Clinical trial NCT03195400: Pathogenesis of Youth Onset Type 2 Diabetes and Prediabetes
Official title: Pathogenesis of Youth Onset Type 2 Diabetes and Prediabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: IGT - Impaired Glucose Tolerance
T2D
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2017-06-22
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be selected from the Yale Pediatric Obesity Clinic or from the existing cohort of subjects who have had Oral Glucose Tolerance Tests and genotyping. Subjects will be Pre IGT and IGT adolescents 12-18 years old with either the CC or TT genotype. 50 CC pre IGT/IGT obese patients and 50 TT pre IGT/IGT obese patients will be rectruited.

Brief summary: Type 2 Diabetes (T2D) in obese youth is often preceded by a prediabetic state called: Impaired Glucose Tolerance (IGT), which is associated with a pre-existing defect in insulin secretion. This study intends to determine if genetic factors are associated with defects in insulin secretion, the incretin system and hepatic insulin resistance in obese adolescents. The long-term goal of this study is to generate information on both the genetics as well as the pathophysiology of Type 2 Diabetes in Youth, which ultimately might guide the investigators towards better preventive and treatment avenues.

Detailed description: The Specific Aims of this study are:

Aim 1a. To delineate the effects of TCF7L2 rs7903146 on functional Beta-Cell Capacity in obese adolescents with Impaired Glucose Tolerance (IGT) and pre-IGT.

Aim 1b. To determine if the risk genotype in TCF7L2 is associated with worsening in beta cell function longitudinally, thereby affecting changes in glucose tolerance.

Aim 2. To examine the functional effect of the rs7903146 variant in the TCF7L2 gene on a) incretin effect in obese adolescents with IGT and pre-IGT.

Aim 3. To determine the functional effects of TCF7L2 rs7903146 SNP on hepatic glucose fluxes in obese adolescents with IGT and pre-IGT.

Eligibility criteria: Inclusion Criteria:

* Good general health, taking no medication on a chronic basis;
* Age 12 to 18 yrs, in puberty (girls and boys: Tanner stage II - IV),
* BMI (BMI \>85th%) indicating obesity,
* Girls who are menstruating must have a negative pregnancy test during the study and, when possible, be in the follicular phase during infusion study visits (The follicular phase will be identified according to the last menstrual period record and/or according to the oral contraceptive assumption schedule. The investigators will not perform ovulation testing or hormonal assays);
* Subject must have normal liver and kidney function, amylase and lipase levels.
* Pre-IGT or IGT
* TT or CC genotype.

Exclusion Criteria:

* Baseline creatinine \>1.0 mg;
* Pregnancy;
* Presence of endocrinopathies (e.g. Cushing syndrome);
* Cardiac, renal or pulmonary or other chronic illness;
* Adolescents with psychiatric disorder or with substance abuse history and taking the drugs that affect glucose metabolism, such as any form of steroids, antipsychotics, progesterone preparations, and others.

Primary outcomes:
measure: Glucose tolerance status
timeFrame: Baseline
measure: Genotype
timeFrame: Baseline
measure: Beta cell capacity
timeFrame: Baseline
measure: Incretin effect
timeFrame: 3weeks to 1 month post Baseline testing
measure: Beta cell function (longitudinally)
timeFrame: 2 years post Baseline
measure: Hepatic glucose fluxes
timeFrame: 2 months post baseline testing
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Sonia Caprio, MD
role: PRINCIPAL_INVESTIGATOR
References: