Visceral Fat Accumulation Is Associated with Asthma in Patients with Type 2 Diabetes.

OBJECTIVE: The number of patients with type 2 diabetes has increased in Japan, and type 2 diabetes has attracted attention as a risk factor for asthma. However, the risk factors for the development of asthma in patients with type 2 diabetes have not been determined. This study was performed to clarify whether visceral fat accumulation (VFA) and insulin resistance are risk factors for the development of asthma in patients with type 2 diabetes. MATERIALS AND METHODS: A cross-sectional study was conducted. The study group comprised 15 patients with type 2 diabetes with asthma, and the control group comprised 145 patients with type 2 diabetes without asthma. Their fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. Their glucose status was assessed by measuring the fasting plasma glucose (FPG) concentration, fasting immunoreactive insulin concentration, homeostasis model assessment (HOMA) index, and hemoglobin A1c concentration. RESULTS: Among patients with type 2 diabetes, VFA was significantly greater in patients with asthma than those without asthma (P < 0.0001). The FPG concentration, fasting immunoreactive insulin concentration, and HOMA index were higher in patients with asthma than those without asthma (P < 0.05, P < 0.0001, and P < 0.0001, respectively). Multiple logistic regression analysis showed that VFA and the HOMA index were significantly associated with asthma in patients with type 2 diabetes (odds ratio, 1.78; 95% confidence interval, 1.31-3.89; P = 0.0115 and odds ratio, 3.65; 95% confidence interval, 1.37-7.85; P = 0.0078, respectively). CONCLUSIONS: Our data suggest that VFA and insulin resistance are associated with the development of asthma in patients with type 2 diabetes.

TYK2 Promoter Variant and Diabetes Mellitus in the Japanese.

BACKGROUND: Recently, 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). METHODS: Polymorphisms 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. FINDINGS: A 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. INTERPRETATION: The TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans. FUNDING: Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan.

Homocysteine levels are associated with hippocampus volume in type 2 diabetic patients.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are associated with cognitive dysfunction, in which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that elevated tHcy levels are correlated with hippocampus volume and insulin resistance in nondementia patients with type 2 diabetes. MATERIALS AND METHODS: The study included 43 nondementia patients with type 2 diabetes, who were divided into two groups: a high tHcy group (age: 65 ± 8 years, mean ± standard deviation, n = 16) and a normal tHcy group (64 ± 9 years, n = 27). Hippocampus volume was quantified with a computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer's disease (VSRAD), which yields a Z-score as the end point for the assessment of hippocampal volume. Results The Z-score was higher in the high tHcy group compared to the normal tHcy group (P < 0·0001). The fasting plasma glucose (P < 0·01) and insulin (P < 0·0001) concentrations and the homoeostasis model assessment (HOMA) index (P < 0·0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis showed that the main factors that influenced tHcy levels may be the Z-score and the HOMA index. CONCLUSIONS: Our results indicate that the elevated levels of tHcy in Japanese nondementia patients with type 2 diabetes are characterised by hippocampal atrophy and insulin resistance and that the Z-score and HOMA index may be the primary factors that influence tHcy levels.

High-sensitivity C-reactive protein is associated with hippocampus volume in nondementia patients with type 2 diabetes mellitus.

The elevated level of high-sensitivity C-reactive protein (HSCRP) is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of HSCRP correlates with hippocampus volume and insulin resistance in nondementia patients with type 2 diabetes mellitus. Subjects included 45 nondementia patients with type 2 diabetes mellitus, who were divided into 2 groups: high-HSCRP group (age, 65 ± 6 years [mean ± SD]; n = 17) and normal-HSCRP group (65 ± 7 years, n = 28). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging voxel-based specific regional analysis system developed for the study of Alzheimer disease (VSRAD), which yields a z score as the end point for assessment of hippocampal volume. The z score was higher in the high-HSCRP group than in the normal-HSCRP group (P < .0001). The fasting plasma glucose (P < .05) and insulin concentrations (P < .0001) and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-HSCRP group than in the normal-HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by z score and HOMA index. Our results indicate that the elevated level of HSCRP in Japanese nondementia patients with type 2 diabetes mellitus is characterized by increased hippocampus volume and insulin resistance, and that the z score and HOMA index are independent predictors of HSCRP.

Association between plasma high-sensitivity C-reactive protein and insulin resistance and white matter lesions in Japanese type 2 diabetic patients.

The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. High-sensitivity C-reactive protein (HSCRP), which is associated with diabetes, has been flagged as a novel predictor for cerebrovascular events. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with HSCRP and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Based on brain magnetic resonance imaging (MRI) findings, 102 type 2 diabetic patients were divided into two groups; a WML-positive group (59+/-6 years, mean+/-SD, n=40) and a WML-negative group (58+/-6 years, n=62). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, and Hemoglobin A1c (HbA1c). The body mass index was higher in the WML-positive group than in the WML-negative group (p<0.05). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol (HDL-C) was lower in the WML-positive group than in the WML-negative group (p<0.01 and p<0.005, respectively). Fasting plasma glucose (p<0.005), insulin concentrations (p<0.0001), HOMA index (p<0.0001), and HSCRP (<0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high HSCRP and insulin resistance (p<0.005, p<0.0005, respectively). The results of this preliminary study indicate that the presence of WML was associated with the high HSCRP and insulin resistance in these Japanese patients with type 2 diabetes mellitus; larger cohort studies are warranted to confirm these findings.

Diabetic retinopathy is associated with visceral fat accumulation in Japanese type 2 diabetes mellitus patients.

The presence of diabetic retinopathy (DR) and increased of visceral fat accumulation (VFA) are associated with high mortality in type 2 diabetes mellitus patients. This preliminary study was therefore designed to test the hypothesis that DR is associated with insulin resistance and VFA in type 2 diabetes mellitus patients without insulin treatment. A total of 102 type 2 diabetes mellitus patients were divided into 2 groups: DR group (age, 60 +/- 6 years [mean +/- SD]; n = 31) and no diabetic retinopathy (NDR) group (59 +/- 5 years, n = 71). The level of blood glucose was assessed by fasting plasma glucose, fasting immunoreactive insulin, homeostasis model assessment index, and hemoglobin A(1c). The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The body mass index and waist circumference were higher in the DR group than in the NDR group (P < .001 and P < .0005, respectively). Plasma levels of triglyceride were higher, whereas high-density lipoprotein cholesterol was lower, in the DR group than in the NDR group (P < .005 and P < .0001, respectively). Fasting plasma glucose (P < .0005), insulin concentrations (P < .0001), homeostasis model assessment index (P < .0001), and VFA (P < .0001) levels were higher in the DR group than in the NDR group. Multivariate logistic analysis revealed that DR was independently predicted by high VFA and insulin resistance. The results of this preliminary study indicate that the presence of DR was associated with high VFA and insulin resistance in Japanese patients with type 2 diabetes mellitus.

Abdominal visceral fat accumulation is associated with hippocampus volume in non-dementia patients with type 2 diabetes mellitus.

Obesity is associated with cognitive dysfunction, for which changes in the hippocampus plausibly play a pivotal role. We tested the hypothesis that an elevated level of visceral fat accumulation (VFA) correlates with hippocampus volume and insulin resistance in non-dementia patients with type 2 diabetes. Subjects included 48 non-dementia patients with type 2 diabetes, who were divided into two groups, high VFA group (mean+/-standard deviation: age=65+/-6 years, n=30) and normal VFA group (65+/-5 years, n=18). Hippocampus volume has been quantitated with computer-assisted analysis using a magnetic resonance imaging (MRI) voxel-based specific regional analysis system developed for the study of Alzheimer's disease (VSRAD), which yields a Z-score as the end point for assessment of hippocampal volume. The Z-score was higher in the high VFA group than in the normal VFA group (p<0.0001). The fasting plasma glucose (p<0.05) and insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index (p<0.0001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that VFA levels were independently predicted by Z-score and HOMA index. Our results indicate that the elevated level of VFA in Japanese non-dementia patients with type 2 diabetes is characterized by increased hippocampus volume and insulin resistance, and that the Z-score and HOMA index are independent predictors of VFA.

The role of microalbuminuria and insulin resistance as significant risk factors for white matter lesions in Japanese type 2 diabetic patients.

OBJECTIVE: The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Microalbuminuria, which is associated with diabetes, has been flagged as a novel predictor for cerebrovascular events. This preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with microalbuminuria and insulin resistance in patients with type 2 diabetic mellitus (DM) not receiving insulin treatment. PATIENTS AND METHODS: Based on brain magnetic resonance imaging (MRI) findings, 90 type 2 diabetic patients were divided into two groups: a WML-positive group (57+/-8 years, mean+/-SD, n=34) and a WML-negative group (57+/-6 years, n=56). The level of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, and hemoglobin A(1c) (HbA1c). RESULTS: The body mass index was higher in the WML-positive group than in the WML-negative group (p<0.01). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol (HDL-C) was lower in the WML-positive group than in the WML-negative group (p<0.05 and p<0.0001, respectively). Fasting plasma glucose (p<0.005), insulin concentrations (p<0.0001), HOMA index (p<0.0001), and urinary albumin excretion (p<0.0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the microalbuminuria and insulin resistance (p<0.005, p<0.0005, respectively). CONCLUSION: The results of this preliminary study indicate that the presence of WML was associated with the microalbuminuria and insulin resistance in these Japanese patients with type 2 DM; larger cohort studies are warranted to confirm these findings.

Correlations of visceral fat accumulation and atherosclerosis in Japanese patients with type 2 diabetes mellitus.

We tested the hypothesis that increased abdominal visceral fat accumulation (VFA) is associated with insulin resistance and aortic stiffness in patients with type 2 diabetes mellitus not receiving insulin treatment. The study consisted of 22 Japanese patients with type 2 diabetes mellitus and high VFA (> or =100 cm(2); age, 61 +/- 7 years; high VFA group) and a control group of 18 age-matched patients with normal VFA (<100 cm(2); age, 60 +/- 8 years; normal VFA group). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. The BaPWV was used as an index of atherosclerosis. The body mass index values (P < .05), waist circumferences (P < .0005), and waist-to-hip ratios (P < .05) were larger in the high VFA group than in the normal VFA group. The BaPWV was higher in the high VFA group than in the normal VFA group (P < .0001). Fasting plasma glucose (P < .05), insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that the VFA level was independently predicted by BaPWV and the HOMA index. Our results indicate that the elevation of VFA in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance and that BaPWV and the HOMA index are independent predictors of VFA.

Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients.

Elevated total plasma homocysteine (tHcy) level and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that tHcy correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 40 Japanese patients with type 2 diabetes mellitus and high tHcy levels (mean age +/- SD, 57 +/- 7 years) and a control group of 45 age-matched patients with normal tHcy levels (mean age +/- SD, 57 +/- 6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by an automatic oscillometric method. Brachial-ankle pulse wave velocity was used as an index of atherosclerosis. Body mass index values (P < .05), waist circumferences (P < .05), and the waist-to-hip ratios (P < .05) were larger in the high-tHcy group than in the normal-tHcy group. The BaPWV was higher in the high-tHcy group than in the normal-tHcy group (P < .0001). Fasting plasma glucose (P < .005) and insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-tHcy group than in the normal-tHcy group. Multiple regression analysis showed that tHcy levels were independently predicted by BaPWV and the HOMA index. In conclusion, our results indicate that the elevated level of tHcy in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and the HOMA index are independent predictors of tHcy.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients.

BACKGROUND: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. MATERIAL AND METHODS: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. RESULTS: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. CONCLUSIONS: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients.

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.

Churg-strauss syndrome with cholecystitis and renal involvement.

A patient with bronchial asthma developed cholecystitis. Laboratory investigations revealed marked eosinophilia (6,615/mm3), an elevated anti-neutrophil cytoplasmic antibody level and renal dysfunction (blood urea nitrogen 14 mg/dl, creatinine 1.4 mg/dl). Following cholecystectomy, histopathological examination revealed a marked inflammatory cell infiltrate composed mainly of eosinophils with evidence of invasion of the wall of the gall bladder and granuloma formation of arterioles. A diagnosis of Churg-Strauss syndrome was made and she was treated with 60 mg of prednisolone per day. A renal biopsy was performed one year later in view of persistent renal dysfunction. Pathological analysis revealed a pauci-immune glomerulonephritis with interstitial changes but no crescent formation.

[A case of primary Sjögren's syndrome with severe pulmonary hypertension and glomerular damage].

We report a case of 58 years old female with primary Sjögren's syndrome who accompanied pulmonary hypertension and glomerular damage. Renal biopsy revealed interstitial nephritis and glomerular damage. Pulmonary perfusion scintigram revealed diffusely decreased pulmonary perfusion, but the defect was not observed. Immunocomplex positive indicated that immune disorder would damage her lung and kidney. Proteinuria and pulmonary hypertension were improved by high dose of prednisolone and low dose of oral cyclophosphamide treatment. No previous reports had shown pulmonary hypertension and glomerular damage complicated with primary Sjögren's syndrome in same patients at same time. But some reports had suggested immune disorder had caused pulmonary hypertension or glomerulonephritis in patients of primary Sjögren's syndrome. Our patient showed immune disorder, and it might cause pulmonary hypertension and glomerular damage.