The Health Influences of Puberty (HIP) Study
Condition: Obesity; Insulin Resistance; Gonadal Dysfunction; Type 2 Diabetes
MeSH terms: Obesity; Insulin Resistance; Gonadal Disorders
Intervention: Metformin; Placebo
Intervention description: After randomization, the study drug (metformin or placebo) is gradually titrated to full dose of 1000 mg BID (or to maximum tolerated, at least 500 mg BID) over a period of 4 weeks to minimize adverse gastrointestinal effects. Participants are seen every three months to measure compliance and dispense new study drug. Every 6 months, they also have a physical examination in order to determine puberty staging. Study measurements (IVGTT, bloodwork, DXA) are performed at Tanner 4 puberty and Tanner 5 (puberty completion), at which time the study drug is stopped. Study measurements will be performed again 6 months after study drug is completed to assess if effects are persistent after study drug is stopped. During the treatment period, all participants receive standard lifestyle counseling.; Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 104.0
Sex: All
Minimum age: 9 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Insulin resistance; Puberty; Obesity; Hypogonadism; Gonadal dysfunction; Metformin

Summary:

      The Health Influences of Puberty (HIP) Study is designed to explore the relationships between
      puberty and the onset of type 2 diabetes in adolescents. The results of this study will help
      us better understand how to prevent type 2 diabetes in these youth. Children go through many
      changes during puberty, including important hormonal and behavioral alterations. Among these
      changes, it has long been known that, during puberty, insulin does not work as well as it
      does before and after puberty. This is called physiologic insulin resistance. In healthy
      children, this does not cause diabetes or affect blood sugar in any way because the body is
      able to compensate by making more insulin. Indeed, this is thought to be an important part of
      the adolescent growth spurt. However, in some children with increased risk for developing
      type 2 diabetes due to obesity and genetics, the worsening insulin resistance of puberty
      cannot be compensated for and these youth get diabetes early. The investigators believe this
      is because type 2 diabetes is rarely, if ever, seen before puberty begins, and the peak of
      diabetes onset in adolescents occurs at the time of the worst insulin resistance. This
      specific research project has two goals: 1. To examine effects of obesity on how well the
      body's insulin works during puberty, and 2. To see if treatment of obese children during this
      critical period of puberty with a medication that improves insulin resistance (metformin)
      will help prevent early onset type 2 diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  BMI ≥ 95th percentile

          -  At least Tanner 2, but no more than Tanner 3

          -  Age ≥ 9 years

          -  Absence of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or Type 2
             diabetes mellitus (T2DM)

        Exclusion Criteria:

          -  Presence of T2DM, IGT or IFG

          -  Any disorder or medication known to effect glucose tolerance;

          -  Hypertension or hyperlipidemia requiring pharmacological intervention;

          -  Weight >300lbs. due to limits of imaging tables.

          -  Chronic illness