What you carry at this position in your DNA and what research says about it.
Type 2 Diabetes Risk: 10/10 evidence, 105 publications.
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Sample genotype (not yours): C/C
Typical Risk of Type 2 Diabetes
This genotype is associated with typical blood sugar levels and a standard baseline risk for type 2 diabetes. It lacks the risk-elevating T allele, making it the most favorable genotype for metabolic health at this locus.
What this genotype means: Typical blood sugar regulation; Standard baseline risk of type 2 diabetes; Slightly higher average body mass index.
Sample genotype (not yours): C/T
Increased Risk of Type 2 Diabetes
Carrying one copy of the T allele is associated with a moderately increased risk of developing type 2 diabetes. It can lead to slightly higher blood sugar levels and reduced insulin secretion.
What this genotype means: Moderately increased risk of type 2 diabetes; Slightly reduced insulin secretion; Slightly higher fasting blood sugar levels.
Sample genotype (not yours): T/T
Significantly Increased Risk of Type 2 Diabetes
Carrying two copies of the T allele is linked to a roughly twofold increase in type 2 diabetes risk. This genotype is associated with impaired insulin secretion and higher fasting blood sugar.
What this genotype means: Nearly doubled risk of type 2 diabetes; Impaired insulin secretion and sensitivity; Higher average fasting blood sugar and HbA1c.
Gene function and biological role
Gene Function: The TCF7L2 gene encodes a transcription factor that plays a critical role in the Wnt signaling pathway [1]. This pathway is essential for the development, survival, and proper function of pancreatic beta cells [1]. TCF7L2 helps regulate glucose metabolism by coordinating the expression of genes involved in insulin secretion [2]. Alterations in this gene can impair the body's ability to release insulin in response to glucose, leading to elevated blood sugar levels [2]. It is widely recognized as one of the most significant genetic determinants of type 2 diabetes risk in the human genome [3].
Variant Impact: This variant, rs7903146, is located in an intron of the TCF7L2 gene and acts as a key regulatory modifier of gene expression [4]. The change from a C to a T allele alters the chromatin structure in pancreatic islets, leading to increased expression of TCF7L2 [5]. This overexpression paradoxically impairs insulin secretion and reduces the insulin-releasing effects of incretin hormones [2]. Consequently, carriers of the T allele exhibit reduced first-phase insulin secretion and higher hepatic glucose production [2]. It represents the strongest single common genetic risk factor discovered for type 2 diabetes [3].
Key Insight: The risk variant paradoxically links a lower average body weight with a higher risk of developing type 2 diabetes.
Location: TCF7L2. Chromosome 10 · 10q25.2 · 113.0 Mb
Estimated prevalence by population
Global 53.0%; European 50.1%; African 50.0%; East Asian 94.7%; South Asian 48.4%; Americas 54.0%; Ashkenazi 50.8%; Finnish 65.9%; Middle Eastern 35.4%; Amish 53.6%.
Estimated CC genotype frequency.
Global 39.2%; European 41.3%; African 41.4%; East Asian 5.2%; South Asian 42.3%; Americas 38.9%; Ashkenazi 40.9%; Finnish 30.5%; Middle Eastern 48.2%; Amish 39.2%.
Estimated CT genotype frequency.
Global 7.8%; European 8.5%; African 8.6%; East Asian 0.1%; South Asian 9.3%; Americas 7.0%; Ashkenazi 8.2%; Finnish 3.5%; Middle Eastern 16.4%; Amish 7.2%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Diabetes & Glycemic Traits
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. Typical Risk.
Blood Glucose. Evidence: 9/10. Source: PMID 34059833. Typical.
Obesity & Body Composition
Body Mass Index. Evidence: 10/10. Source: PMID 25673413. Slightly Higher.
Hypertension
Blood Pressure. Evidence: 9/10. Source: PMID 30578418. Typical.
Heart Disease
Coronary Artery Disease. Evidence: 8/10. Source: PMID 35915156. Typical Risk.
Endocrine & Reproductive
Pregnancy & Birth Complications
Gestational Diabetes. Evidence: 8/10. Source: PMID 35220425. Typical Risk.
Showing effects for C/T genotype
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. ~1.4x Higher Risk.
Blood Glucose. Evidence: 9/10. Source: PMID 34059833. Slightly Higher.
Body Mass Index. Evidence: 10/10. Source: PMID 25673413. Typical.
Blood Pressure. Evidence: 9/10. Source: PMID 30578418. Slightly Higher.
Coronary Artery Disease. Evidence: 8/10. Source: PMID 35915156. Slightly Increased.
Gestational Diabetes. Evidence: 8/10. Source: PMID 35220425. Slightly Increased.
Showing effects for T/T genotype
Type 2 Diabetes. Evidence: 10/10. Source: PMID 17293876. ~2x Higher Risk.
Blood Glucose. Evidence: 9/10. Source: PMID 34059833. Higher.
Body Mass Index. Evidence: 10/10. Source: PMID 25673413. Slightly Lower.
Blood Pressure. Evidence: 9/10. Source: PMID 30578418. Higher.
Coronary Artery Disease. Evidence: 8/10. Source: PMID 35915156. Increased Risk.
Gestational Diabetes. Evidence: 8/10. Source: PMID 35220425. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having two copies of the C allele means carrying the baseline genetic profile for this highly studied metabolic locus [1]. This genotype is associated with normal insulin secretion and typical sensitivity to incretin hormones, which help regulate blood sugar after meals [2]. Consequently, individuals with this profile have a significantly lower risk of developing type 2 diabetes and gestational diabetes compared to those carrying the T allele [3]. While this genotype is protective against diabetes, some studies suggest it is associated with a slightly higher body mass index (BMI) [4]. This paradox occurs because the diabetes-promoting T allele is linked to a leaner body profile but poorer pancreatic function [4]. Maintaining a balanced diet and regular exercise remains highly effective for supporting metabolic health with this genotype [5].
Typical blood sugar regulation; Standard baseline risk of type 2 diabetes; Slightly higher average body mass index.
Sample genotype: CT (Heterozygous)
Carrying a single copy of the T allele is associated with a moderate increase in the risk of developing type 2 diabetes, estimated at roughly 1.4 times the baseline [1]. This genetic variant impairs the pancreatic beta cells' ability to secrete insulin efficiently in response to glucose [2]. It also reduces the body's sensitivity to incretin hormones, which are crucial for signaling insulin release after eating [3]. Over time, this can lead to slightly elevated fasting blood sugar and HbA1c levels [4]. Interestingly, carriers of this allele may have a slightly lower average body mass index (BMI) despite the higher diabetes risk, a phenomenon linked to altered fat storage [5]. Clinical studies show that lifestyle modifications, such as adopting a Mediterranean diet, can significantly mitigate the cardiovascular and metabolic risks associated with this genotype [6]. Additionally, individuals with this genotype may respond differently to certain diabetes medications, showing better responses to metformin but poorer responses to sulfonylureas [3].
Moderately increased risk of type 2 diabetes; Slightly reduced insulin secretion; Slightly higher fasting blood sugar levels.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele confers the highest genetic risk at this locus, nearly doubling the likelihood of developing type 2 diabetes [1]. This genotype is strongly associated with impaired insulin secretion from pancreatic beta cells and reduced sensitivity to incretins [2]. Individuals with this profile often exhibit higher fasting glucose and HbA1c levels, as well as an increased risk of gestational diabetes [3]. The genetic effect is highly consistent across diverse global populations [4]. Despite the elevated risk of diabetes, this genotype is paradoxically associated with a slightly lower body mass index (BMI) due to altered adipose tissue biology [5]. Lifestyle interventions are highly impactful for individuals with this profile; a randomized trial demonstrated that a Mediterranean diet rich in healthy fats can completely offset the elevated stroke and cardiovascular risks associated with this variant [6]. Pharmacogenomic research also indicates that carriers may experience a poorer therapeutic response to sulfonylurea medications but a highly favorable response to metformin [7].
Nearly doubled risk of type 2 diabetes; Impaired insulin secretion and sensitivity; Higher average fasting blood sugar and HbA1c.
Variants with shared genetic architecture
rs34872471 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
rs7901695 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
rs4506565 · TCF7L2 Gene · Chr 10 · Type 2 Diabetes Risk
Alterations in TCF7L2 expression define its role as a key regulator of glucose metabolism.
Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes.
A genome-wide association study identifies novel risk loci for type 2 diabetes.
A map of open chromatin in human pancreatic islets.
HMGB1 binds to the rs7903146 locus in TCF7L2 in human pancreatic islets.
Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals.
The trans-ancestral genomic architecture of glycemic traits.
Content updated August 2026.
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