Short-term hyperglycemic dysregulation in patients with type 1 diabetes does not change myocardial triglyceride content or myocardial function.

OBJECTIVE: To evaluate the effects of hyperglycemia due to partial insulin deprivation on myocardial triglyceride (TG) content and myocardial function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Myocardial and hepatic TG content and left ventricular (LV) function were measured by magnetic resonance (MR) spectroscopy and MR imaging during optimal glucoregulation and after 24 h of partial insulin deprivation (n = 10). RESULTS: Mean insulin infusion rate was 45 +/- 5 units at baseline, whereas it was 27 +/- 5 units during hyperglycemia (per 24 h, P < 0.001). Plasma glucose levels increased from 8.4 +/- 0.6 to 15.9 +/- 0.8 mmol/l (P < 0.001), and plasma levels of nonesterified fatty acids from 0.31 +/- 0.05 to 0.46 +/- 0.07 mmol/l (P = 0.015). Hyperglycemia had no effects on myocardial or hepatic TG content and LV function. CONCLUSIONS: Short-term hyperglycemic dysregulation does not modulate myocardial or hepatic TG content or myocardial function, despite considerable metabolic adaptations.

An autosomal dominant high bone mass phenotype in association with craniosynostosis in an extended family is caused by an LRP5 missense mutation.

Gain-of-function mutations in LRP5 have been shown to cause high BMD disorders showing variable expression of some clinical symptoms, including torus palatinus and neurological complications. In an extended family, we were able to add craniosynostosis and developmental delay to the clinical spectrum associated with LRP5 mutations. We report on an extended four-generation family with 13 affected individuals (7 men and 6 women) in which an autosomal dominant type of osteosclerosis segregates. Osteosclerosis was most pronounced in the cranial base and calvarium, starting in early childhood with variable expression and a progressive character. Craniosynostosis at an early age was reported in four affected family members (two males and two females). The patients also presented with dysmorphic features (macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones, prominent jaw). They have normal height and proportions. Neurological complications like entrapment of cranial nerves resulting in optical nerve atrophy, hearing loss, and facial palsy were reported in two individuals. A mild developmental delay was reported in three affected individuals. None of the patients have torus palatinus, increased rate of fractures, osteomyelitis, hepatosplenomegaly, or pancytopenia. A missense mutation 640G-->A (A214T) in the low-density lipoprotein receptor-related protein 5 (LRP5) gene was found in all affected individuals analyzed, including cases in whom craniosynostosis, a mild developmental delay, and/or macrocephaly is observed. To our knowledge, this is the first report in the literature of patients presenting with autosomal dominant osteosclerosis in whom a variable expression of craniosynostosis, macrocephaly, and mild developmental delay is observed, which is most likely associated with a mutation in the LRP5 gene. These phenotypes can therefore be added to the clinical spectrum of LRP5-associated bone disorders.

Atypical MEN type 2B associated with two germline RET mutations on the same allele not involving codon 918.

A kindred was diagnosed with atypical MEN type 2B characterized by medullary thyroid cancer and mucosal neurilemmomas in multiple family members. Mutation analysis revealed a double RET germline mutation, Val804Met and Ser904Cys, in affected individuals. The clinical phenotype, the functional effect of the mutations, and the clinical implications of our findings are discussed.