BackgroundRecently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been shown to determine susceptibility to murine virus-induced diabetes. In addition, a previous human genome-wide study suggested the type 1 diabetes (T1D) susceptibility region to be 19p13, where the human TYK2 gene is located (19p13.2).MethodsPolymorphisms of TYK2 gene at the promoter region and exons were studied among 331 healthy controls, and 302 patients with T1D and 314 with type 2 diabetes (T2D) in the Japanese.FindingsA TYK2 promoter haplotype with multiple genetic polymorphisms, which are in complete linkage disequilibrium, named TYK2 promoter variant, presenting decreased promoter activity, is associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.6; P = 0.01), but also T2D (OR, 2.1; 95% CI, 1.1 to 4.1; P = 0.03). The risk is high in patients with T1D associated with flu-like syndrome at diabetes onset and also those without anti-glutamic acid decarboxylase autoantibody.InterpretationThe TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans.FundingMinistry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.

The aim of the present study was to investigate the prevalence of fear of hypoglycemia, in association with severe hypoglycemia and social factors, in insulin-treated patients with type 2 diabetes mellitus. A questionnaire survey on hypoglycemia and patient–physician communication was carried out in 355 patients with insulin-treated type 2 diabetes mellitus patients at 16 hospitals and clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise logistic regression analysis found that severe hypoglycemia during the past 1 year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95% confidence interval 1.06–4.41; P = 0.034), and age (odds ratio 1.02, 95% confidence interval 1.00–1.05, P = 0.038) and living alone (odds ratio 1.93, 95% confidence interval 1.00–3.73, P < 0.05) were significantly higher in patients with fear of hypoglycemia than in those without it.

Careful selection of patients based on high-resolution computed tomography findings and intraoperative pathologic exploration makes intentional limited resection an acceptable option for the treatment of small peripheral NSCLC.

Sixty-eight neonates with functional ileus were reviewed. Twelve required laparotomy; in seven, histological studies revealed decreased ganglia and ganglion cells of the myenteric plexus (MP) (Group A), and in five, MP was normal (Group B). In the remaining 56 cases, obstructive symptoms were relieved following conservative therapy (Group C). All Group A cases except one had normal birth weight, while Group B and C cases showed significantly lower birth weights. A marked caliber change of the small intestine and/or small-caliber distal intestine with meconium stagnation in the proximal intestine was commonly demonstrated at operation in Group A and B, or on contrast enema in Group C. Four Group A cases died of enteritis, and three survivors suffered from prolonged obstructive symptoms. The grade of histological abnormality of MP correlated with the clinical outcome. In Group B, three died of sepsis shortly after surgery, but two survivors have been free from symptoms. Group A can be categorized as Hirschsprung's disease-allied disorders (HAD). Group B and C can be categorized as meconium-related ileus (MRI). The similarity of the macroscopic findings of HAD and MRI, and the occurrence of MRI exclusively in low birth weight neonates, strongly suggest that functional immaturity of MP plays a role in the etiology of MRI.

A repeated heavy alcohol intake could increase the risk of hypertension for Japanese subjects who exhibit skin flushing in response to alcohol consumption. Chronic alcohol intake by subjects with alcohol flushing might bring about a significant increase in blood acetaldehyde levels and cause an additional rise in the blood pressure.