Japanese 17q12 Deletion Syndrome with Complex Clinical Manifestations.

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.

Weight Gain After 20 Years of Age is Associated with Unfavorable Lifestyle and Increased Prevalence of Metabolic Disorders.

PURPOSE: It is unclear what kind of modifiable lifestyle factors are associated with long-time weight gain in adulthood. To clarify the lifestyle behavior related to body weight gain since the age of 20 years, we explored the lifestyle risk factor, independently associated with excessive weight gain after 20 years of age as compared to those in subjects with a stable weight, with matching of age, gender, and the current body mass index (BMI). PATIENTS AND METHODS: From baseline data of a general population-based cohort study, we designed a cross-sectional analysis collecting individual data of medical health check-ups and a questionnaire related to lifestyle, including amount of sleep, frequency of eating breakfast, average times per day engaged in walking and sitting in the prior year, and smoking habits. These data were compared between the subjects with weight gain ≥10kg (n=3601) and <10kg (n=3601) after age 20, matched by a propensity score model which included current BMI, age and gender. We used multivariable logistic regressions to assess the lifestyle factor's association with high weight gain. RESULTS: Participants who gained ≥10 kg were significantly more likely to sleep <5 hours or ≥9 hours per night, skip breakfast, engage in walking <1 hour per day, and sit ≥5 hours per day than those who gained <10kg. Multivariable logistic regressions analyses showed that, with adjusting for potential confounder, the lifestyles with the positive association with high weight gain were skipping breakfast (OR 1.252; 95% CI 1.053-1.489, vs regularly), long sleeping duration (9 hours/day≤ OR 1.613; 95% CI 1.018-2.557 vs 5≤-<7 hours/day), and former smoker (OR 1.163; 95% CI 1.008-1.343 vs never smoker), while walking duration was negatively associated with high weight gain. Furthermore, despite similar current BMI, participants with weight gain ≥10kg had significantly higher values for waist circumference, blood pressure, HbA1c, LDL-C, triglycerides, and hepatic enzyme levels than those with weight gain <10kg. Similarly, the prevalence rates of hypertension, dyslipidemia, metabolic syndrome (MetS), and former smoker were higher in the participants with weight gain ≥10kg. CONCLUSION: Major weight gain after 20 years of age was associated with unfavorable lifestyle factors and greater waist circumference, possibly leading to elevated risk for MetS and other non-communicable diseases. These findings highlight the importance of maintaining both weight at age 20 and a favorable lifestyle throughout adulthood.

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.