Relationships between computed tomography-assessed density, abdominal fat volume, and glucose metabolism after sleeve gastrectomy in Japanese patients with obesity.

In this study, we investigated the relationships between body weight (BW), computed tomography (CT)-assessed abdominal adipose tissue, and the glycemic metabolic profile in obese Japanese patients following laparoscopic sleeve gastrectomy (LSG). This study analyzed adipose tissue compartments using CT methods before and 1 year after LSG. Thirty obese patients were studied, and variables measured included visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), density of VAT (VAT-D), and density of SAT (SAT-D). We also examined the parameters in patients according to whether they had type-2 diabetes (T2DM). LSG induced significant losses in BW, SAT, and VAT after LSG. Additionally, SAT-D and VAT-D both increased and fasting plasma glucose (FPG) and HbA1c, but not C-peptide, decreased after surgery. ΔSAT and ΔVAT were positively related, and ΔSAT-D and ΔVAT-D were negatively related to ΔBW and/or FPG. Furthermore, a multivariate regression model showed that total BW loss (TBWL) was closely related to ΔSAT (ß = 0.84; p < 0.001) and ΔVAT-D (ß = -0.45; p < 0.05) and improvement of FPG was related to ΔVAT (ß = 0.61; p < 0.05) after LSG. Finally, ΔFPG was correlated with ΔVAT in 16 T2DM patients (r = 0.58; p < 0.05) but not in non-T2DM patients. TBWL was related to ΔSAT and ΔVAT-D, and improvement of FPG was related to ΔVAT in obese Japanese patients after LSG.

Bioelectrical Impedance Analysis Results for Estimating Body Composition Are Associated with Glucose Metabolism Following Laparoscopic Sleeve Gastrectomy in Obese Japanese Patients.

We investigated the association between body composition and changes in glucose metabolism following laparoscopic sleeve gastrectomy (LSG) in obese Japanese patients. Thirty-two Class III obese patients were assessed before LSG and 3, 6, and 12 months postoperatively. Variables including fat mass (FM), % body fat (%FM), total and skeletal muscle mass (MM), the ratio of lower extremity MM to body weight (BW) (L/W), and the ratio of upper extremity MM to BW (U/W) were measured while using bioelectrical impedance analysis (BIA). LSG significantly decreased BW, FM, and %FM in all time periods observed after surgery with concomitant improvements in metabolic markers. MM was decreased at three months but maintained from 3⁻12 months post-surgery. Importantly, %MM, U/W, and the L/W ratio increased after LSG. Furthermore, change in FM was positively correlated with change in BW 12 months after LSG, whereas changes in %MM were negatively correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Finally, multivariable stepwise regression analyses showed that changes in % total MM was an independent determinant of FPG and change in % skeletal MM was a significant independent determinant of HbA1c in Class III obese Japanese patients after LSG.

Glucagon-like peptide-1 reduces pancreatic ß-cell mass through hypothalamic neural pathways in high-fat diet-induced obese rats.

We examined whether glucagon-like peptide-1 (GLP-1) affects ß-cell mass and proliferation through neural pathways, from hepatic afferent nerves to pancreatic efferent nerves via the central nervous system, in high-fat diet (HFD)-induced obese rats. The effects of chronic administration of GLP-1 (7-36) and liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, c-fos expression and brain-derived neurotrophic factor (BDNF) content in the hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese rats elevated c-fos expression and BDNF content in the hypothalamus, followed by a reduction in pancreatic ß-cell hyperplasia and insulin content, thus resulting in improved glucose tolerance. These responses were abolished by VgX and SpX. Moreover, administration of liraglutide similarly activated the hypothalamic neural pathways, thus resulting in a more profound amelioration of glucose tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the obesity-induced compensatory increase in ß-cell mass and glucose intolerance through a neuronal relay system consisting of hepatic afferent nerves, the hypothalamus, and pancreatic efferent nerves.

Role of spleen-derived IL-10 in prevention of systemic low-grade inflammation by obesity [Review].

Obesity can be associated with systemic low-grade inflammation that leads to obesity-related metabolic disorders. Recent studies raise the possibility that the inflammation in hypothalamus, liver and white adipose tissue (WAT) contributes to the pathogenesis of diet-induced obesity. We focus on the role of interleukin (IL)-10, an anti-inflammatory cytokine produced from spleen in obesity because it is indicated that obesity decreases the expression of pro-inflammatory cytokines in spleen. Obesity results in decrease of IL-10 synthesis from spleen, probably due to reduction of B-cells expression by promoting oxidative stress and apoptosis in spleen. Splenectomy (SPX) aggravates the inflammatory response in hypothalamus, liver and WAT. These SPX-induced alterations are inhibited by systemic administration of IL-10. Moreover, in IL-10 deficiency, SPX had little effect on the inflammatory responses in these multiple organs. We show the role of spleen-derived IL-10 on inflammatory responses in obesity.

Fulminant type 1 diabetes mellitus with anti-programmed cell death-1 therapy.

Anti-programmed cell death-1 (PD-1) antibodies are regarded as a risk factor for insulin-dependent diabetes mellitus as a side-effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin-dependent diabetes during anti-PD-1 therapy. A 55-year-old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C-peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti-PD-1 therapy can cause rapid onset of insulin-dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti-PD-1 therapy.

Effects of hydrophilic statins on renal tubular lipid accumulation in diet-induced obese mice.

Animal models of obesity show that lipid deposits can injure the kidneys,and there is evidence for the role of lipids in the development of chronic renal dis-ease (CKD). Statins exhibit a lipid-lowering effect that acts on both total cholesterol and triglyceride (TG) levels and pleiotropic effects including their ability to reduce inflammation and fibrosis. The purpose of the present study was to confirm whether obesity induced by a high-fat diet (HFD, 60% fat) promotes lipid accumulation in the tubulointerstitial and/or glomerular areas in the kidney, and whether treatment of several statins, pravastatin (30 mg/kg, p.o.), rosuvastatin (3 mg/kg, p.o.),pitavastatin (1 mg/kg, p.o.) and atorvastatin (10 mg/kg, p.o.), suppresses obesity-induced lipid accumulation. Using male C57Bl/6J mice, we examined parameters related to energy metabolism, lipid accumulation as well as macrophage infiltration in glomeruli and the tubulointerstitial area, and glomerular injury using nephrin and desmin expression. None of the statins affected body weight, glucose metabolism,serum TG and adiponectin levels, or serum inflammatory cytokine levels. However,all statins improved lipid accumulation in the proximal tubules, improved glomerular hypertrophy, increased nephrin expression and decreased desmin expression, compared to non-treated obese animals. Moreover, the reduction of proximal tubular lipid accumulation was greater with pravastatin and rosuvastatin treatment than with pitavastatin and atorvastatin treatment. We concluded that hydrophilic statins may be more effective for preventing lipid accumulation in renal tubules than lipophilic statins.

Hyperhomocysteinemia is associated with visceral adiposity in Japanese patients with type 2 diabetes mellitus.

This study aims to investigate the relationship between the circulating level of homocysteine and body adiposity in Japanese patients with type 2 diabetes mellitus. We measured the body mass index (BMI), waist and hip circumferences, visceral and subcutaneous adiposities, visceral/subcutaneous (V/S) adiposity ratio, and insulin resistance as assessed by the Homeostasis Model Assessment (HOMA) index in patients with hyperhomocysteinemia. The study group consisted of 17 Japanese patients with type 2 diabetes and hyperhomocysteinemia (age: 62+/-10 years, mean+/-S.D.), and the control group consisted of 24 age-matched type 2 diabetes patients with normohomocysteinemia (60+/-11 years). The visceral adiposity, HOMA index, and V/S ratio were significantly higher in the hyperhomocysteinemia group than in the normohomocysteinemia group (P<0.05). In contrast, the BMI, hip circumference, and subcutaneous adiposity were similar between the two groups (P>0.1). Furthermore, multiple regression analysis showed that hyperhomocysteinemia was closely related to insulin resistance and visceral adiposity. Our results indicate that the presence of hyperhomocysteinemia in our population of Japanese patients with type 2 diabetes-associated insulin resistance was associated with increased visceral but not subcutaneous adiposity.