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Report for Clinical Trial NCT00588172

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Genetic Variation in OCT1 and Response to Metformin

Type 2 diabetes its microvascular and macrovascular complications have become a major global health problem. Metformin is often used as first-line therapy for this disorder given that it is cheap, may cause weight loss and does not have significant side-effects in healthy patients. On the other hand, as many as one third of all patients with type 2 diabetes initially treated with metformin never achieve a meaningful response to this intervention. Recently, genetic variation in the organic cation transporter 1 (Oct1) gene which encodes a protein, OCT1, mediating metformin uptake by the liver, its primary site of action, has been shown alter metformin action. In Oct1-deficient mice the glucose-lowering effects of metformin are completely abolished. Moreover a polymorphism with a 20% minor allele frequency in Caucasians also alters the effect of metformin on glucose tolerance (the net result of glucose uptake and glucose release) after ingestion of 75g of glucose. However, it is unknown if this polymorphism affects suppression of endogenous glucose production or stimulation of peripheral glucose uptake by metformin, or both, and to what degree. We propose to utilize established methodology to measure glucose turnover in response to a mixed meal to determine how common genetic variation in OCT1 alters response to metformin in healthy volunteers. This will clarify the effect of these variants on response to metformin in humans. The knowledge gained from this study will help to design future studies examining the role of OCT1 genotype in determining initial therapy for type 2 diabetes.

NCT00588172 Type 2 Diabetes
MeSH:Diabetes Mellitus, Type 2
HPO:Type II diabetes mellitus

1 Interventions

Name: Metformin

Description: 1000mg bid for 1 week
Type: Drug
Group Labels: 2

1 2


Primary Outcomes

Measure: Change in glucose area under the curve after a mixed meal in response to metformin

Time: before and after 1 week of metformin

Secondary Outcomes

Measure: Change in glucose disappearance and suppression of endogenous glucose production in response to metformin

Time: before and after 1 week of metformin therapy

Purpose: Basic Science

Allocation: Non-Randomized

Parallel Assignment


There are 4 SNPs

SNPs


1 G174S

Inclusion criteria: - 1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function. --- R61C --- --- G401S --- --- G465R --- --- G174S ---


2 G401S

Inclusion criteria: - 1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function. --- R61C --- --- G401S ---


3 G465R

Inclusion criteria: - 1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function. --- R61C --- --- G401S --- --- G465R ---


4 R61C

Inclusion criteria: - 1. Heterozygous or homozygous for the nsSNPs R61C, G401S, 420Del, G465R, G174S (see supplementary info (3)) or without any nsSNPs that could potentially alter gene function. --- R61C ---



HPO Nodes


HPO: