Severe hyponatraemia with cerebral oedema after Pfizer BNT162b2 mRNA vaccination against COVID-19.

Background: Severe hyponatraemia can lead to serious neurological complications including coma, seizure and death. Hyponatraemia and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) has been previously described in cases of COVID-19, however there have been few reports post vaccination. We describe a case of severe hyponatraemia post second Pfizer BNT162b2 mRNA vaccination against COVID-19. Case presentation: A 48-year-old previously well woman presented to the emergency department with severe headaches and confusion one day after she received her second Pfizer COVID-19 vaccination. She reported no more than 2.5 L fluid intake. Vital signs were normal. Laboratory investigation revealed serum sodium 113 mmol/L, potassium 3.4 mmol/L, urea 3.5 mmol/L and serum osmolality 266 mmol/kg. TSH, random cortisol and C-reactive protein levels were normal. She was found to be in urinary retention and developed marked polyuria post in dwelling catheter insertion. Following this she underwent spontaneous and rapid correction of serum sodium without intervention. Retrospective analysis showed an inappropriately high copeptin of 4.4 pmol/L. Conclusions: It is important to be cautioned and aware of hyponatraemia as an immediate side effect of COVID-19 vaccination. The exact mechanism is unknown and further research is required to understand the acute endocrine effects which may arise in response to COVID-19 vaccination.

The relationship between diabetes and surgical site infection following coronary artery bypass graft surgery in current-era models of care.

BACKGROUND: Although diabetes is a recognized risk factor for postoperative infections, the seminal Portland Diabetic Project studies in cardiac surgery demonstrated intravenous insulin infusions following open-cardiac surgery achieved near normal glycaemia and decreased deep sternal wound infection to similar rates to those without diabetes. AIM: We sought to examine a contemporary cohort of patients undergoing coronary artery bypass graft surgery (CABGS) to evaluate the relationship between diabetes, hyperglycaemia and risk of surgical site infection (SSI) in current-era models of care. METHODS: Consecutive patients who underwent CABGS between 2016 and 2018 were identified through a state-wide data repository for healthcare-associated infections. Clinical characteristics and records of postoperative SSIs were obtained from individual chart review. Type 2 diabetes (T2D), perioperative glycaemia and other clinical characteristics were analysed in relation to the development of SSI. FINDINGS: Of the 953 patients evaluated, 11% developed SSIs a median eight days post CABGS, with few cases of deep SSIs (<1%). T2D was evident in 41% and more prevalent in those who developed SSIs (51%). On multivariate analysis T2D was not significantly associated with development of SSI (odds ratio (OR) 1.35; P=0.174) but body mass index (BMI) remained a significant risk factor (OR 1.07, P<0.001). In patients with T2D, perioperative glycaemia was not significantly associated with SSI. CONCLUSION: In a specialist cardiac surgery centre using perioperative intravenous insulin infusions and antibiotic prophylaxis, deep SSIs were uncommon; however, approximately one in 10 patients developed superficial SSIs. T2D was not independently associated with SSI yet BMI was independently associated with SSI post CABGS.

Diabetes associated with immune checkpoint inhibition: presentation and management challenges.

BACKGROUND: In recent years, immune checkpoint blockade has become a standard therapy for a wide range of cancers. Adverse events including endocrinopathies result from the induction of autoimmunity. CASE REPORT: We report a case series of nine individuals who presented with immunotherapy-induced type 1 diabetes between 2015-2017. DISCUSSION: Onset of diabetes occurred within 12 weeks of commencing therapy. Anti- GAD antibodies were present in six people. Retrospective testing of islet antibodies in pre-treatment samples was possible in two people and this revealed anti-GAD seroconversion in the first and high anti-GAD titres pre and post-treatment in the second person. Six people had high risk HLA haplotypes. Clinical and genetic factors are described and compared with previously published cases. This article is protected by copyright. All rights reserved.

Systemic mastocytosis identified in two women developing fragility fractures during lactation.

Two women presenting with fragility fractures during lactation had bone mineral density (BMD) reduced more greatly than usually associated with lactation. The first woman was 29 years old with a BMD T-score of - 3.2 SD at the spine and- 2.0 SD at the femoral neck. The second woman was 35 years old with a BMD T-score of - 4.5 SD at the spine and - 2.8 SD at the femoral neck. Both women had increased cortical porosity and reduced trabecular density. Investigation identified an elevated serum tryptase, and marrow biopsy confirmed the diagnosis of mastocytosis. Lactation causes bone loss, but the occurrence of fractures in the setting of severe deficits in BMD and microstructural deterioration signals the need to consider additional causes of bone loss.

Glucose alert system improves health professional responses to adverse glycaemia and reduces the number of hyperglycaemic episodes in non-critical care inpatients.

AIM: To investigate the effect of a novel glucose alert system, comprising the Melbourne Glucose Alert Pathway and glucose-alert-capable networked blood glucose meters, on nursing and hospital medical officer responses to adverse glycaemia. METHODS: A prospective, pre- and post-observational study was undertaken in non-critical care wards of a tertiary hospital over 4 months (n=148 or 660 patient-days). The intervention consisted of two components designed to promote a consistent staff response to blood glucose measurements: (1) a clinical escalation pathway, the Melbourne Glucose Alert Pathway, and (2) networked blood glucose meters, which provide a visual alert for out-of-range blood glucose measurement. All consecutive inpatients with diabetes were assessed for diabetes management and capillary blood glucose. The primary outcome was documented nursing and medical staff action in response to episodes of adverse glycaemia (blood glucose >15 mmol/l or <4 mmol/l). Secondary outcomes consisted of glycaemic measures. RESULTS: In response to episodes of adverse glycaemia, nursing action increased (proportion with nursing action: 45% to 73%; P<0.001), and medical action increased (proportion with medical action: 49% to 67%; P=0.011) with the glucose alert system in place. Patient-days with hyperglycaemia (any blood glucose value >15 mmol/l: 24% vs 16%; P=0.012) and patient-days with mean blood glucose >15 mmol/l (7.4% vs 2.6%; P=0.005) decreased. There was no difference in hypoglycaemia incidence. CONCLUSIONS: Use of a novel glucose alert system improved health professional responses to adverse glycaemia and decreased hyperglycaemia in the hospital setting.

Factors associated with insulin-induced weight gain in an Australian type 2 diabetes outpatient clinic.

BACKGROUND: Insulin-induced weight gain is a key concern for people with type 2 diabetes (T2D) and their treatment team. This study aimed to document the prevalence of insulin-induced weight gain and its impact on cardiovascular risk factors in patients attending the Royal Melbourne Hospital diabetes clinic. METHODS: Clinical and biochemical data were extracted from a prospective clinic database and from the hospital record. These variables were correlated with the percentage weight change 1 year after starting insulin and compared between groups with or without clinically significant weight gain, defined as more than 7% of the baseline bodyweight. RESULTS: The population comprised 340 patients (184 male), representing 36% of people with T2D who commenced insulin at our clinic. Their mean ± SD age and duration of diabetes was 63 ± 11 and 13 ± 8 years respectively. The mean (95% CI) change in bodyweight at 1 year was 3.0 (2.5-3.5) kg, but this was not associated with deleterious changes in blood pressure or lipid profile. Weight gain was associated with higher insulin doses, the use of short-acting insulin and with lower baseline bodyweight. Clinically significant weight gain occurred in 87 patients and was associated with glucose-lowering regimens that included short-acting insulin or a thiazolidinedione, whereas regimens that incorporated other oral agents, particularly sulfonylureas, were associated with less weight gain. CONCLUSION: In this Australian tertiary hospital population with T2D, insulin-induced weight gain was common but was not associated with deleterious changes in blood pressure or lipids. Treatment regimens that avoid short-acting insulin but include oral agents other than thiazolidinediones might prevent insulin-induced weight gain in T2D.

Higher body mass index in adults at diagnosis of the slowly progressive form of type 1 diabetes mellitus is associated with lower risk HLA genes.

We hypothesised that higher body weight, a proposed risk factor for type 1 diabetes mellitus, would be associated with increased penetrance of lower risk genes. In adults at diagnosis of the slowly progressive form of type 1 diabetes mellitus we found that higher body mass index was associated with the absence of the highest risk HLA genes.

New-onset diabetes after kidney transplantation-changes and challenges.

Despite substantial improvement in short-term results after kidney transplantation, increases in long-term graft survival have been modest. A significant impediment has been the morbidity and mortality attributable to cardiovascular disease (CVD). New-onset diabetes after transplantation (NODAT) is an independent predictor of cardiovascular events. This review examines recent literature surrounding diagnosis, outcomes and management of NODAT. Amongst otherwise heterogeneous studies, a common finding is the relative insensitivity of fasting blood glucose (FBG) as a screening test. Incorporating self-testing of afternoon capillary BG and glycohemoglobin (HbA(1c) ) detects many cases that would otherwise remain undetected without the oral glucose tolerance test (OGTT). Assessing the impact of NODAT on patient and graft survival is complicated by changes to diagnostic criteria, evolution of immunosuppressive regimens and increasing attention to cardiovascular risk management. Although recent studies reinforce a link between NODAT and death with a functioning graft (DWFG), there seems to be little effect on death-censored graft loss. The significance of glycemic control and diabetes resolution for patient outcomes remain notably absent from NODAT literature and treatment is also a neglected area. This review examines new and old therapeutic options, emphasizing the need to assess ß-cell pathology in customizing therapy. Finally, areas warranting further research are considered.

Oral vitamin D replacement is effective in chronic liver disease.

BACKGROUND & AIMS: End-stage chronic liver disease is associated with vitamin D deficiency but the prevalence across a broad-spectrum of liver disease is unknown. This study prospectively examines prevalence of vitamin D deficiency and response to replacement in chronic liver disease. METHODS: One hundred and fifty-eight outpatients with chronic liver disease were enrolled. Serum 25-hydroxyvitamin D (25[OH]D) levels were classified as: severely deficient less than 25 nmol/l, deficient 25-54 nmol/l or replete greater than 54 nmol/l. Sixty-five of 158 (41%) had cirrhosis. RESULTS: 25[OH]D was suboptimal in 101/158 (64%), including severe deficiency in 24 patients (15%). Vitamin D deficiency occurred in liver disease of all aetiologies, including patients with only mild liver disease. 25[OH]D increased by 60.0% (19.11 ± 13.20 nmol/l) in patients with deficiency after vitamin D replacement and decreased by 25.2% (-18.33 ± 12.02 nmol/l) in non-treated initially replete patients over a median of 4 months. CONCLUSIONS: Vitamin D deficiency improves with oral vitamin D supplementation and levels fall without supplementation. Chronic liver disease patients are at very high risk of vitamin D deficiency regardless of etiology or severity.

Latent autoimmune diabetes in adults (LADA) should be less latent.

'Latent autoimmune diabetes in adults' (LADA) is the term coined to describe adults who have a slowly progressive form of autoimmune or type 1 diabetes that can be treated initially without insulin injections. The diagnosis of LADA is currently based on three clinical criteria: (1) adult age at onset of diabetes; (2) the presence of circulating islet autoantibodies, which distinguishes LADA from type 2 diabetes; and (3) insulin independence at diagnosis, which distinguishes LADA from classic type 1 diabetes. The prevalence of LADA in adults presenting with non-insulin-requiring diabetes is approximately 10%. Recognition of LADA expands the concept and prevalence of autoimmune diabetes, but LADA remains poorly understood at both a clinical and research level. In this perspective, we review the nomenclature, diagnostic criteria, genetics, pathology and therapy of LADA, to arrive at recommendations that might advance knowledge and management of this form of diabetes.

Insulin resistance is a risk factor for progression to type 1 diabetes.

AIMS/HYPOTHESIS: Glucose homeostasis is determined by an interplay between insulin secretion and insulin action. In type 1 diabetes, autoimmune destruction of pancreatic beta cells leads to impaired insulin secretion. However, the contribution of impaired insulin action (insulin resistance) to the development of type 1 diabetes has received little attention. We investigated whether insulin resistance was a risk factor for progression to type 1 diabetes. METHODS: Islet-antibody-positive first-degree relatives of type 1 diabetes probands were followed for 4.0 years (median). Insulin secretion was measured as first-phase insulin response (FPIR) to intravenous glucose. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-R). We compared subjects who progressed (n=43) and subjects who did not progress (n=61) to diabetes, including 21 pairs matched for age, sex, islet antibodies and FPIR. RESULTS: Progressors had higher insulin resistance relative to insulin secretion at baseline (median HOMA-R : FPIR 0.033 vs 0.013, p<0.0001). According to Cox proportional hazards analysis, islet antibody number, FPIR, fasting plasma glucose, fasting serum insulin, HOMA-R and log(HOMA-R : FPIR) were each predictive of progression to diabetes. However, log(HOMA-R : FPIR) (hazard ratio 2.57 per doubling, p<0.001) was the only metabolic variable independently associated with progression. In the matched comparison, progressors had higher fasting glucose, fasting insulin, HOMA-R and HOMA-R : FPIR, both at baseline and during the follow-up pre-clinical phase. CONCLUSIONS/INTERPRETATION: Relatives positive for islet antibodies who progress most rapidly to diabetes have a subtle disturbance of insulin-glucose homeostasis years before the onset of symptoms, distinguished by greater insulin resistance for their level of insulin secretion. Taking steps to reduce this insulin resistance could therefore delay the development of type 1 diabetes.