractures. BP administration was stopped after the diagnosis of the APTF. A review of her previous serum ALP levels revealed they had been consistently low. Adult hypophosphatasia (HPP) was diagnosed by the low serum ALP activity and elevated urine phosphoethanolamine levels. She was treated conservatively with analgesics. Adult HPP is an underrecognized condition associated with atypical insufficiency fractures, and BP use compounds this risk. To the best of our knowledge, we report the first case of intermittent BP exposure preceding an APTF in an adult patient with HPP, highlighting the uncommon site of the proximal tibia for BP-associated atypical insufficiency fractures, the need to screen for HPP in those with persistently low ALP levels before they begin BP therapy, and the importance of avoiding BP use in those with HPP

Prevalence and risk factors of lower limb amputation in patients with end-stage renal failure on dialysis: a systematic review

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

Effect of glucagon-like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Aims: To determine the effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on albuminuria in adult patients with type 2 diabetes mellitus (T2DM). Methods: Medline Ovid, Scopus, Web of Science, EMCARE and CINAHL databases from database inception until 27 January 2022. Studies were eligible for inclusion if they were randomized controlled trials that involved treatment with a GLP-1RA in adult patients with T2DM and assessed the effect on albuminuria in each treatment arm. Data extraction was conducted independently by three individual reviewers. The PRISMA guidelines were followed regarding data extraction and quality assessment. Data were pooled using a random effects inverse variance model and all analysis was carried out with RevMan 5.4 software. The Jadad scoring tool was employed to assess the quality of evidence and risk of bias in the randomized controlled trials. Results: The initial search revealed 2419 articles, of which 19 were included in this study. An additional three articles were identified from hand-searching references of included reviews. Therefore, in total, 22 articles comprising 39 714 patients were included. Meta-analysis suggested that use of GLP1-RAs was associated with a reduction in albuminuria in patients with T2DM (weighted mean difference −16.14%, 95% CI −18.42 to −13.86%; p < .0001) compared with controls. Conclusions: This meta-analysis indicates that GLP-1RAs are associated with a significant reduction in albuminuria in adult patients with T2DM when compared with placebo