Faculty

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Richard M Watanabe, PhD
Professor of Preventive Medicine
Preventive Medicine
CSC 2250 Alcazar St Health Sciences Campus Los Angeles
+1 323 442 2053

Overview

I have a primary interest in the pathophysiology and genetics of type 2 diabetes mellitus. My research program focuses on genetics, pathophysiology (and the correlation with genetics), and mathematical modeling of physiologic systems.

In the area of complex disease genetics, I am focusing on both positional cloning of susceptibility genes for type 2 diabetes and diabetes-related traits and understanding the gene-phenotype relationships and how they are impacted by environmental exposures.

Publications

Postprandial effect to decrease soluble epoxide hydrolase activity: roles of insulin and gut microbiota. J Nutr Biochem. 2017 Jul 21; 49:8-14. View in: PubMed

Plasminogen Activator Inhibitor-1 Predicts Negative Alterations in Whole-Body Insulin Sensitivity in Chronic HIV Infection. AIDS Res Hum Retroviruses. 2017 Jul; 33(7):723-727. View in: PubMed

A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes. 2017 Mar 24. View in: PubMed

Genetic regulatory signatures underlying islet gene expression and type 2 diabetes. Proc Natl Acad Sci U S A. 2017 Feb 28; 114(9):2301-2306. View in: PubMed

Improved Performance of Dynamic Measures of Insulin Response Over Surrogate Indices to Identify Genetic Contributors of Type 2 Diabetes: The GUARDIAN Consortium. Diabetes. 2016 Jul; 65(7):2072-80. View in: PubMed

The genetic regulatory signature of type 2 diabetes in human skeletal muscle. Nat Commun. 2016 Jun 29; 7:11764. View in: PubMed

Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans. Diabetes Care. 2016 Apr; 39(4):547-54. View in: PubMed

The genetic architecture of type 2 diabetes. Nature. 2016 08 04; 536(7614):41-47. View in: PubMed

An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes. Endocrinology. 2015 Sep; 156(9):3147-56. View in: PubMed

Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium. Diabetes. 2015 May; 64(5):1853-66. View in: PubMed

Adults with long-duration type 2 diabetes have blunted glycemic and ß-cell function improvements after bariatric surgery. Obesity (Silver Spring). 2015 Mar; 23(3):523-6. View in: PubMed

Variation in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes. J Clin Endocrinol Metab. 2015 Mar; 100(3):1187-95. View in: PubMed

A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). PLoS One. 2015; 10(11):e0134649. View in: PubMed

Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus. PLoS Genet. 2015 Jan; 11(1):e1004876. View in: PubMed

High calorie intake is associated with worsening insulin resistance and ß-cell function in Hispanic women after gestational diabetes mellitus. Diabetes Care. 2014 Dec; 37(12):3294-300. View in: PubMed

Antiretroviral therapy modifies the genetic effect of known type 2 diabetes-associated risk variants in HIV-infected women. AIDS. 2014 Jul 31; 28(12):1815-23. View in: PubMed

Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans. Diabetologia. 2014 Jul; 57(7):1391-9. View in: PubMed

Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes. 2014 Jun; 63(6):2158-71. View in: PubMed

Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans. Obesity (Silver Spring). 2014 Apr; 22(4):1157-64. View in: PubMed

Longitudinal changes in insulin sensitivity and beta cell function between women with and without a history of gestational diabetes mellitus. Diabetologia. 2013 Dec; 56(12):2753-60. View in: PubMed

Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care. 2013 Aug; 36(8):2175-82. View in: PubMed

High-fat diet is associated with obesity-mediated insulin resistance and ß-cell dysfunction in Mexican Americans. J Nutr. 2013 Apr; 143(4):479-85. View in: PubMed

Self-reported physical activity is associated with ß-cell function in Mexican American adults. Diabetes Care. 2013 Mar; 36(3):638-44. View in: PubMed

Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat Genet. 2013 Feb; 45(2):197-201. View in: PubMed

Metabolic syndrome is linked to chromosome 7q21 and associated with genetic variants in CD36 and GNAT3 in Mexican Americans. Obesity (Silver Spring). 2012 Oct; 20(10):2083-92. View in: PubMed

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012 Sep; 44(9):991-1005. View in: PubMed

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012 May 13; 44(6):659-69. View in: PubMed

Estimating hepatic glucokinase activity using a simple model of lactate kinetics. Diabetes Care. 2012 May; 35(5):1015-20. View in: PubMed

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels. Diabetes. 2012 May; 61(5):1291-6. View in: PubMed

Pancreatic iron and glucose dysregulation in thalassemia major. Am J Hematol. 2012 Feb; 87(2):155-60. View in: PubMed

Deterioration in cardiometabolic risk markers in obese women during depot medroxyprogesterone acetate use. Contraception. 2012 Jan; 85(1):36-41. View in: PubMed

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012; 8(3):e1002607. View in: PubMed

A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012; 7(1):e29202. View in: PubMed

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes. 2011 Oct; 60(10):2624-34. View in: PubMed

A better index of body adiposity. Obesity (Silver Spring). 2011 May; 19(5):1083-9. View in: PubMed

Drugs, diabetes and pharmacogenomics: the road to personalized therapy. Pharmacogenomics. 2011 May; 12(5):699-701. View in: PubMed

Inherited destiny? Genetics and gestational diabetes mellitus. Genome Med. 2011 Mar 25; 3(3):18. View in: PubMed

A principal components-based clustering method to identify variants associated with complex traits. Hum Hered. 2011; 71(1):50-8. View in: PubMed

Statistical issues in gene association studies. Methods Mol Biol. 2011; 700:17-36. View in: PubMed

The genetics of insulin resistance: Where's Waldo? Curr Diab Rep. The genetics of insulin resistance: Where's Waldo? Curr Diab Rep. 2010 Dec; 10(6):476-84. View in: PubMed

A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010 Dec; 92(6):1359-68. View in: PubMed

Limitations in surrogate measures of insulin resistance. J Clin Endocrinol Metab. 2010 Nov; 95(11):4874-6. View in: PubMed

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010 Nov; 42(11):937-48. View in: PubMed

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet. 2010 Nov; 42(11):949-60. View in: PubMed

Pharmacogenetics of Anti-Diabetes Drugs. Pharmaceuticals (Basel). 2010 Aug 01; 3(8):2610-2646. View in: PubMed

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010 Jul; 42(7):579-89. View in: PubMed

Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. Diabetes. 2010 May; 59(5):1266-75. View in: PubMed

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010 Feb; 42(2):105-16. View in: PubMed

Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010 Feb; 42(2):142-8. View in: PubMed

A principal-components-based clustering method to identify multiple variants associated with rheumatoid arthritis and arthritis-related autoantibodies. BMC Proc. 2009 Dec 15; 3 Suppl 7:S129. View in: PubMed

Additive effects of genetic variation in GCK and G6PC2 on insulin secretion and fasting glucose. Diabetes. 2009 Dec; 58(12):2946-53. View in: PubMed

Evidence for sex-specific associations between variation in acid phosphatase locus 1 (ACP1) and insulin sensitivity in Mexican-Americans. J Clin Endocrinol Metab. 2009 Oct; 94(10):4094-102. View in: PubMed

Obesity attenuates the contribution of African admixture to the insulin secretory profile in peripubertal children: a longitudinal analysis. Obesity (Silver Spring). 2009 Jul; 17(7):1318-25. View in: PubMed

Variation in IGF2BP2 interacts with adiposity to alter insulin sensitivity in Mexican Americans. Obesity (Silver Spring). 2009 Apr; 17(4):729-36. View in: PubMed

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009 Jan; 41(1):25-34. View in: PubMed

Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009 Jan; 41(1):77-81. View in: PubMed

Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat Genet. 2009 Jan; 41(1):82-8. View in: PubMed

OGTT-derived measures of insulin sensitivity are confounded by factors other than insulin sensitivity itself. Obesity (Silver Spring). 2008 Aug; 16(8):1938-45. View in: PubMed

Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest. 2008 Jul; 118(7):2620-8. View in: PubMed

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008 May; 40(5):638-45. View in: PubMed

Evidence of interaction between PPARG2 and HNF4A contributing to variation in insulin sensitivity in Mexican Americans. Diabetes. 2008 Apr; 57(4):1048-56. View in: PubMed

Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008 Feb; 40(2):161-9. View in: PubMed

Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet. 2008 Feb; 40(2):198-203. View in: PubMed

Prioritized subset analysis: improving power in genome-wide association studies. Hum Hered. 2008; 65(3):129-41. View in: PubMed

Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes. Diabetes. 2007 Dec; 56(12):3027-32. View in: PubMed

What is gestational diabetes? Diabetes Care. What is gestational diabetes? Diabetes Care. 2007 Jul; 30 Suppl 2:S105-11. View in: PubMed

Genetics of gestational diabetes mellitus and type 2 diabetes. Diabetes Care. 2007 Jul; 30 Suppl 2:S134-40. View in: PubMed

A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun 01; 316(5829):1341-5. View in: PubMed

Reduction in added sugar intake and improvement in insulin secretion in overweight latina adolescents. Metab Syndr Relat Disord. 2007 Jun; 5(2):183-93. View in: PubMed

Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans. Diabetes. 2007 May; 56(5):1481-5. View in: PubMed

Subsets of Finns with high HDL to total cholesterol ratio show evidence for linkage to type 2 diabetes on chromosome 6q. Hum Hered. 2007; 63(1):17-25. View in: PubMed

Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes. 2007 Jan; 56(1):256-64. View in: PubMed

Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes. 2006 Sep; 55(9):2534-40. View in: PubMed

Impact of ABCB1 (MDR1) haplotypes on tacrolimus dosing in adult lung transplant patients who are CYP3A5 *3/*3 non-expressors. Transpl Immunol. 2006 Jan; 15(3):235-40. View in: PubMed

Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns. Hum Genet. 2005 Nov; 118(2):245-54. View in: PubMed

Sequence variation in PPARG may underlie differential response to troglitazone. Diabetes. 2005 Nov; 54(11):3319-25. View in: PubMed

Ordered subset analysis in genetic linkage mapping of complex traits. Genet Epidemiol. 2004 Jul; 27(1):53-63. View in: PubMed

Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study. Diabetes Care. 2004 Jun; 27(6):1365-8. View in: PubMed

Acute alcohol consumption improves insulin action without affecting insulin secretion in type 2 diabetic subjects. Diabetes Care. 2004 Jun; 27(6):1369-74. View in: PubMed

Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes. 2004 Apr; 53(4):1141-9. View in: PubMed

A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14. Diabetes. 2004 Mar; 53(3):821-9. View in: PubMed

Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin. Diabetes. 2003 Aug; 52(8):2168-74. View in: PubMed

MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther. 2003; 5(6):1003-15. View in: PubMed

Insulin resistance and associated compensatory responses in african-american and Hispanic children. Diabetes Care. 2002 Dec; 25(12):2184-90. View in: PubMed

Variation in three single nucleotide polymorphisms in the calpain-10 gene not associated with type 2 diabetes in a large Finnish cohort. Diabetes. 2002 May; 51(5):1644-8. View in: PubMed

Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics. J Clin Endocrinol Metab. 2002 Mar; 87(3):1233-8. View in: PubMed

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