Kohei Kaku

Bio: Kohei Kaku is an academic researcher from Kawasaki Medical School. The author has contributed to research in topics: Diabetes mellitus & Type 2 diabetes. The author has an hindex of 44, co-authored 311 publications receiving 6921 citations. Previous affiliations of Kohei Kaku include Kawasaki University of Medical Welfare.

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

Abstract: We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).

Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy.

Abstract: To search for a gene(s) conferring susceptibility to diabetic nephropathy (DN), we genotyped over 80,000 genebased single nucleotide polymorphisms (SNPs) in Japanese patients and identified that the engulfment and cell motility 1 gene (ELMO1) was a likely candidate for conferring susceptibility to DN, in view of the significant association of an SNP in this gene with the disease (intron 189170, GG vs. GAAA, 2 19.9, P 0.000008; odds ratio 2.67, 95% CI 1.71‐4.16). In situ hybridization (ISH) using the kidney of normal and diabetic mice revealed that ELMO1 expression was weakly detectable mainly in tubular and glomerular epithelial cells in normal mouse kidney and was clearly elevated in the kidney of diabetic mice. Subsequent in vitro analysis revealed that ELMO1 expression was elevated in cells cultured under high glucose conditions (25 mmol/l) compared with cells cultured under normal glucose conditions (5.5 mmol/l). Furthermore, we identified that the expression of extracellular matrix protein genes, such as type 1 collagen and fibronectin, were increased in cells that overexpress ELMO1, whereas the expression of matrix metalloproteinases was decreased. These results indicate that ELMO1 is a novel candidate gene that both confers susceptibility to DN and plays an important role in the development and progression of this disease. Diabetes 54:1171‐1178, 2005

Association of the Gene Encoding Wingless-Type Mammary Tumor Virus Integration-Site Family Member 5B (WNT5B) with Type 2 Diabetes

Abstract: Recent reports have suggested that WNT signaling is an important regulator for adipogenesis or insulin secretion and might be involved in the pathogenesis of type 2 diabetes. To investigate possible roles of the WNT genes in conferring susceptibility to type 2 diabetes, we examined the association of the genes that encode members of the WNT family with type 2 diabetes in the Japanese population. First, 40 single-nucleotide polymorphism (SNP) loci within 11 WNT genes were analyzed in 188 subjects with type 2 diabetes (case-1) and 564 controls (control-1). Among them, six SNP loci exhibited a significant difference (P<.05) in the allele and/or genotype distributions between case and control subjects. These SNP loci were further analyzed in another set of case (case-2; n=733) and control (control-2; n=375) subjects to confirm their statistical significance. As a result, one SNP locus in the WNT5B gene was strongly associated with type 2 diabetes ( chi 2=15.6; P=.00008; odds ratio=1.74; 95% confidence interval 1.32-2.29). Expression of the WNT5B gene was detectable in several tissues, including adipose, pancreas, and liver. Subsequent in vitro experiments identified the fact that expression of the Wnt5b gene was increased at an early phase of adipocyte differentiation in mouse 3T3-L1 cells. Furthermore, overexpression of the Wnt5b gene in preadipocytes resulted in the promotion of adipogenesis and the enhancement of adipocytokine-gene expression. These results indicate that the WNT5B gene may contribute to conferring susceptibility to type 2 diabetes and may be involved in the pathogenesis of this disease through the regulation of adipocyte function.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes—2010

Abstract: D iabetes is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was used to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA multidisciplinary Professional Practice Committee, and new evidence is incorporated. Members of the Professional Practice Committee and their disclosed conflicts of interest are listed in the Introduction. Subsequently, as with all position statements, the standards of care are reviewed and approved by the Executive Committee of ADA’s Board of Directors.

Standards of Medical Care in Diabetes—2011

Abstract: I. CLASSIFICATION AND DIAGNOSIS OF DIABETES, p. S12 A. Classification of diabetes B. Diagnosis of diabetes C. Categories of increased risk for diabetes (prediabetes) II. TESTING FOR DIABETES IN ASYMPTOMATIC PATIENTS, p. S13 A. Testing for type 2 diabetes and risk of future diabetes in adults B. Testing for type 2 diabetes in children C. Screening for type 1 diabetes III. DETECTION AND DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS, p. S15 IV. PREVENTION/DELAY OF TYPE 2 DIABETES, p. S16 V. DIABETES CARE, p. S16 A. Initial evaluation B. Management C. Glycemic control 1. Assessment of glycemic control a. Glucose monitoring b. A1C 2. Glycemic goals in adults D. Pharmacologic and overall approaches to treatment 1. Therapy for type 1 diabetes 2. Therapy for type 2 diabetes E. Diabetes self-management education F. Medical nutrition therapy G. Physical activity H. Psychosocial assessment and care I. When treatment goals are not met J. Hypoglycemia K. Intercurrent illness L. Bariatric surgery M. Immunization VI. PREVENTION AND MANAGEMENT OF DIABETES COMPLICATIONS, p. S27 A. Cardiovascular disease 1. Hypertension/blood pressure control 2. Dyslipidemia/lipid management 3. Antiplatelet agents 4. Smoking cessation 5. Coronary heart disease screening and treatment B. Nephropathy screening and treatment C. Retinopathy screening and treatment D. Neuropathy screening and treatment E. Foot care VII. DIABETES CARE IN SPECIFIC POPULATIONS, p. S38 A. Children and adolescents 1. Type 1 diabetes Glycemic control a. Screening and management of chronic complications in children and adolescents with type 1 diabetes i. Nephropathy ii. Hypertension iii. Dyslipidemia iv. Retinopathy v. Celiac disease vi. Hypothyroidism b. Self-management c. School and day care d. Transition from pediatric to adult care 2. Type 2 diabetes 3. Monogenic diabetes syndromes B. Preconception care C. Older adults D. Cystic fibrosis–related diabetes VIII. DIABETES CARE IN SPECIFIC SETTINGS, p. S43 A. Diabetes care in the hospital 1. Glycemic targets in hospitalized patients 2. Anti-hyperglycemic agents in hospitalized patients 3. Preventing hypoglycemia 4. Diabetes care providers in the hospital 5. Self-management in the hospital 6. Diabetes self-management education in the hospital 7. Medical nutrition therapy in the hospital 8. Bedside blood glucose monitoring 9. Discharge planning IX. STRATEGIES FOR IMPROVING DIABETES CARE, p. S46