A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

Free Insulin-like Growth Factor (IGF)-I in Children with PWS.

In children with Prader−Willi syndrome (PWS), the standard growth hormone (GH) dose often results in high immunoreactive IGF-I levels. These high immunoreactive IGF-I levels lead to concern because their long-term effects are unknown. As a result, clinicians have to lower the GH dose, which worsens body composition and quality of life. As clinical features do not seem to correspond to immunoreactive IGF-I values, it is questionable whether immunoreactive IGF-I is a suitable marker for GH dosing, or whether another parameter better reflects IGF-I bioavailability and bioactivity. We, therefore, investigate serum immunoreactive IGF-I, free IGF-I and IGFBP-3 levels in 70 GH-treated children with PWS. Our study showed that, although immunoreactive IGF-I levels were high (>2 SDS) in the vast majority of prepubertal and pubertal children, free IGF-I SDS levels were <0 SDS in most and <1 SDS in all. Free IGF-I correlated with the immunoreactive IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio. We conclude that there is a major discrepancy between immunoreactive and free IGF-I levels. While in the majority of GH-treated children with PWS, immunoreactive IGF-I levels were high, free IGF-I levels were <0 SDS in most. Our data appear to be very reassuring and suggest that free IGF-I levels should also be taken into consideration when the immunoreactive IGF-I levels are >2 SDS in GH-treated children with PWS.

Increased Visceral Adipose Tissue and Hyperinsulinemia Raise the Risk for Recurrence of Non-B Non-C Hepatocellular Carcinoma after Curative Treatment.

We investigated the factors affecting recurrence-free survival in patients with non-B non-C hepatocellular carcinoma (HCC) who received curative treatment. Decision-tree analysis was performed in 72 curative cases of non-B non-C HCC to extract the risk factors for recurrence. The reliability of the extracted risk factors was evaluated using the Kaplan-Meier method and the Cox proportional hazards model. The decision-tree analysis extracted three factors-visceral adipose tissue (VAT) index (VATI; <71 and ≥71 cm2/m2), which was the cross-sectional areas of VAT on the computed tomographic image at the umbilical level, normalized by the square of the height, fasting immunoreactive insulin (FIRI; <5.5 and ≥5.5 µU/mL), and alpha-fetoprotein (AFP; <11 and ≥11 ng/mL). The Cox proportional hazards model showed that VATI (hazard ratio (HR): 2.556, 95% confidence interval (CI): 1.191-5.486, p = 0.016), FIRI (HR: 3.149, 95% CI: 1.156-8.575, p = 0.025), and AFP (HR: 3.362, 95% CI: 1.550-7.288, p = 0.002) were all independent risk factors for HCC recurrence. Non-B non-C HCC patients with a higher VATI (≥71 cm2/m2) or higher FIRI (≥5.5 µU/mL) and AFP (≥11 ng/mL) if VATI was <71 cm2/m2 are prone to recurrence after curative treatment.

Improvement of glycemic control by treatment for insomnia with suvorexant in type 2 diabetes mellitus.

INTRODUCTION: Acute and chronic insomnia can exacerbate type 2 diabetes mellitus (T2DM). We investigated suvorexant (an anti-insomnia drug that targets the orexin system) effects on sleep architecture and glucose metabolism in T2DM patients with insomnia. MATERIALS AND METHODS: This 7 day open-label, single-arm, intervention trial included 18 subjects with T2DM and insomnia. After 1 day acclimatization, daily glucose levels, sleep architecture, and autonomic nervous function were evaluated by continuous glucose monitoring (CGM), single-channel electroencephalography, and accelerometry, respectively. RESULTS: Suvorexant treatment for 3 days significantly increased total sleep time and sleep efficiency, with partial suppression of sympathetic nerve activity. CGM-measured 24 h mean glucose level decreased significantly from 157.7 ±â€¯22.9 to 152.3 ±â€¯17.8 mg/dL, especially in the early glucose surge after the midnight nadir (from 28.3 ±â€¯15.0 to 18.2 ±â€¯9.9 mg/dL), and until supper with a significant improvement in homeostasis model assessment of insulin resistance from 4.0 ±â€¯2.8 to 2.9 ±â€¯1.6, respectively. CONCLUSIONS: Suvorexant treatment for insomnia of subjects with T2DM significantly improved CGM-measured daily glycemic control, which was associated with changes in sympathomimetic tone and/or improved insulin sensitivity. The amelioration of insomnia may therefore be a target for improving glycemic control in T2DM patients with insomnia.

Association of genetic variants of the incretin-related genes with quantitative traits and occurrence of type 2 diabetes in Japanese.

BACKGROUND: None of the high frequency variants of the incretin-related genes has been found by genome-wide association study (GWAS) for association with occurrence of type 2 diabetes in Japanese. However, low frequency and rare and/or high frequency variants affecting glucose metabolic traits remain to be investigated. METHOD: We screened all exons of the incretin-related genes (GCG, GLP1R, DPP4, PCSK1, GIP, and GIPR) in 96 patients with type 2 diabetes and investigated for association of genetic variants of these genes with quantitative metabolic traits upon test meal with 38 young healthy volunteers and with the occurrence of type 2 diabetes in Japanese subjects comprising 1303 patients with type 2 diabetes and 1014 controls. RESULT: Two mutations of GIPR, p.Thr3Alafsx21 and Arg183Gln, were found only in patients with type 2 diabetes, and both of them were treated with insulin. Of ten tagSNPs, we found that risk allele C of SNP393 (rs6235) of PCSK1 was nominally associated with higher fasting insulin and HOMA-R (P = 0.034 and P = 0.030), but not with proinsulin level, incretin level or BMI. The variant showed significant association with occurrence of type 2 diabetes after adjustment for age, sex, and BMI (P = 0.0043). CONCLUSION: Rare variants of GIPR may contribute to the development of type 2 diabetes, possibly through insulin secretory defects. Furthermore, the genetic variant of PCSK1 might influence glucose homeostasis by altered insulin resistance independently of BMI, incretin level or proinsulin conversion, and may be associated with the occurrence of type 2 diabetes in Japanese.

Analysis of relationship between stress hyperglycemia and variation of serum insulin in critical ill children / 中华实用儿科临床杂志

Objective To study the relationships between the level of blood glucose in critical ill children with the degree of critical illness and the variation of immunoreactive insulin (IRI) and true insulin (TI).Methods Fiftyeight children form the Neonatal Intensive Care Unit (PICU) and Department of Respiration were enrolled in this study.The children were divided into PICU group (42 cases) and control group (16 cases).The PICU group were scored pediatric critical score in 24 hours after admission.The 42 critical ill children were divided into stress hyperglycemia group (20 cases) and non-stress hyperglycemia group (22 cases) according to their blood glucose levels.The IRI,TI,C-Peptide and blood glucose were measured.Results The pediatric critical illness score of stress hyperglycemia group [(74.80 ± 8.07) scores] was significantly lower than that of non-stress hyperglycemia group [(84.36 ±9.46) scores] (t =1.964,P ＜ 0.05).The death rate of stress hyperglycemia group (45.0％,9/20 cases) was significantly higher than that of non-stress hyperglycemia group (13.6％,3/22 cases) (x2 =5.05,P ＜ 0.05).The IRI,TI and C-Peptide of stress hyperglycemia group were significantly higher than those of non-stress hyperglycemia group and control group(F =136.90,61.25,45.89,all P ＜ 0.05).The TI/IRI of stress hyperglycemia group was significantly lower than that of non-stress hyperglycemia group and control group (F =27.64,P ＜ 0.05).The TI,IRI and C-Peptide of stress hyperglycemia group were higher than after admission (t =2.241,2.087,2.014,all P ＜ 0.05).Conclusions The children with critical illness have stress hyperglycemia and the component of insulin is changed,and the absolute level as well as the rate of TI and TI/IRI are descended.

First-phase insulin secretion and its components in the first-degree relatives of type 2 diabetics / 中华内分泌代谢杂志

Objective To investigate the changes of first-phase insulin secretion and its components in the first-degree relatives of Chinese type 2 diabetics with normal glucose tolerance and their correlation with type 2 diabetes. Methods The first-degree relatives of type 2 diabetes (Group B, n=35), newly diagnosed type 2 diabetic patients (Group C, n=35) and health subjects (Group A, n=21) were recruited. Immune reactive insulin (IRI), proinsulin (PI), and true insulin (TI) were determined during intravenous glucose tolerance test (IVGTT) in each subjects. IRI was determined with radioimmunoassay kit, while PI and TI with ELISA kits. Results (1) For the fasting sera, the levels of IRI and PI showed significant differences (both P