10 research outputs found
The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality
No full textSince the introduction of combined antiretroviral therapy (cART) and more effective treatments for AIDS, there has been a dramatic shift from the weight loss and wasting that characterised HIV/AIDS (and still does in countries where cART is not readily available or is initiated late) to healthy weight, or even overweight and obesity at rates mirroring those seen in the general population. These trends are attributable to several factors, including the “return to health” weight gain with reversal of the catabolic effects of HIV-infection following cART-initiation, strategies for earlier cART-initiation in the course of HIV-infection which have prevented many people living with HIV-infection from developing wasting, in addition to exposure to the modern obesogenic environment. Older cART regimens were associated with increased risk of body fat partitioning disorders (lipodystrophy) and cardiometabolic complications including atherothrombotic cardiovascular disease (CVD) and diabetes mellitus. Whilst cART now avoids those medications implicated in causing lipodystrophy, long-term cardiometabolic data on more modern cART regimens are lacking. Longitudinal studies show increased rates of incident CVD and diabetes mellitus with weight gain in treated HIV-infection. Abdominal fat gain, weight gain, and rising body mass index (BMI) in the short-term during HIV treatment was found to increase incident diabetes risk. Rising BMI was associated with increased risk of incident CVD, however the relationship varied depending on pre-cART BMI category. In contrast, a protective association with mortality is evident, predominantly in the underweight and in resource-poor settings, where weight gain reflects access to cART and virological suppression. The question of how to best evaluate, manage (and perhaps constrain) weight gain during HIV treatment is of clinical relevance, especially in the current climate of increasingly widespread cART use, rising overweight, and obesity prevalence and growing metabolic and cardiovascular disease burden in people living with HIV-infection. Large prospective studies to further characterise the relationship between weight gain during HIV treatment and risk of diabetes, CVD and mortality are required
The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality
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Table_1_Ramadan Fasting and Maternal and Fetal Outcomes in Pregnant Women with Diabetes Mellitus: Literature Review.docx
No full textThere is an emerging Muslim and diabetic population in the United States and other Western countries and majority of pregnant women and patients with diabetes mellitus choose to fast during Ramadan. Fasting during Ramadan in pregnant women with diabetes may represent a ‘perfect storm’ of metabolic disturbances including hyperglycemia, hypoglycemia and ketosis. Recent continuous and flash glucose monitoring data suggests increased glycemic variability (fasting hypo- and post-Iftar hyperglycemia) in non-pregnant patients with diabetes during Ramadan. Only five small-scale studies, predominantly focused on women with gestational diabetes mellitus in Muslim-majority nations have explored maternal glycemic outcomes during Ramadan which is associated with lower mean blood glucose levels and higher frequency of fasting hypoglycemia. Data is limited however on important clinical outcomes such as symptomatic and serious hypoglycemia requiring hospitalization. Results have been conflicting regarding maternal Ramadan fasting and association with fetal outcomes in women without diabetes. Only one recently published study reported on perinatal outcomes in pregnant women with gestational diabetes which found no effect of Ramadan exposure on mean birthweight or macrosomia frequency but lower neonatal hypoglycemia prevalence, however a significant limitation was lack of documentation of maternal fasting status. At this stage, due to paucity of data, the current medical recommendation is against Ramadan fasting for pregnant Muslim women with diabetes. Large-scale population-based studies are warranted regarding maternal and fetal outcomes in pregnant fasting women with diabetes and such studies should characterize maternal fasting status and have meaningful and consistent clinical outcomes. High-quality data derived from these studies can assist clinicians in providing more evidence-based advice to safely navigate both mother and fetus through a potentially challenging pregnancy.</p
Diabetes among Māori women with self-reported past gestational diabetes mellitus in a New Zealand Māori community
No full textBackground: Gestational diabetes mellitus (GDM) is a risk factor for subsequent development of type 2 diabetes mellitus (T2DM). We have investigated the extent of this risk among Māori women without known diabetes. Materials and methods: We recruited 2786 Māori women aged 28–86 years between 2004 and 2006, without diagnosed diabetes from the Waikato and Southern Lakes regions, via media, community and general practitioner channels, and invited them for an oral glucose tolerance test (OGTT). Results: Fifty (1.8%) women reported previous GDM (pGDM). The prevalence decreased significantly with age (P = 0.009). Women aged <50 years with pGDM had higher body mass index (35.6 ± 6.7 vs 32.4 ± 7.7 kg/m2, P < 0.01), waist circumference (105.3 ± 18.8 vs 96.9 ± 16.6 cm, P < 0.01), fasting blood glucose (5.5 ± 1.0 vs 5.1 ± 0.8 mmol/L, P ≤ 0.01), two-hour post-prandial blood glucose (6.6 ± 3.0 vs 5.6 ± 2.1 mmol/L, P < 0.01) and HbA1c (6.0 ± 0.8 vs 5.8 ± 0.6%, P < 0.05) than women without pGDM. PGDM was a significant risk factor for undiagnosed diabetes (odds ratio 4.0; (5% confidence interval 1.67–9.71). Undiagnosed diabetes was significantly more prevalent among women with than without pGDM aged <40 years (20.0% vs 1.5%). Conclusion: Self-reported past GDM was a significant risk factor for undiagnosed diabetes in this Māori population, particularly among women aged <40 years, highlighting the importance of targeting this group for more intensive screening
Hypercalcaemia secondary to hypophysitis and cortisol deficiency: another immunotherapy-related adverse event
No full textHypercalcaemia is a common complication seen in malignancy, frequently due to paraneoplastic parathyroid hormone-related peptide production or osteolytic bony metastases. We present a 58-year-old female with immunotherapy-mediated hypophysitis causing secondary cortisol deficiency resulting in severe glucocorticoid-responsive hypercalcaemia. Whilst hypophysitis is a well recognised adverse event in those receiving immunotherapy for advanced malignancy, it does not typically present with hypercalcaemia. The mechanism responsible for hypercalcaemia due to hypocortisolaemia has not been fully elucidated although hypotheses include the effects of volume depletion and thyroxine’s action on bone. Prompt treatment with glucocorticoids caused an improvement in the patient’s symptoms and corrected her hypercalcaemia which later returned after an attempted glucocorticoid wean. With the increasing uptake of immunotherapy, clinicians should be aware of this unusual presentation of immunotherapy-related hypophysitis and secondary hypocortisolaemia which can be life-threatening if the diagnosis is delayed
Table_1_Case Report: Hypoglycemia Due to Metastatic Insulinoma in Insulin-Dependent Type 2 Diabetes Successfully Treated With 177 Lu-DOTATATE.docx
No full textWe describe a 96-year-old man with insulin-dependent type 2 diabetes mellitus who, despite insulin cessation, presented with recurrent hypoglycemia associated with confirmed inappropriate endogenous hyperinsulinemia. 68Ga-DOTATATE-PET/CT scans demonstrated increased uptake in the pancreatic tail with multiple large intensely active liver metastases. Liver biopsy confirmed the diagnosis of well-differentiated metastatic neuroendocrine tumor. He was unsuitable for surgical resection and long-acting somatostatin analog therapy was ineffective. Subsequent management with four cycles of Lutate [177-Lutetium-DOTA0-Tyr3-octreotate (177Lu-DOTATATE)] resulted in resolution of hypoglycemia and ongoing clinical, biochemical, and radiological response 6 years after. This case is unique due to not only the paradoxical entity of insulinoma in insulin-dependent diabetes but also the positive sustained outcome after 177Lu-DOTATATE, given that unresectable metastatic insulinoma carries a poor prognosis. We review published cases of metastatic insulinoma in patients with diabetes mellitus as well as the literature to-date investigating efficacy and safety of Lutate therapy in metastatic insulinoma.</p
Exercise for postmenopausal bone health – Can we raise the bar?
No full textPurpose of Review: This review summarises the latest evidence on effects of exercise on falls prevention, bone mineral density (BMD) and fragility fracture risk in postmenopausal women, explores hypotheses underpinning exercise-mediated effects on BMD and sheds light on innovative concepts to better understand and harness the skeletal benefits of exercise. Recent Findings: Multimodal exercise programs incorporating challenging balance exercises can prevent falls. Emerging clinical trial evidence indicates supervised progressive high-intensity resistance and impact training (HiRIT) is efficacious in increasing lumbar spine BMD and is safe and well-tolerated in postmenopausal women with osteoporosis/osteopenia. There remains uncertainty regarding durability of this load-induced osteogenic response and safety in patients with recent fractures. Muscle-derived myokines and small circulating extracellular vesicles have emerged as potential sources of exercise-induced muscle-bone crosstalk but require validation in postmenopausal women. Summary: Exercise has the potential for multi-modal skeletal benefits with i) HiRIT to build bone, and ii) challenging balance exercises to prevent falls, and ultimately fractures. The therapeutic effect of such exercise in combination with osteoporosis pharmacotherapy should be considered in future trials
Periprocedural effects of statins on the incidence of contrast-induced acute kidney injury : a systematic review and trial sequential analysis
No full textBackground: Contrast-induced acute kidney injury (CI-AKI) is a potential complication in coronary angiography (CAG) and percutaneous coronary interventions (PCI). Prior randomized controlled trials (RCTs) have suggested that statins may play a role in reducing rates of CI-AKI, however it is not clear how firm the current evidence is. Objectives: The aim of this study was to conduct a meta-analysis and trial sequential analysis to determine the effects of statins in lowering CI-AKI rates in CAG and PCI. Methods: A systematic literature search was performed to include all RCTs comparing statins (treatment arm) versus low-dose statins or placebo (control arm) as pretreatment for CAG and/or PCI. A traditional meta-analysis and several subgroup analyses were conducted using traditional meta-analysis with relative risk (RR), trial sequential analysis, and meta-regression analysis. Results: 14 RCTs met our inclusion criteria giving a total of 2992 statin treated (49.6%) and 3041 control patients (50.4%). There was a significant reduction in CI-AKI in the statin group compared to controls (3.7% vs 8.3%, RR, 0.46; p = < 0.00001). Trial sequential analysis using a relative risk reduction threshold of 20%, power 80% and type 1 error of 5%, indicated that the evidence is firm. A greater risk reduction in CI-AKI in the statin group significantly correlated with higher estimated glomerular filtration rate (eGFR; p = 0.003) Conclusions: The present trial sequential analysis provides support for statins in reducing the incidence of CI-AKI in patients undergoing CAG/PCI. This effect appeared to be greater in patients with higher eGFR.10 page(s
Study protocol for the ROLEX-DUO randomised placebo-controlled trial: ROmosozumab Loaded with EXercise – DUal effects on bone and muscle in postmenopausal Osteoporosis and Osteopenia
No full textIntroduction Novel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance the therapeutic effects of osteoporosis pharmacotherapy has not been established. ROLEX-DUO is a randomised controlled trial designed to assess the efficacy of romosozumab on various bone and muscle outcomes in combination with different exercise interventions in women with postmenopausal osteoporosis/osteopenia.
Methods and analysis ROLEX-DUO is an 8-month randomised placebo-controlled trial conducted at two tertiary referral centres for patients with osteoporosis/osteopenia in Sydney, New South Wales, Australia. The study is implementing the combination of romosozumab or placebo with different forms of exercise in postmenopausal women with osteoporosis/osteopenia without recent fragility fracture (n=102). Eligible women will be randomised 1:1:1 into one of three groups: (1) romosozumab with supervised HiRIT, (2) romosozumab with unsupervised low-intensity exercise or (3) placebo with unsupervised low-intensity exercise. Co-primary outcomes are the mean percentage change in lumbar spine bone mineral density (BMD), and mean change in five times sit-to-stand test performance (seconds) at 8 months. Secondary/exploratory outcomes include BMD changes at the femoral neck, total hip and distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) hip outcomes, DXA-derived lean and fat mass, serum markers of bone turnover (procollagen type 1 peptide, C-telopeptide of type 1 collagen) and bone biomarkers (dickkopf-1), serum extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom burden scores, number of falls and fractures. Mixed-effects models will be performed to compare longitudinal outcome results between groups using intention-to-treat analysis.
Ethics and dissemination The trial was approved by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants will provide written informed consent prior to inclusion. Findings will be disseminated via peer-reviewed journals, scientific conferences and summary reports to funding bodies.
Trial registration number ACTRN12623000867695.Full Tex
