Cut-Off Value of Total Adiponectin

Aim To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. Methods A total of 365 subjects without MetS aged 20–60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. Results During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0–6.6, 6.7–8.8 and ≥ 8.9 μg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02–0.78; P = 0.03) in subjects with total adiponectin level of 5.0–6.6 μg/ml, and 0.15 (95% CI 0.02–0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 μg/ml compared with those with total adiponectin level ≥ 8.9 μg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 μg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 μg/ml compared with > 6.2 μg/ml (TR 0.22, 95% CI: 0.08–0.64, P = 0.005). Conclusion Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 μg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 μg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 μg/ml

Case Report Asymptomatic Congenital Hyperinsulinism due to a Glucokinase-Activating Mutation, Treated as Adrenal Insufficiency for Twelve Years

Congenital hyperinsulinism (CHI) caused by a glucokinase-(GCK-) activating mutation shows autosomal dominant inheritance, and its severity ranges from mild to severe. A 43-year-old female with asymptomatic hypoglycemia (47 mg/dL) was diagnosed as partial adrenal insufficiency and the administration of hydrocortisone (10 mg/day) was initiated. Twelve years later, her 8-monthold grandchild was diagnosed with CHI. Heterozygosity of exon 6 c.590T>C (p.M197T) was identified in a gene analysis of GCK, which was also detected in her son and herself. The identification of GCK-activating mutations in hyperinsulinemic hypoglycemia patients may be useful for a deeper understanding of the pathophysiology involved and preventing unnecessary glucocorticoid therapy

Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia

Background Parthenogenetic mosaicism is an extremely rare condition identified only in five subjects to date. The previous studies indicate that this condition is mediated by parthenogenetic activation and is free from a specific phenotype ascribed to unmaking of a maternally inherited recessive variant in the parthenogenetic cell lineage. Results We examined a 28-year-old Japanese 46,XX female with Silver-Russell syndrome and idiopathic hypersomnia. The results revealed (1) predominance of maternally derived alleles for all the differentially methylated regions examined; (2) no disease-related copy-number variant; (3) two types of regions for all chromosomes, i.e., four BAF (B-allele frequency) band regions with single major microsatellite peaks of maternal origin and single minor microsatellite peaks of non-maternal (paternal) origin, and six BAF band regions with single major microsatellite peaks of maternal origin and two minor microsatellite peaks of maternal and non-maternal (paternal) origin; (4) an unmasked extremely rare PER2 variant (c.1403G>A:p.(Arg468Gln)) with high predicted pathogenicity; (5) mildly affected local structure with altered hydrogen bonds of the p.Arg468Gln-PER2 protein; and (6) nucleus-dominant subcellular distribution of the p.Arg468Gln-PER2 protein. Conclusions The above findings imply that the second polar body retention occurred around fertilization, resulting in the generation of the parthenogenetic cell lineage by endoreplication of a female pronucleus and the normal cell lineage by fusion of male and female pronuclei, and that the homozygous PER2 variant in the parthenogenetic cells is the likely causative factor for idiopathic hypersomnia

NFκBとMAPKシグナルを介した炎症増強における前駆脂肪細胞内グルココルチコイド再活性化の意義

京都大学0048新制・課程博士博士(医学)甲第15640号医博第3499号新制||医||983(附属図書館)28177京都大学大学院医学研究科内科系専攻(主査)教授 稲垣 暢也, 教授 成宮 周, 教授 長田 重一学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Asymptomatic Congenital Hyperinsulinism due to a Glucokinase-Activating Mutation, Treated as Adrenal Insufficiency for Twelve Years

Congenital hyperinsulinism (CHI) caused by a glucokinase- (GCK-) activating mutation shows autosomal dominant inheritance, and its severity ranges from mild to severe. A 43-year-old female with asymptomatic hypoglycemia (47 mg/dL) was diagnosed as partial adrenal insufficiency and the administration of hydrocortisone (10 mg/day) was initiated. Twelve years later, her 8-month-old grandchild was diagnosed with CHI. Heterozygosity of exon 6 c.590T>C (p.M197T) was identified in a gene analysis of GCK, which was also detected in her son and herself. The identification of GCK-activating mutations in hyperinsulinemic hypoglycemia patients may be useful for a deeper understanding of the pathophysiology involved and preventing unnecessary glucocorticoid therapy

Novel germline variant of TMEM127 gene in a patient with familial pheochromocytoma

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumours with a heterogeneous genetic background. Up to 40% of apparently sporadic PCC/PGL cases carry 1 of the 12 gene germline mutations conferring genetic susceptibility to PCC/PGL. Although the precise mechanisms are unclear, TMEM127 is one of the rare responsible genes for PCC/PGL. Here we report the case of a patient with familial PCC having a novel TMEM127 variant (c.119C > T, p.S40F). In silico prediction analysis to evaluate the functional significance of this variant suggested that it is a disease-causing variant. A PCC on the left side was considered to be the dominant lesion, and unilateral adrenalectomy was performed. The histopathologic findings were consistent with benign PCC. A loss of heterogeneity of the TMEM127 variant was detected in the surgically removed tumour

Cut-off values of total adiponectin level for managing risk of developing MetS according to top five log likelihoods in each survival distribution.

<p>Cut-off values were confined to top five log likelihoods in each survival distribution.</p><p>* Comparison was made between subjects with total adiponectin level ≤ cut-off value and subjects with total adiponectin level > cut-off value.</p><p>Multivariate adjustment was performed for age, BMI, smoking habit, alcohol intake, and regular exercise.</p><p>MetS, metabolic syndrome; AIC, Akaike’s information criterion</p><p>Cut-off values of total adiponectin level for managing risk of developing MetS according to top five log likelihoods in each survival distribution.</p

TR and 95% CI for development of MetS according to total adiponectin level at baseline based on Weibull distribution.

<p>Multivariate adjustment was performed for age, BMI, smoking habit, alcohol intake, and regular exercise.</p><p>MetS, metabolic syndrome; TR, time ratio</p><p>TR and 95% CI for development of MetS according to total adiponectin level at baseline based on Weibull distribution.</p