Insulinoma Presenting With Postprandial Hypoglycemia in a Pregnant Woman With MEN-1.

Insulinomas are rare insulin-secreting tumors of pancreatic origin that cause hypoglycemia and can be associated with multiple endocrine neoplasia type 1 (MEN1). While rare, they are the most common cause of hypoglycemia related to endogenous hyperinsulinism. A 28-year-old woman with known MEN1 presented with postprandial hypoglycemia in the second trimester of pregnancy. Prior to her presentation she was known to have several pancreatic neuroendocrine tumors that had been stable on serial imaging, but no history of hypoglycemia. She was managed with dietary intervention during pregnancy and gave birth to a healthy baby at 37 weeks' gestation. After pregnancy, hypoglycemia initially resolved, but then recurred at 8 months post partum. Magnetic resonance imaging showed several pancreatic neoplasms with the largest lesion measuring 29 mm in the pancreatic tail, unchanged from previous imaging. After localization with a selective arterial calcium stimulation test, the patient underwent successful distal pancreatectomy with resolution of symptoms. This case is unusual in that her initial presentation was during pregnancy, she had predominantly postprandial rather than fasting hypoglycemia, and her symptoms remitted for several months after delivery. Key learning points are to have a low index of suspicion for an insulinoma when there is a history of MEN1 and the need for a pragmatic approach to diagnosis and treatment during pregnancy.

Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study.

AIMS: To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM). METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbA1C ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA1C , fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. RESULTS: Postpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p < 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbA1C compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. CONCLUSIONS: Given very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.

The prevalence of diabetes distress and its association with glycaemia in young people living with insulin-requiring-diabetes in a regional centre in Australia.

AIM: Emotional responses, such as feeling overwhelmed with diabetes-related treatment, burnt-out and anxiety, are known as 'diabetes distress'. This study aimed to determine diabetes distress among children, adolescents and parents/carers managing insulin-requiring diabetes in a regional Australian setting, and to assess association with glycaemia. METHODS: All children, adolescents and their parents/carers attending a regional hospital outpatient diabetes clinic between March 2018 and June 2019 were invited to complete a validated child, adolescent or parent/carer diabetes distress questionnaire. Demographics and time-matched clinical data were obtained from hospital records. A cross-sectional analysis was performed. RESULTS: A total of 43 young people and 30 parents/carers completed a diabetes distress questionnaire during the study period. Diabetes distress was common, with 63% of young people and 67% of parents/carers nominating at least one serious concern. After adjustment for potential confounding factors, higher glycaemia (HbA1c %) was associated with higher distress scores among both young people (ß 6.2, 95% confidence interval (CI): 3.2-9.2, P < 0.001) and carers/parents (ß 5.6, 95% CI:1.5-9.8, P < 0.001). Diabetes distress did not differ by child age, duration of diagnosis or mode of insulin administration. For children, adolescents and carers, 'serious concerns' most commonly related to the impact of diabetes upon family and peer relationships. CONCLUSIONS: Diabetes distress was common and associated with sub-optimal glycaemia. Routine screening for diabetes distress should be considered in paediatric services. Development of strategies to minimise diabetes distress for youth and families is required.

Type 2 diabetes after a pregnancy with gestational diabetes among first nations women in Australia: The PANDORA study.

AIMS: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. RESULTS: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). CONCLUSIONS: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications.

Incorporating Aboriginal women's voices in improving care and reducing risk for women with diabetes in pregnancy - A phenomenological study.

BACKGROUND: There is a high burden of gestational diabetes (GDM) and type 2 diabetes in pregnancy for Aboriginal and Torres Strait Islander women. Postpartum diabetes programs have the potential to prevent recurrent GDM and improve management of type 2 diabetes. However, data on such programs are limited, particularly in the Indigenous context. We aimed to explore Aboriginal Australian women's and health providers' preferences for a program to prevent and improve diabetes after pregnancy. METHODS: A phenomenological methodology underpinned semi-structured in-depth interviews with eleven Aboriginal women and seven health professionals across the Northern Territory from October 2019- February 2020. Interviews were analysed using an inductive analysis framework to address the barriers and enablers of proposed diabetes prevention programs identified by participants. RESULTS: Identified structural barriers to lifestyle change included: food insecurity, persuasive marketing of unhealthy food options, lack of facilities and cultural inappropriateness of previous programs. Enablers to lifestyle change included: a strong link between a healthy lifestyle and connection with Country, family and community. Suggested strategies to improve lifestyle included: co-designed cooking classes or a community kitchen, team sports and structural change (targeting the social determinants of health). Lifestyle change was preferred over metformin to prevent and manage diabetes after pregnancy by participants and health care providers. CONCLUSIONS: We recommend individual level programs be designed alongside policies that address systemic inequalities. A postpartum lifestyle program should be co-designed with community members and grounded in Aboriginal conceptions of health to adequality address the health disparities experienced by Aboriginal people in remote communities.

Biparental contributions of the H2A.B histone variant control embryonic development in mice.

Histone variants expand chromatin functions in eukaryote genomes. H2A.B genes are testis-expressed short histone H2A variants that arose in placental mammals. Their biological functions remain largely unknown. To investigate their function, we generated a knockout (KO) model that disrupts all 3 H2A.B genes in mice. We show that H2A.B KO males have globally altered chromatin structure in postmeiotic germ cells. Yet, they do not show impaired spermatogenesis or testis function. Instead, we find that H2A.B plays a crucial role postfertilization. Crosses between H2A.B KO males and females yield embryos with lower viability and reduced size. Using a series of genetic crosses that separate parental and zygotic contributions, we show that the H2A.B status of both the father and mother, but not of the zygote, affects embryonic viability and growth during gestation. We conclude that H2A.B is a novel parental-effect gene, establishing a role for short H2A histone variants in mammalian development. We posit that parental antagonism over embryonic growth drove the origin and ongoing diversification of short histone H2A variants in placental mammals.

Diabetic ketoacidosis in acromegaly; a rare complication precipitated by corticosteroid use.

Diabetic ketoacidosis has been described in the literature as a rare possible initial presentation of acromegaly before a diagnosis of acromegaly is eventually made. Indeed, diabetic ketoacidosis is a recognised complication of acromegaly. There are a number of factors that can predispose patients with acromegaly to diabetes as well as to diabetic ketoacidosis. These include high levels of growth hormone and insulin-like growth factor 1 in acromegaly and the effect on glycaemia by medications used in the management of acromegaly. Ketoacidosis has been described in patients with acromegaly even without the presence of an underlying autoimmune diabetes. Patients with acromegaly and ketoacidosis often respond to treatment and may not require long-term insulin.

Corrigendum: Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols.

[This corrects the article on p. 106 in vol. 8, PMID: 28659865.].

Review of Evidence for Adult Diabetic Ketoacidosis Management Protocols.

BACKGROUND: Diabetic ketoacidosis (DKA) is an endocrine emergency with associated risk of morbidity and mortality. Despite this, DKA management lacks strong evidence due to the absence of large randomised controlled trials (RCTs). OBJECTIVE: To review existing studies investigating inpatient DKA management in adults, focusing on intravenous (IV) fluids; insulin administration; potassium, bicarbonate, and phosphate replacement; and DKA management protocols and impact of DKA resolution rates on outcomes. METHODS: Ovid Medline searches were conducted with limits "all adult" and published between "1973 to current" applied. National consensus statements were also reviewed. Eligibility was determined by two reviewers' assessment of title, abstract, and availability. RESULTS: A total of 85 eligible articles published between 1973 and 2016 were reviewed. The salient findings were (i) Crystalloids are favoured over colloids though evidence is lacking. The preferred crystalloid and hydration rates remain contentious. (ii) IV infusion of regular human insulin is preferred over the subcutaneous route or rapid acting insulin analogues. Administering an initial IV insulin bolus before low-dose insulin infusions obviates the need for supplemental insulin. Consensus-statements recommend fixed weight-based over "sliding scale" insulin infusions although evidence is weak. (iii) Potassium replacement is imperative although no trials compare replacement rates. (iv) Bicarbonate replacement offers no benefit in DKA with pH > 6.9. In severe metabolic acidosis with pH < 6.9, there is lack of both data and consensus regarding bicarbonate administration. (v) There is no evidence that phosphate replacement offers outcome benefits. Guidelines consider replacement appropriate in patients with cardiac dysfunction, anaemia, respiratory depression, or phosphate levels <0.32 mmol/L. (vi) Upon resolution of DKA, subcutaneous insulin is recommended with IV insulin infusions ceased with an overlap of 1-2 h. (vii) DKA resolution rates are often used as end points in studies, despite a lack of evidence that rapid resolution improves outcome. (viii) Implementation of DKA protocols lacks strong evidence for adherence but may lead to improved clinical outcomes. CONCLUSION: There are major deficiencies in evidence for optimal management of DKA. Current practice is guided by weak evidence and consensus opinion. All aspects of DKA management require RCTs to affirm or redirect management and formulate consensus evidence-based practice to improve patient outcomes.

Estimating glomerular filtration rate: Performance of the CKD-EPI equation over time in patients with type 2 diabetes.

AIMS: To assess the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and longitudinally in people with type 2 diabetes. METHODS: Adults with type 2 diabetes attending Austin Health, Melbourne, with≥3 prospective GFR measurements were included in this retrospective study. Plasma disappearance rate of DTPA (diethylene-triamine-penta-acetic acid) was used to calculate measured GFR (mGFR) and compared to estimated GFR (eGFR). The agreement between mGFR and eGFR was estimated using Intraclass Correlation Coefficient (ICC). RESULTS: 152 patients had a median of 4 (IQR: 3, 5) mGFR measurements over a period of 11years (IQR: 9, 12). The difference between mGFR and eGFR increased proportionally to the magnitude of the GFR, increasing by 0.2ml/min/1.73m(2) for every 1ml/min/1.73m(2) increase in mGFR, indicative of proportional bias. At lower mGFR levels, eGFR overestimated mGFR, and at higher mGFR levels, eGFR underestimated mGFR. There was a significant association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR. CONCLUSIONS: The CKD-EPI formula underestimates mGFR and the rate of decline of mGFR in patients with type 2 diabetes with an mGFR greater than 60ml/min/1.73m(2). The association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR warrants further study.

Neonatal length inaccuracies in clinical practice and related percentile discrepancies detected by a simple length-board.

AIM: The study aims to assess accuracy of standard practice measurement of neonatal length compared with a gold-standard length-board technique. METHODS: Data were obtained from a population-based, cross-sectional study of 602 term babies at Royal Prince Alfred Hospital, Sydney, Australia, in 2010. Neonatal length was measured by standard clinical practice and by a length-board (gold standard) and measurements compared. Standard growth curve percentiles were used to plot length measurements. The Bland and Altman method was used to assess agreement, and acceptable levels of agreement were set at ≤1 cm and ≤0.5 cm. RESULTS: The limits of agreement were between -3.06 cm (95% CI -3.08 to -3.04) and 2.67 cm (95% CI 2.65 to 2.69). Neonates whose standard-practice length fell within 0.5 cm of the gold standard totalled 41% (241 neonates), while 59% (342) were >0.5 cm. The change in length resulted in a change in the percentile range of 53% (309) on a standard growth curve percentile. When examining neonates whose length was plotted at the extremes of percentile regions, the positive predictive value results of the standard practice compared with the gold standard were poor, with positive predictive values of 37.5%, 57.1% and 31.3% for neonates who were measured as <3rd, <10th and ≥90th percentile, respectively. CONCLUSIONS: In current clinical practice, measures of neonatal length are often inaccurate, which has implications for potentially erroneous clinical care. Health-care providers should be educated on the importance of length and trained in how to measure length with the correct technique using a length-board.