Genetic Risk Assessment for Type 2 Diabetes
Recruiting in Palo Alto (17 mi)
+1 other location
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Pennsylvania
Must not be taking: Steroids, Metformin, Anti-diabetics, others
Disqualifiers: Diabetes, Pregnancy, Chemotherapy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study tests the hypothesis that non-diabetic individuals with a high genetic risk score for type 2 diabetes have impaired glucose tolerance and insulin resistance compared to those with a low genetic risk score for type 2 diabetes.
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 data supports the effectiveness of the treatment Phenotyping Genetic Risk for Type 2 Diabetes?
Research suggests that genetic risk scores, which use genetic information, may help identify individuals at higher risk for developing type 2 diabetes early on. However, the improvements in predicting who will develop diabetes using these scores are currently modest and not yet strong enough for clinical use.
12345Is the genetic risk assessment for type 2 diabetes safe for humans?
The research articles do not provide specific safety data for the genetic risk assessment for type 2 diabetes, but they focus on understanding genetic factors and improving prediction and treatment strategies.
34567How is the treatment 'Phenotyping Genetic Risk for Type 2 Diabetes' different from other treatments for type 2 diabetes?
This treatment is unique because it uses genetic risk scores to assess an individual's susceptibility to type 2 diabetes, potentially allowing for earlier identification and personalized monitoring, unlike traditional treatments that focus on managing symptoms after diagnosis.
13458Eligibility Criteria
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.
+1 more
Exclusion Criteria
I have recently undergone chemotherapy.
Pregnancy
I have had stomach or intestine problems or surgery affecting how I absorb medicine.
+7 more
Trial Timeline
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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: PhenotypingExperimental Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
Childrens Hospital of PhiladelphiaPhiladelphia, PA
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
References
Genetic susceptibility to type 2 diabetes and implications for therapy. [2021]Since 2000, we have witnessed an explosion of known genetic determinants of type 2 diabetes risk. These findings have seeded the expectation that our ability to make personalized, predictive, therapeutic clinical decisions is imminent. However, the loci discovered to date explain only a small fraction of overall inheritable risk for this disease. In many cases, the reported associations merely signal regions of the genome that are overrepresented in disease versus health but do not identify the causal variants. Well-powered cohort studies have shown that the set of markers detected thus far does not significantly improve individual risk prediction or stratification over common clinical variables, with the possible exception of younger subjects. On the other hand, risk genotypes may help target subgroups for more intensive surveillance or prevention efforts, although whether such a strategy improves patient outcomes and/or is cost-effective should be examined. Similarly, whether genetic information will help guide therapeutic decisions must be tested in adequately designed and rigorously conducted clinical trials.
Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. [2022]To assess the performance of a panel of common single nucleotide polymorphisms (genotypes) associated with type 2 diabetes in distinguishing incident cases of future type 2 diabetes (discrimination), and to examine the effect of adding genetic information to previously validated non-genetic (phenotype based) models developed to estimate the absolute risk of type 2 diabetes.
Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population. [2022]We determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score.
The use of genetic information in the prediction of Type 2 diabetes. [2019]Type 2 diabetes (T2D) is a metabolic disorder characterized by high blood glucose levels and elevated risk of cardiovascular events. The progression of T2D can be delayed, or prevented, so early prediction is of high importance. More than 70 genetic loci are associated with T2D risk, raising the possibility of early identification of future cases. Results show that the benefits in discrimination by including genes in current risk models are uncertain. Improvements have been shown in reclassification but are too modest for clinical use. Given the current guidelines for T2D risk assessment and the increasing availability of genotyped individuals, we could soon be able to use genetics, not to quantify risk, but to inform clinicians on those requiring earlier observation.
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. [2022]We evaluated the clinical usefulness of a genetic risk score (GRS) based on 14 well-established variants for type 2 diabetes.
Personalized medicine in diabetes mellitus: current opportunities and future prospects. [2018]Diabetes mellitus affects approximately 382 million individuals worldwide and is a leading cause of morbidity and mortality. Over 40 and nearly 80 genetic loci influencing susceptibility to type 1 and type 2 diabetes, respectively, have been identified. In addition, there is emerging evidence that some genetic variants help to predict response to treatment. Other variants confer apparent protection from diabetes or its complications and may lead to development of novel treatment approaches. Currently, there is clear clinical utility to genetic testing to find the at least 1% of diabetic individuals who have monogenic diabetes (e.g., maturity-onset diabetes of the young and KATP channel neonatal diabetes). Diagnosing many of these currently underdiagnosed types of diabetes enables personalized treatment, resulting in improved and less invasive glucose control, better prediction of prognosis, and enhanced familial risk assessment. Efforts to enhance the rate of detection, diagnosis, and personalized treatment of individuals with monogenic diabetes should set the stage for effective clinical translation of current genetic, pharmacogenetic, and pharmacogenomic research of more complex forms of diabetes.
The genetics of type 2 diabetes: what have we learned from GWAS? [2021]Type 2 diabetes mellitus has been at the forefront of human diseases and phenotypes studied by new genetic analyses. Thanks to genome-wide association studies, we have made substantial progress in elucidating the genetic basis of type 2 diabetes. This review summarizes the concept, history, and recent discoveries produced by genome-wide association studies for type 2 diabetes and glycemic traits, with a focus on the key notions we have gleaned from these efforts. Genome-wide association findings have illustrated novel pathways, pointed toward fundamental biology, confirmed prior epidemiological observations, drawn attention to the role of β-cell dysfunction in type 2 diabetes, explained ~10% of disease heritability, tempered our expectations with regard to their use in clinical prediction, and provided possible targets for pharmacotherapy and pharmacogenetic clinical trials. We can apply these lessons to future investigation so as to improve our understanding of the genetic basis of type 2 diabetes.
Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes. [2022]Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diabetes; the Finnish DIREVA (Diabetes register in Vasa) and Botnia studies were used for replication. We show that subtypes differ with regard to family history of diabetes and association with GRS for diabetes-related traits. The severe insulin-resistant subtype was uniquely associated with GRS for fasting insulin but not with variants in the TCF7L2 locus or GRS reflecting insulin secretion. Further, an SNP (rs10824307) near LRMDA was uniquely associated with mild obesity-related diabetes. Therefore, we conclude that the subtypes have partially distinct genetic backgrounds indicating etiological differences.