Hajime Ishiguro

Meta‐analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus

Our aim is to examine the dose–response association between cumulative genetic risk and actual risk of type 2 diabetes mellitus (T2DM) and the influence of adjustment for covariates on T2DM risk through a comprehensive meta‐analysis of observational studies.

Relationships among cardiorespiratory fitness, muscular fitness, and cardiometabolic risk factors in Japanese adolescents: Niigata screening for and preventing the development of non-communicable disease study-Agano (NICE EVIDENCE Study-Agano) 2

To examine the independent and combined associations of cardiorespiratory fitness (CRF) and muscular fitness (MF) with cardiometabolic risk factors in Japanese adolescents.

Unstable bodyweight and incident type 2 diabetes mellitus: A meta-analysis

The present meta‐analysis aimed to clarify the association of unstable bodyweight with the risk of type 2 diabetes mellitus, an association that has been controversial among longitudinal studies.

A case of hypoglycemia attributable to atypical antipsychotic drugs

AbstractWe report a 55-year-old Japanese man who presented with symptomatic hypoglycemia attributable to atypical antipsychotic drugs (APD). He had been taking olanzapine, quetiapine, and paliperidone. One morning, his consciousness level dropped without inducement and his blood glucose was low. His symptoms improved after intravenous glucose infusion. These episodes reoccurred a few times, but ceased after APD were stopped. Physical examination did not find any organic disease that might cause hypoglycemia. Hyperglycemia, dyslipidemia, and body weight gain are well-documented side-effects of APD, but hypoglycemia is rare. There are a variety of hypotheses on how APD cause hypoglycemia: (1) Weight gain and dyslipidemia caused by APD might increase insulin resistance, meaning that excess insulin is secreted, causing hypoglycemia. (2) The quantity of basal insulin secreted by pancreatic beta cells might be enhanced by APD, which might cause hypoglycemia. (3) APD might work as an antagonist of muscarinic receptors such that insulin secretion might continue even after the glucose level has returned to normal, which might cause hypoglycemia. However, the mechanism is not fully understood and more research is needed.

Network meta-analysis of the relative efficacy of bariatric surgeries for diabetes remission: Network meta-analysis of bariatric surgeries

Bariatric surgery leads to a higher remission rate for type 2 diabetes mellitus than non‐surgical treatment. However, it remains unsolved which surgical procedure is the most efficacious. This network meta‐analysis aimed to rank surgical procedures in terms of diabetes remission.

Quantitative Relationship Between Cumulative Risk Alleles Based on Genome-Wide Association Studies and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Many epidemiological studies have assessed the genetic risk of having undiagnosed or of developing type 2 diabetes mellitus (T2DM) using several single nucleotide polymorphisms (SNPs) based on findings of genome-wide association studies (GWAS). However, the quantitative association of cumulative risk alleles (RAs) of such SNPs with T2DM risk has been unclear. The aim of this meta-analysis is to review the strength of the association between cumulative RAs and T2DM risk. Systematic literature searches were conducted for cross-sectional or longitudinal studies that examined odds ratios (ORs) for T2DM in relation to genetic profiles. Logarithm of the estimated OR (log OR) of T2DM for 1 increment in RAs carried (1-ΔRA) in each study was pooled using a random-effects model. There were 46 eligible studies that included 74,880 cases among 249,365 participants. In 32 studies with a cross-sectional design, the pooled OR for T2DM morbidity for 1-ΔRA was 1.16 (95% confidence interval [CI], 1.13–1.19). In 15 studies that had a longitudinal design, the OR for incident T2DM was 1.10 (95% CI, 1.08–1.13). There was large heterogeneity in the magnitude of log OR (P < 0.001 for both cross-sectional studies and longitudinal studies). The top 10 commonly used genes significantly explained the variance in the log OR (P = 0.04 for cross-sectional studies; P = 0.006 for longitudinal studies). The current meta-analysis indicated that carrying 1-ΔRA in T2DM-associated SNPs was associated with a modest risk of prevalent or incident T2DM, although the heterogeneity in the used genes among studies requires us to interpret the results with caution.

Genetically Reduced Chondroitin Sulfate Prevents the Progression of Diabetic Neuropathy

Background: The extracellular matrix is associated with the pathophysiology of diabetic complications; however, the role of chondroitin sulfate (CS) remains unclear. To clarify the effects of CS on diabetic neuropathy (DN), we assessed the effect of genetically reducing CS in mice through disruption of a gene encoding the rate-limiting CS-synthesizing enzyme, i.e., CS N-acetylgalactosaminyltransferase-1 (T1). Methods: T1 knockout (T1KO) mice were generated from the C57BL/6N strain and C57BL/6N were prepared as wild type (WT). Diabetes was induced through streptozotocin injection in 6-week-old male mice. All data were obtained 3 weeks after streptozotocin injection. Results: In the heat radiant test, while thermal nociception in nondiabetic WT and T1KO mice were normal and significantly disrupted in diabetic WT mice, that in diabetic T1KO mice was preserved. The number of plantar peripheral nerve fibers was also significantly decreased in diabetic WT mice; however, that in diabetic T1KO mice were relatively normal. Furthermore, immunohistochemistry revealed loss of calcitonin gene-related peptide-positive neurons in the dorsal root ganglia (DRG) in diabetic WT mice, which contains a cluster of sensory neuron bodies. In contrast, those neurons were protected in diabetic T1KO mice. Hence, nociception and thermoception are preserved in diabetic T1KO mice. To investigate the mechanisms underlying these events, we analyzed gene expression in DRG through real-time polymerase chain reaction and confirmed the suppression of caspase-3 and caspase-9 in diabetic T1KO mice, compared to those in diabetic WT mice. However, levels of Bcl2, TNF-α, MMP9, and reactive oxygen species-related enzymes (HO-1, NOX) did not differ significantly between WT and T1KO diabetic mice. Conclusions: Reduced CS production is suggested to have potentially beneficial effects on preventing DN by suppressing apoptotic signaling and could be a cutting-edge target of clinical application. Disclosure H. Ishiguro: Research Support; Self; MSD K.K., Sanofi K.K., Eli Lilly and Company. T. Ushiki: None. A. Kawasaki: None. K. Cho: None. M. Masuko: None. K. Sango: None. M. Igarashi: None. H. Sone: Research Support; Self; Novo Nordisk Inc., Eli Lilly and Company, MSD K.K., Chugai Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Daiichi Sankyo Company, Limited, Ono Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Sanofi, Kowa Pharmaceuticals America, Inc., Eisai Inc..

A case of normotensive incidentally discovered adrenal pheochromocytoma

Pheochromocytomas are catecholamine‐producing neuroendocrine tumors that arise from the adrenal medulla. The clinical presentation includes headache, palpitation, and hypertension, but pheochromocytomas are sometimes clinically silent. The present case highlights the importance of biochemical testing for pheochromocytoma in patients with adrenal incidentaloma, even if they are completely normotensive and asymptomatic.

Role of fatty liver in the association between obesity and reduced hepatic insulin clearance

AIM Hepatic insulin clearance (HIC) is important in regulating plasma insulin levels. Diminished HIC causes inappropriate hyperinsulinaemia, and both obesity and fatty liver (FL), which are known to decrease HIC, can be found either together in the same patient or on their own. The mechanism by which obesity reduces HIC is presumed to be mediated by FL. However, few reports have examined the role of FL in the relationship between obesity and HIC in type 2 diabetes (T2D) patients. Therefore, our study investigated the association of HIC with clinical factors, including insulin sensitivity indices, focusing on the presence or absence of FL and obesity in T2D patients. METHOD Baseline data from 419 patients with T2D (279 men, 140 women; mean age: 57.6 years; body mass index: 25.5kg/m2) controlled by diet and exercise were analyzed. HIC was calculated from the ratio of fasting c-peptide to fasting insulin levels (HICCIR). Correlation analyses between HICCIR and clinical variables were performed using Pearsons product-moment correlation coefficients and single regression analysis in all participants and in those with obesity and FL either alone or in combination. RESULTS HICCIR was significantly correlated with whole-body insulin sensitivity indices and influenced by FL, but only in the FL group was obesity independently influenced HIC level. HICCIR decreased in those with both FL and obesity compared with those with only one such complication. CONCLUSION HICCIR may be used to evaluate whole-body insulin sensitivity in T2D. Also, compared with obesity, the influence of FL strongly contributed to a reduced HIC. TRIAL REGISTRATION NUMBER These trials were registered by the Japan Pharmaceutical Information Centre clinical trials information (JapicCTI) as 101349 and 101351.

Utility of nonblood-based risk assessment for predicting type 2 diabetes mellitus: A meta-analysis

OBJECTIVE Nonblood-based risk assessment for type 2 diabetes mellitus (T2DM) that depends on data based on a questionnaire and anthropometry is expected to avoid unnecessary diagnostic testing and overdiagnosis due to blood testing. This meta-analysis aims to assess the predictive ability of nonblood-based risk assessment for future incident T2DM. METHODS Electronic literature search was conducted using EMBASE and MEDLINE (from January 1, 1997 to October 1, 2014). Included studies had to use at least 3 predictors for T2DM risk assessment and allow reproduction of 2×2 contingency table data (i.e., true positive, true negative, false positive, false negative) to be pooled with a bivariate random-effects model and hierarchical summary receiver-operating characteristic model. Considering the importance of excluding individuals with a low likelihood of T2DM from diagnostic blood testing, we especially focused on specificity and LR-. RESULTS Eighteen eligible studies consisting of 184,011 participants and 7038 cases were identified. The pooled estimates (95% confidence interval) were as follows: sensitivity=0.73 (0.66-0.79), specificity=0.66 (0.59-0.73), LR+=2.13 (1.81-2.50), and LR-=0.41 (0.34-0.50). CONCLUSIONS Nonblood-based assessment of risk of T2DM could produce acceptable results although the feasibility of such a screener needs to be determined in future studies.