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Huang, Chunmei

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Huang

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Chunmei

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Huang, Chunmei
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    The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH): Design of a pharmacogenetic Resource for Type 2 Diabetes
    (Public Library of Science, 2015) Walford, Geoffrey A.; Colomo, Natalia; Todd, Jennifer; Billings, Liana K.; Fernandez, Marlene; Chamarthi, Bindu; Warner, A. Sofia; Davis, Jaclyn; Littleton, Katherine R.; Hernandez, Alicia M.; Fanelli, Rebecca R.; Lanier, Amelia; Barbato, Corinne; Ackerman, Rachel J.; Khan, Sabina Q.; Bui, Rosa; Garber, Laurel; Stolerman, Elliot S.; Moore, Allan F.; Huang, Chunmei; Kaur, Varinderpal; Harden, Maegan; Taylor, Andrew; Chen, Ling; Manning, Alisa; Huang, Paul; Wexler, Deborah; McCarthy, Rita M.; Lo, Janet; Thomas, Melissa K.; Grant, Richard W.; Goldfine, Allison B.; Hudson, Margo; Florez, Jose
    Objective: Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. Methods: All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. Results: Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. Conclusions: SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. Trial Registration ClinicalTrials.gov NCT01762046
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    Pharmacogenetics in Type 2 Diabetes: Potential Implications for Clinical Practice
    (BioMed Central, 2011) Huang, Chunmei; Florez, Jose
    Pharmacogenetic research aims to study how genetic variation may influence drug efficacy and/or toxicity; pharmacogenomics expands this quest to the entire genome. Pharmacogenetic findings may help to uncover new drug targets, illuminate pathophysiology, clarify disease heterogeneity, aid in the fine-mapping of genetic associations, and contribute to personalized treatment. In diabetes, there is precedent for the successful application of pharmacogenetic concepts to monogenic forms of the disease, such as maturity onset diabetes of the young or neonatal diabetes. Whether similar insights will be produced for the common form of type 2 diabetes remains to be seen. With recent advances in genetic approaches, the successive application of candidate gene studies, large-scale genotyping studies and genome-wide association studies has begun to generate suggestive results that may lead to changes in clinical practice. However, many potential barriers to the translation of pharmacogenetic discoveries to the clinical management of diabetes still remain. Here, we offer a contemporary overview of the field in its current state, identify potential obstacles, and highlight future directions.