Association of epicardial adipose tissue with serum level of cystatin C in type 2 diabetes.

OBJECTIVE: Accumulation of epicardial adipose tissue (EAT) is considered to be a cardiovascular risk factor independent from visceral adiposity, obesity, hypertension and diabetes. We explored the parameters related to EAT accumulation, aiming to clarify the novel pathophysiological roles of EAT in subjects with type 2 diabetes (T2DM). METHODS: We examined the laboratory values, including cystatinC, and surrogate markers used for evaluating atherosclerosis. EAT was measured as the sum of the adipose tissue area, obtained by plain computed tomography scans in 208 subjects with T2DM but no history of coronary artery disease. RESULTS: EAT correlated positively with age, body mass index (BMI), visceral fat area, leptin, cystatin C and C-peptide, while correlating negatively with adiponectin, estimated glomerular filteration rate (eGFR) and the liver-to-spleen ratio. Multiple linear regression analysis revealed serum cystatin C (ß = 0.175), leptin (ß = 0.536), BMI (ß = 0.393) and age (ß = 0.269) to be the only parameters showing independent statistically significant associations with EAT. When cystatin C was replaced with eGFR, eGFR showed no significant correlation with EAT. In reverse analysis, serum cystatin C was significantly associated with EAT after adjustment in multivariate analysis. DISCUSSION: EAT accumulation and elevated cystatin C have been independently regarded as risk factors influencing atherosclerosis. The strong association between EAT and cystatin C demonstrated herein indicates that EAT accumulation may play an important role in Cystatin C secretion, possibly contributing to cardiometabolic risk in T2DM patients.

Association of Advanced Glycation End Products with coronary Artery Calcification in Japanese Subjects with Type 2 Diabetes as Assessed by Skin Autofluorescence.

AIM: Advanced glycation end products (AGE) are considered to be among the critical pathogenic factors involved in the progression of diabetic complications. Skin autofluorescence (AF), a noninvasive measurement of AGE accumulation, has been recognized as a useful and convenient marker for diabetic vascular diseases in Caucasians. This study aimed to evaluate the association of tissue AGE, assessed using skin AF, with coronary artery calcification in Japanese subjects with type 2 diabetes. METHODS: In total, 122 Japanese subjects with type 2 diabetes enrolled in this cross-sectional study underwent multi-slice computed tomography for total coronary artery calcium scores (CACS) estimation and examination with a skin AF reader. RESULTS: Skin AF positively correlated with age, sex, diabetes duration, pulse wave velocity, systolic blood pressure, serum creatinine, and CACS. In addition, skin AF results negatively correlated with BMI, eGFR, and serum C-peptide concentration. According to multivariate analysis, age and systolic blood pressure showed strong positive correlation and eGFR showed negative correlation with skin AF values. Multiple linear regression analyses revealed a significant positive correlation between skin AF values and logCACS, independent of age, sex, diabetes duration, HbA1c, BMI, IMT, and blood pressure. However, skin AF showed no association with serum levels of AGE, such as Nε-(carboxymethyl) lysine and 3-deoxyglucosone. CONCLUSION: Skin AF results positively correlated with CACS in Japanese subjects with type 2 diabetes. This result indicates that AGE plays a role in the pathogenesis of diabetic macrovascular disease. Measurement of skin AF values may be useful for assessing the severity of diabetic complications in Japanese subjects.

Response to the dipeptidyl peptidase-4 inhibitors in Japanese patients with type 2 diabetes might be associated with a diplotype of two single nucleotide polymorphisms on the interleukin-6 promoter region under a certain level of physical activity.

AIMS/INTRODUCTION: Muscle-derived interleukin-6 (IL-6) has been reported to promote glucagon-like peptide-1 (GLP-1) secretion, and we explored the association of single nucleotide polymorphisms (SNPs) in the human IL-6 promoter region with the responsiveness to dipeptidyl peptidase-4 inhibitors (DPP-4Is), drugs that increase circulating GLP-1. MATERIALS AND METHODS: The present observational study enrolled Japanese patients with type 2 diabetes who took a DPP-4I over 3 months, and most of the clinical information was collected retrospectively. We defined non-responders as those having less than a 0.2% decrease of the glycated hemoglobin level at 3 or 4 months after starting DPP-4I treatment. Physical activity was retrospectively estimated by the Japanese short version of International Physical Activity Questionnaire. RESULTS: We studied 316 patients whose physical activity corresponding to the season of the DPP-4I administration was estimated. The non-responder rate was 29.7%. We analyzed rs1800796 and rs2097677, both are suggested to be functional in Japanese. Multivariate analysis for all patients showed that the adjusted odds ratio for the non-responder risk of the diplotype rs1800796 G/*-rs2097677 A/* against C/C-G/G (OR_G*A*) was 0.445 (P = 0.068). When patients were stratified by the International Physical Activity Questionnaire into low (n = 149) and moderate/high (n = 167) activity groups, however, OR_G*A* in each group was 1.58 (P = 0.615) and 0.153 (P = 0.003), respectively. CONCLUSIONS: The diplotype rs1800796 G/*-rs2097677 A/* might contribute to responsiveness to DPP-4Is in Japanese patients with type 2 diabetes under a certain level of physical activity. However, further investigation is warranted to confirm this.

Association of coronary artery calcification with MDA-LDL-C/LDL-C and urinary 8-isoprostane in Japanese patients with type 2 diabetes.

OBJECTIVE: Oxidative stress has been implicated in the development of coronary artery calcification (CAC). However, there are few reports on this issue in Japanese patients with diabetes. In this study, we examined the association of the CAC score (CACS) with oxidative stress markers. METHODS: The study subjects were 163 Japanese patients with type 2 diabetes (75 men and 88 women). The CACS (Agatston unit: AU) was measured by multi-detector computed tomography (MDCT), and the oxidative stress markers, such as the urinary 8-isoprostane and 8-hydroxydeoxyguanosine (8-OHdG) and serum malondialdehyde (MDA)-LDL cholesterol were measured. The relationships between CACS and oxidative stress markers were statistically analyzed. RESULTS: Compared with the CACS 0-400 AU group (n=132), the age, duration of diabetes, urinary 8-isoprostane levels, serum MDA-LDL-C/LDL-C and maximum intima media thickness (IMT) were higher, and body mass index and HbA1c level were lower, in the CACS >400 AU group (n=31). The multiple logistic regression analysis showed that a CAC >400 AU was independently associated with the urinary 8-isoprostane (>median) (OR=2.54, 95% CI=1.03-6.32, p=0.044), MDA-LDL-C/LDL-C (>median) (OR=2.62, 95% CI=1.07-6.40, p=0.035) and HbA1c (>median) (OR=0.32, CI=0.12-0.87, p<0.025). Focusing on oxidative stress, a higher MDA-LDL-C/LDL-C (p=0.026) and a higher urinary 8-isoprostane level (p=0.074) were associated with the CACS. CONCLUSION: The CACS was found to be independently associated with the MDA-LDL-C/LDL-C and urinary 8-isoprostane levels in Japanese patients with type 2 diabetes.