Novel Biomarker for Development of T2D

Diabetes Type II Clinical Trial

Official title:

A Novel Biomarker for Development of Type 2 Diabetes: 11Beta-Hydroxy Steroid Dehydrogenase Type 1 Activity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02326129
• Other study ID #: Pro00057460
• Secondary ID: K23DK117067
• Status: Completed
• Start date: February 2015
• Est. completion date: April 5, 2023

Study information

• Verified date: August 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators wants to determine if 11β-HSD1 activity will be positively associated, and 5α-reductase activity negatively associated, with (a) degree of insulin resistance defined by the homeostatic model assessment of insulin resistance index (HOMA-IR) and (b) worsening glycemic control defined by higher HbA1c and impaired fasting glucose in a group of obese children and young adults with or without type 2 diabetes compared to lean children and young adults without diabetes. The investigators also want to identify key metabolic signatures associated with diabetes using metabolomic profiling.

Description:

The overarching hypothesis is that increases in whole body 11β-HSD1 activity precede and presage the development of type 2 diabetes (T2D) in high-risk obese adolescents, serving as a critical determinant of insulin resistance and glucose intolerance. The increase in 11β-HSD1 activity, in combination with decreases in 5α-reductase activity, will increase tissue cortisol production, promoting the development of insulin resistance and the metabolic syndrome and predisposing to T2D. The investigators predict that increases in 11β-HSD1 activity will be detected in obese children prior to the development of insulin resistance and glucose intolerance and that the progressive increases in 11β-HSD1 will correlate with progressive decreases in insulin sensitivity and glucose tolerance. Given preliminary findings, the investigators also predict that increases in 11β-HSD1 will be greater and occur earlier in development in males than females. This could establish 11β-HSD1 activity as a novel, non-invasive biomarker for progression to, or for development of, glucose intolerance and T2D. The identification of 11β-HSD1 as a biomarker that predicts T2D would have critical clinical import, allowing us to identify obese children and adults at highest risk of metabolic decompensation. Studies of 11β-HSD1 in obese subjects with varying degrees of IR and glucose intolerance will also narrow critical gaps in the understanding of the pathogenesis of T2D. The investigators would like to also validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance. To that end the investigators would like to examine detailed metabolomic profiles in 24 hour and spot urine samples. The study population will include 50 obese adolescents with T2D, 50 obese adolescents without T2D and 50 age, gender, race and pubertal status-matched normal weight controls. The subjects will be recruited at the Healthy Lifestyle Program at Duke, Diabetes Clinics at Lenox Baker Children's Hospital and Roxboro Clinics. Study activities include physical exam and medical history, vitals, laboratory tests (only for obese adolescents), urine testing for sugar (only for normal weight adolescents), 24 hour urine collection, spot urine collection, body fat content measurement, and food and activity questionnaire.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: April 5, 2023
• Est. primary completion date: April 5, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

Inclusion criteria:

1. Obese/Overweight adolescents/young adults without T2D who are having their first visit to the Healthy Lifestyle Program at Duke or Obese/Overweight adolescents/young adults without T2D recruited from the community at PBRC

2. Obese/Overweight adolescents/young adults with prediabetes (HbA1c between 5.7-6.4%) and T2D (HbA1c=6.5%)followed at Diabetes Clinics or recruited from the community at PBRC

3. Age, gender, race and pubertal status matched normal weight adolescents presenting for "well child check" at Roxboro Clinics

4. =12 to 21 (inclusive) years of age for urine studies

5. 18-21 years of age obese adolescents/young adults without T2D and age, gender, race and pubertal status matched normal weight controls for OGTT sub-study

6. Both the subject and one parent/guardian present will need to be able to speak and read English

Exclusion criteria:

1. Currently or within the past month taken systemic or inhaled corticosteroids, antipsychotics, medications for weight loss, topiramate, acute use of contraceptives (less than 3 months) or medroxy-progesterone acetate, medications to treat ADHD

2. Children with any genetic syndrome

3. Children with decompensated hypothyroidism (treated with levothyroxine and a TSH >10 µIU/mL )

4. Normal weight children (BMI percentile 5%-<85%) with glucosuria, as defined by a positive urine glucose dip stick test

5. Children and young adults who self report that they are pregnant (pregnancy is excluded in both the main and sub-study)

6. Proteinuria, as defined by protein level equal to or above 300 mg/dl (+++) on a urine dip stick test.

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Diabetes Type II

Locations

Country	Name	City	State
United States	Pennington Biomedical Research center	Baton Rouge	Louisiana
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Duke University	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	Children's Miracle Network, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relationship between 11ß-HSD1 and 5a-reductase activity, and measures of insulin resistance	To assess the relationship between 11ß-HSD1 and 5a-reductase activity, and measures of insulin resistance in a cohort of obese children with varying degrees of insulin resistance and glucose intolerance	One year
Primary	Gender and pubertal status	Investigate the role of gender and pubertal status on 11ß-HSD1 and 5a-reductase activity	One year
Primary	Compare 11ß-HSD1 activity and 5a-reductase activity among obese adolescents with T2D, obese adolescents without T2D and normal weight controls	The investigators hypothesize that obese adolescents with T2D will have the highest levels of 11ß-HSD1 activity followed by the obese adolescents with insulin resistance, followed by obese subjects with normal insulin sensitivity. Normal weight control group will have the lowest levels.	One year
Secondary	Relationship between 11ß-HSD1 and 5a-reductase activity, and key metabolic signatures associated with insulin resistance	The investigators hypothesize that 11ß-HSD1 activity will be positively associated, and 5a-reductase activity negatively associated, with key metabolic signatures associated with insulin resistance.	One year
Secondary	Urine metabolic signatures associated with insulin resistance and type 2 diabetes	The investigators would like to validate if urine metabolomic profiling can be used for identifying key metabolomic signatures associated with insulin resistance	One year
Secondary	Spot urine for metabolic profiling	The investigators hypothesize that they will identify the same key metabolomic signatures associated with insulin resistance in obese adolescents with T2D compared to obese adolescents without T2D, and normal weight control group in spot fasting am urine samples.	One year
Secondary	Metabolic signatures correlate with parameters of glucose tolerance	To determine if urinary metabolic signatures correlate with parameters of glucose tolerance in normal weight controls and obese adolescents without T2D, and glycemic control in obese subjects with T2D.	One year