Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) Trial: A Randomized Controlled Trial of Early Intervention With an Electronic Specialist-Led Model of Diabetes Care.

OBJECTIVE: To investigate the effect of early intervention with an electronic specialist-led "proactive" model of care on glycemic and clinical outcomes. RESEARCH DESIGN AND METHODS: The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) randomized controlled trial was performed at the Royal Melbourne Hospital. Eligible participants were adults admitted to a surgical ward during the study with either known diabetes or newly detected hyperglycemia (at least one random blood glucose result ≥11.1 mmol/L). Participants were randomized 1:1 to standard diabetes care or the intervention consisting of an early consult by a specialist inpatient diabetes team using electronic tools for patient identification, communication of recommendations, and therapy intensification. The primary outcome was median patient-day mean glucose (PDMG). The key secondary outcome was incidence of health care-associated infection (HAI). RESULTS: Between 12 February 2021 and 17 December 2021, 1,371 admissions met inclusion criteria, with 680 assigned to early intervention and 691 to standard diabetes care. Baseline characteristics were similar between groups. The early intervention group achieved a lower median PDMG of 8.2 mmol/L (interquartile range [IQR] 6.9-10.0 mmol/L) compared with 8.6 mmol/L (IQR 7.2-10.3 mmol/L) in the control group for an estimated difference of -0.3 mmol/L (95% CI -0.4 to -0.2 mmol/L, P < 0.0001). The incidence of HAI was lower in the intervention group (77 [11%] vs. 110 [16%]), for an absolute risk difference of -4.6% (95% CI -8.2 to -1.0, P = 0.016). CONCLUSIONS: In surgical inpatients, early diabetes management intervention with an electronic specialist-led diabetes model of care reduces glucose and HAI.

The Pro-Diab Melbourne Perioperative Study: A structured pre-admission perioperative diabetes management plan to improve medication usage in elective surgery.

BACKGROUND: Perioperative diabetes management has become increasingly complex; management is often inconsistent resulting in dysglycaemia and associated morbidity. AIM: To evaluate a structured pre-admission perioperative diabetes management plan (PDMP) for safe and appropriate recommendation, prescription and administration of diabetes medications in the perioperative period for people with diabetes undergoing elective, non-cardiac surgery. METHODS: A multidisciplinary team developed the intervention, a structured PDMP (including diabetes medication reconciliation, management guide, individualised plan) to standardise optimal perioperative diabetes management. A single centre prospective pre- and post-intervention pilot study was performed, including all individuals with diabetes medications attending the pre-admissions clinic during two 4-month periods (February to May) in 2016 (control period) and 2017 (intervention period). The primary outcome was appropriate recommendation, prescription and administration of diabetes medications (including insulin), according to the PDMP, in the perioperative period. Secondary outcomes measures were glycaemia. Analysis was by intention to treat. RESULTS: Control and intervention groups included 131 and 133 participants, respectively; they were well matched in clinical characteristics. The PDMP was completed correctly in 100 (75%) individuals in the intervention group. The appropriate use of diabetes medications increased from 30% in the control group to 71% in the intervention group (p < 0.001). Following the PDMP implementations, glycaemia improved in the overall perioperative period (8.7 ± 2.9 vs. 9.8 ± 3.3 mmol/L, p = 0.005) and at all time points (from admission and over entire hospital stay). CONCLUSION: A structured pre-admission perioperative diabetes management plan for elective surgery improved safe and appropriate diabetes medication use and glycaemia in the perioperative period.

End-of-Life Care Requires Caution with Use of Continuous Glucose Monitoring.

Use of medical device technologies for diabetes mellitus, including continuous glucose monitoring devices, is becoming more frequently encountered in end-of-life care. Good communication is paramount to determine patient and carer preferences for if, when, and how blood glucose monitoring should occur in the end-of-life setting. We present two differing cases of how continuous glucose monitoring in an Australian setting impacted end-of-life care for the patients and their carers.

Impact of Diabetes Status and Medication on Presentation, Treatment, and Outcome of Stage II Colon Cancer Patients.

Diabetes is a risk factor for colorectal cancer and several reports suggest worse cancer-specific outcomes in diabetes patients. Recent studies in multiple tumour types indicate metformin may positively impact on cancer-specific and overall survival. A population-based series of stage II colorectal cancer patients treated and followed from 2000 to 2013 were analysed for baseline characteristics, treatment, and outcomes. 1116 patients with stage II colon cancer were identified, 55.5% were male and median age was 70.9 years (range 20.5-101.2). The diabetes patients (21.6%, n = 241) were older than nondiabetes patients (median 74.0 versus 69.6, p = 0.0001). There was no impact of diabetes on cancer presentation or pathology. Diabetes patients were less likely to receive adjuvant treatment (13.7 versus 24.8%, p = 0.002) but were equally likely to complete treatment (69.7 versus 67.7%, p = 1.00). Diabetes did not significantly impact cancer recurrence (HR = 1.07, 95% CI 0.71-1.63) or overall survival (HR = 1.23, 95% CI 0.88-1.72), adjusted for age. Diabetes medication did not impact cancer recurrence or survival. Cancer presentation and outcomes in diabetes patients are comparable to those of nondiabetes patients in those with stage II colon cancer. The effect of metformin merits further evaluation in patients with colon cancer.

Lymphocytic hypophysitis in the elderly.

We report a 73-year-old woman with lymphocytic hypophysitis who presented with atypical clinical features and what appeared to be pituitary apoplexy on radiological analysis. Lymphocytic hypophysitis is a rare cause of pituitary dysfunction, and is thought to be an autoimmune disorder. It typically affects young peri-partum women, with clinical features that are related to pituitary hypofunction, and an uncertain natural history. It is difficult to radiologically differentiate lymphocytic hypophysitis from pituitary macroadenoma, therefore, the gold standard of diagnosis remains histological. It is rarely reported in the elderly (> 70 years old), however, given its unpredictable clinical course it remains an important differential diagnosis in patients of this age group who present with features suggestive of pituitary dysfunction.

Screening for new-onset diabetes after kidney transplantation: limitations of fasting glucose and advantages of afternoon glucose and glycated hemoglobin.

BACKGROUND: The sensitivity of fasting plasma glucose (FPG) in screening for new-onset diabetes after transplantation (NODAT) has been questioned, particularly in the presence of moderate-dose prednisolone, where peak plasma glucose occurs 7 to 8 hr after administration. Oral glucose tolerance testing (OGTT) has been mooted as an alternative but is inconvenient for patients. METHODS: We compared sensitivity of screening tests for NODAT at 6 weeks, 3 months, and 12 months after kidney transplantation in recipients receiving prednisolone, mycophenolate, and tacrolimus. RESULTS: At 6 weeks, NODAT (capillary blood glucose [CapBG] ≥11.1 mmol/L, FPG ≥7.0 mmol/L, 2-hr plasma glucose ≥11.1 mmol/L, or glycated hemoglobin [HbA1c] ≥6.5%) was detected in 46% with CapBG versus 12% with OGTT (P=0.013), 4% with HbA1c (P<0.001), and 0% with FPG (P<0.001; n=26). At 3 months, NODAT was present in 14% with HbA1c versus 20% with OGTT (P=0.600) and 2% with FPG (P=0.059; n=50), whereas, at 12 months, NODAT was found in 4% with HbA1c versus 6% with OGTT (P=1.00) and 2% with FPG (P=0.618; n=51). Combining 3- and 12-month data, OGTT recorded NODAT in 14% and impaired glucose tolerance in 28%, whereas HbA1c detected NODAT in 10% and impaired glucose tolerance (from ≥5.7 to <6.5%) in 51%. Employing HbA1c as a screening test and reserving OGTT for those with impaired glucose tolerance would detect NODAT with a sensitivity more than 94%, avoiding the need for OGTT in 49% of patients. CONCLUSIONS: This study confirms the inadequacy of FPG screening for NODAT in the first 6 weeks after transplantation, at which time 4 p.m. CapBG also outperformed OGTT. From 3 months, HbA1c had similar sensitivity to OGTT and represents a convenient alternative.

Advanced glycation end products are direct modulators of ß-cell function.

OBJECTIVE: Excess accumulation of advanced glycation end products (AGEs) contributes to aging and chronic diseases. We aimed to obtain evidence that exposure to AGEs plays a role in the development of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The effect of AGEs was examined on insulin secretion by MIN6N8 cells and mouse islets and in vivo in three separate rodent models: AGE-injected or high AGE-fed Sprague-Dawley rats and nonobese diabetic (NODLt) mice. Rodents were also treated with the AGE-lowering agent alagebrium. RESULTS: ß-Cells exposed to AGEs displayed acute glucose-stimulated insulin secretory defects, mitochondrial abnormalities including excess superoxide generation, a decline in ATP content, loss of MnSOD activity, reduced calcium flux, and increased glucose uptake, all of which were improved with alagebrium treatment or with MnSOD adenoviral overexpression. Isolated mouse islets exposed to AGEs had decreased glucose-stimulated insulin secretion, increased mitochondrial superoxide production, and depletion of ATP content, which were improved with alagebrium or with MnTBAP, an SOD mimetic. In rats, transient or chronic exposure to AGEs caused progressive insulin secretory defects, superoxide generation, and ß-cell death, ameliorated with alagebrium. NODLt mice had increased circulating AGEs in association with an increase in islet mitochondrial superoxide generation, which was prevented by alagebrium, which also reduced the incidence of autoimmune diabetes. Finally, at-risk children who progressed to T1D had higher AGE concentrations than matched nonprogressors. CONCLUSIONS: These findings demonstrate that AGEs directly cause insulin secretory defects, most likely by impairing mitochondrial function, which may contribute to the development of T1D.