Genetic Risk Assessment for Type 2 Diabetes

Recruiting at 1 trial location

Overseen By Esther Oyerinde

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must not be taking: Steroids, Metformin, Anti-diabetics, others

Disqualifiers: Diabetes, Pregnancy, Chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals without diabetes but with a high genetic risk for type 2 diabetes exhibit signs of insulin resistance and glucose tolerance issues. Participants will consume a sugary beverage, and researchers will test their body's response over four hours. This research targets individuals with a high BMI (a measure of body fat based on height and weight) who have participated in specific biobanks for future research. As an unphased trial, it offers a unique opportunity to contribute to understanding diabetes risk factors and prevention strategies.

Will I have to stop taking my current medications?

If you are taking medications that affect glucose and insulin response, like steroids or metformin, you may need to stop them to participate in this trial.

What prior data suggests that this protocol is safe?

Research shows that using genetic risk scores to understand type 2 diabetes is safe for participants. Past studies have not found any safety issues with identifying genetic risk for type 2 diabetes. No major side effects have been reported from determining these genetic risk scores in people.

The study includes a standard oral glucose tolerance test, where participants drink a sugary beverage, and a whole-body DXA scan, which checks bone density. Both procedures are commonly used and generally well-tolerated. The sugary drink might cause mild discomfort, like an upset stomach, in some people, but this is rare.

Overall, previous research has safely managed the assessment of genetic risk for type 2 diabetes using these methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's diving into genetic risk assessment for type 2 diabetes in a way that current treatments don’t. Instead of focusing on managing blood sugar levels with medications like metformin or insulin, this approach uses phenotyping to understand an individual's genetic predisposition to the disease. By conducting a detailed glucose tolerance test and a whole-body DXA scan, researchers hope to gather insights that could lead to more personalized and effective prevention strategies in the future. This trial could pave the way for more tailored interventions, reducing the reliance on a one-size-fits-all approach.

What evidence suggests that phenotyping genetic risk for type 2 diabetes is effective for assessing glucose tolerance and insulin resistance?

Research shows that people with a higher genetic risk for type 2 diabetes often struggle to control their blood sugar levels. Their bodies have difficulty managing sugar effectively. One study found that a higher genetic risk correlated with poorer results in tests measuring how well the body processes sugar after eating. These tests include the oral disposition index and insulinogenic index, which assess insulin function. Another study suggests that identifying these genetic risks can help predict the likelihood of developing diabetes. Understanding these genetic factors can offer insights into preventing or managing type 2 diabetes before it fully develops. Participants in this trial will undergo phenotyping to assess their genetic risk for type 2 diabetes, including a four-hour frequently sampled oral glucose tolerance test and a whole body DXA. ^{1 6 7 8 9}

Who Is on the Research Team?

Jessica R Wilson, MD, MS

Principal Investigator

University of Pennsylvania

Lorraine Levitt Katz, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for individuals aged 10-70, with adults having a BMI of 25 or higher and children in the 85th percentile for BMI. Participants must have previously joined the UPenn or Center for Applied Genomics Biobank and agreed to future contact. It's not open to those with diabetes, anemia, recent chemotherapy, certain metabolic disorders, on medications affecting glucose/insulin response like steroids or metformin, pregnant women, people with acute illness impacting insulin/glucose dynamics, gastrointestinal issues affecting absorption or major illnesses requiring regular medication.

Inclusion Criteria

I am between 10 and 70 years old.

You have been part of a specific biobank in the past and agreed to be contacted for future research.

My BMI is 25 or higher as an adult, or in the 85th percentile or higher as a child/adolescent.

Exclusion Criteria

I have recently undergone chemotherapy.

Pregnancy

I have had stomach or intestine problems or surgery affecting how I absorb medicine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phenotyping

Participants undergo a four-hour frequently sampled oral glucose tolerance test and a whole body DXA scan

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the phenotyping procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phenotyping Genetic Risk for Type 2 Diabetes

Trial Overview

The study investigates if non-diabetic individuals at high genetic risk for type 2 diabetes show impaired glucose tolerance and insulin resistance compared to those at low risk. Participants will consume a standard glucose beverage (75g) followed by tests including DXA scans and whole-body assessments.

How Is the Trial Designed?

Group I: Phenotyping Experimental Treatment 2 Interventions

All participants will undergo a four-hour frequently sampled oral glucose tolerance test in which they will ingest a 75g glucose beverage (intervention) within five minutes and have samples collected at baseline and for four hours after. They will also undergo a whole body DXA (intervention) during the study day.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Despite the discovery of numerous genetic factors linked to type 2 diabetes since 2000, these factors only account for a small portion of the overall inherited risk, limiting their effectiveness in personalizing treatment.

Current genetic markers do not significantly enhance individual risk prediction compared to standard clinical assessments, although they may help identify specific subgroups for targeted prevention strategies, which still require further evaluation for effectiveness and cost-efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic susceptibility to type 2 diabetes and implications for therapy. Florez, JC.[2021]

Over 70 genetic loci are linked to the risk of developing type 2 diabetes (T2D), suggesting that genetic information could help identify individuals at risk earlier.

While including genetic data in risk models shows some improvement in reclassification, the benefits are currently too modest for practical clinical application, indicating a need for further research before genetics can be reliably used for early T2D prediction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of genetic information in the prediction of Type 2 diabetes. Drenos, F.[2019]

Genetic testing can identify at least 1% of individuals with diabetes who have monogenic forms, allowing for personalized treatment that improves glucose control and prognosis.

Identifying genetic variants related to diabetes can lead to novel treatment approaches and better risk assessment for families, highlighting the importance of integrating genetic research into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized medicine in diabetes mellitus: current opportunities and future prospects. Kleinberger, JW., Pollin, TI.[2018]

Type 2 diabetes can be divided into five distinct subtypes, each with different genetic backgrounds and risks for complications, as shown by a study involving individuals from the Swedish ANDIS study and replicated in Finnish studies.

The severe insulin-resistant subtype is specifically linked to genetic factors related to fasting insulin levels, while a unique genetic variant is associated with mild obesity-related diabetes, highlighting the importance of genetic differences in understanding diabetes progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes. Mansour Aly, D., Dwivedi, OP., Prasad, RB., et al.[2022]

In a study of 2,751 participants, incorporating single nucleotide polymorphisms (SNPs) related to fasting glucose, insulin, lipids, and obesity into a genetic risk score significantly improved the ability to distinguish between individuals with and without type 2 diabetes, achieving a discriminative power (ROC AUC) of 0.626.

The model that included all relevant SNPs outperformed the conventional type 2 diabetes genetic risk score, which had a discriminative power of 0.591, highlighting the importance of considering multiple metabolic traits in diabetes risk assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population. Fontaine-Bisson, B., Renström, F., Rolandsson, O., et al.[2022]

A genetic risk score (GRS) based on 14 specific genetic variants was found to be significantly associated with type 2 diabetes in a study of 1,487 Japanese individuals, indicating its potential as a predictive tool for the disease.

The β-cell function-related GRS was linked to important clinical features in diabetes patients, such as the need for insulin therapy and reduced β-cell function, suggesting it could help identify patients who may benefit from more aggressive treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals. Iwata, M., Maeda, S., Kamura, Y., et al.[2022]

In a study of 5,535 initially healthy individuals over 10 years, common genetic variants associated with type 2 diabetes did not effectively distinguish between those who developed the disease and those who did not, with genetic models showing lower discrimination compared to established non-genetic risk models.

The addition of genetic information to existing phenotype-based risk models provided only a slight improvement in predicting type 2 diabetes risk, suggesting that while genetic insights are valuable for understanding the disease, they do not significantly enhance risk assessment compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. Talmud, PJ., Hingorani, AD., Cooper, JA., et al.[2022]

Genome-wide association studies (GWAS) have significantly advanced our understanding of the genetic factors contributing to type 2 diabetes, explaining about 10% of the disease's heritability and highlighting the importance of β-cell dysfunction.

These studies have not only confirmed previous epidemiological findings but also identified new biological pathways that could serve as potential targets for future diabetes treatments and pharmacogenetic trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The genetics of type 2 diabetes: what have we learned from GWAS? Billings, LK., Florez, JC.[2021]

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