Young women with AN have low cold-activated BAT, which may be due to impaired BAT thermogenesis. Young women with BAT have higher BMD and lower Pref-1 compared with women without BAT, suggesting that BAT may be involved in the regulation of stem cell differentiation into the bone lineage at the expense of adipogenesis.
Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.
Objective
Despite a lack of data demonstrating benefit, psychotropic medications are frequently prescribed for patients with anorexia nervosa.
Method
We studied 525 women (18–54 years of age) with anorexia nervosa who presented to the Clinical Research Center at the Massachusetts General Hospital between January 1997–December 2009. For this analysis, participants were a priori divided into two groups based on date of presentation (group I: participants presenting between 1997–2002; group II: participants presenting between 2003–2009).
Results
Overall, 53% of participants reported current use of any psychotropic medication; 48.4% reported use of an antidepressant and 13% reported use of an antipsychotic. Twice as many participants in group II (18.5%) reported using atypical antipsychotics as compared to group I (8.9%) (p=0.002).
Discussion
A majority of participants with anorexia nervosa report using psychotropic medications despite lack of data supporting their efficacy. These data are concerning given the known adverse effects of these medications.
Context
Insulin autoimmune syndrome (IAS) is characterized by hyperinsulinemic hypoglycemia with elevated anti-insulin antibodies. Most commonly observed in the Japanese population, elsewhere it is rare and associated with autoimmune diseases, plasma cell dyscrasias, or sulfhydryl group medications. The active metabolite of clopidogrel has a sulfhydryl group and here we report a case of clopidogrel-induced IAS.
Case Description
A 67-year-old man was admitted with severe hyperinsulinemic hypoglycemia requiring continuous intravenous infusion of 10% dextrose to sustain euglycemia. His symptoms of hypoglycemia had started after commencing dual antiplatelet therapy (including clopidogrel) for ischemic heart disease 9 months earlier. The hypoglycemia was associated with elevated insulin, proinsulin, c-peptide, and anti-insulin antibody titers as well as the HLA-DRB1*04 haplotype. Multiple localizing studies were negative for an insulinoma. A diagnosis of IAS was thus made. Clopidogrel cessation, oral dexamethasone, and diazoxide therapy were not sufficient to safely wean the dextrose infusion. Plasma exchange was ultimately effective.
Conclusions
This case highlights a case of severe IAS. Given the ubiquity of clopidogrel, IAS should be remembered as a rare adverse effect.
We present a case of an obese 22-year-old man with activating GCK variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel GCK missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant. Glucokinase enables phosphorylation of glucose, the rate-limiting step of glycolysis in the liver and pancreatic β cells. It plays a crucial role in the regulation of insulin secretion. Inactivating variants in GCK cause hyperglycemia and activating variants cause hypoglycemia. Spleen-preserving distal pancreatectomy revealed diffuse hyperplastic islets, nuclear pleomorphism and periductular islets. Glucose stimulated insulin secretion revealed increased insulin secretion in response to glucose. Cytoplasmic calcium, which triggers exocytosis of insulin-containing granules, revealed normal basal but increased glucose-stimulated level. Unbiased gene expression analysis using 10X single cell sequencing revealed upregulated INS and CKB genes and downregulated DLK1 and NPY genes in β-cells. Further studies are required to see if alteration in expression of these genes plays a role in the metabolic and histological phenotype associated with glucokinase pathogenic variant. There were more large islets in the patient’s pancreas than in control subjects but there was no difference in the proportion of β cells in the islets. His hypoglycemia was persistent after pancreatectomy, was refractory to diazoxide and improved with pasireotide. This case highlights the variable phenotype of GCK mutations. In-depth molecular analyses in the islets have revealed possible mechanisms for hyperplastic islets and insulin hypersecretion.
Purpose
Anorexia nervosa (AN) is a psychiatric disorder characterized by restrictive eating, low body weight, and severe bone loss. Recent data show a deleterious relationship between low circulating sodium levels and bone mass, and relative or absolute hyponatremia is a known complication of AN. Clinical studies of other medical conditions associated with hyponatremia suggest that detrimental effects of low sodium levels on health are seen even within the normal range. We hypothesized that women with AN and relatively low sodium levels would have lower bone mineral density (BMD) than those with higher sodium levels.
Methods
In a cross-sectional study (1997–2009) of 404 women ages 17–54 (mean±SEM age 25.6±0.3 years) who met DSM-IV criteria for AN, we measured BMD using dual energy x-ray absorptiometry (DXA). BMD was compared in women with sodium levels <140 mmol/L (midpoint of normal range) vs. those with sodium levels ≥140 mmol/L, and in women with hyponatremia (sodium <135 mmol/L) vs. those without.
Results
Women with sodium levels <140 mmol/L had lower BMD, T- and Z-scores at the AP spine (Z-scores −1.6±0.1 vs. −1.3±0.1, p=0.004) and total hip (−1.2±0.1 vs. −0.9±0.1, p=0.029) vs. those with sodium levels ≥140 mmol/L. In a model including age, BMI, psychiatric drug use, and disease duration, differences remained significant at the AP spine. Hyponatremic women had lower BMD, T- and Z-scores at the AP spine (Z-scores −2.2±0.3 vs. −1.3±0.1, p=0.009), lateral spine (−2.4±0.4 vs. −1.5±0.1, p=0.031) and total hip (−2.5±0.5 vs. −1.0±0.1, p<0.0001) vs. those without. In a model including age, BMI, psychiatric drug use, and disease duration, differences remained significant at all sites.
Conclusions
These data suggest that relative sodium deficiency may contribute to AN-related osteopenia.
Aceruloplasminaemia is an autosomal recessive disorder of iron metabolism which is characterised by diabetes, neurodegeneration and anaemia. It should be considered in the differential diagnosis of adult onset, antibody-negative diabetes associated with persistent mild anaemia and hyperferritinaemia and/or progressive neuropsychiatric impairments.
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