Pioglitazone and Metformin in Diabetic Children
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      HYPOTHESIS: Treatment with pioglitazone is more effective in reducing resistin concentrations
      and insulin resistance than metformin in children with Type 2 Diabetes (T2D).

      MATERIAL AND METHODS: Pediatric patients aged 8-17 with T2D as defined by the American
      Diabetes Association (ADA) were included, not under treatment or who had been treated
      exclusively with diet and exercise or who only received an anti-diabetic agent, as well as
      those with a history of insulin use who had not applied insulin within 1 month before the
      initial visit. History of T2D, hypertension, exercise, diet, age, gender and somatometry are
      recorded. A Blood sample is taken to determine HbA1c, glucose, insulin and resistin.

      STATISTICAL ANALYSIS: The percentual change over 4 weeks is analyzed for concentrations of
      resistin, insulin resistance. Changes are noted for weeks 12, 24, 36 and 48 for resistin
      concentrations, HbA1c and HOMA values. Baseline and final values are compared with a paired t
      test. Lineal or logarithmic regression analysis is used to evaluate the relationship between
      homeostasis model assessment of insulin resistance (HOMA-IR) and resistin concentrations. The
      statistical significance between variables is determined using ANOVA. The effect of
      confounding variables is analyzed with a test of co-variance analysis. Statistical
      significance is considered as p <0.05.
    

Detailed description: 
      At 2 weeks prior to study all subjects meet with a dietician and are instructed to consume a
      weight-maintaining diet containing 50% carbohydrate, 30% fat, and 20% protein. During the
      week prior to the start of pioglitazone or metformin treatment, all subjects come to the
      clinic after a 12 hr overnight fast for a clinical examination (body weight, height, waist
      and hip circumferences) and biochemical tests. All tests are done between 8 and 10 am. A
      general structured interview is conducted. A questionnaire is used to obtain information on
      demographic and socioeconomic aspects. Anthropometric measurements are obtained. Body weight
      is measured on a 140-kg capacity floor scale, with the child standing in the center of the
      scale. Height is obtained by use of the floor scale's stadiometer, with the child standing in
      the center of the scale. Height is measured to the nearest 0.5 cm. Body weight is measured
      recorded to the nearest 0.1 Kg. Body Mass Index (BMI) is calculated as weight (Kg) divided by
      height (m2). Abdominal circumference is measured to the nearest 0.1 cm at the level of the
      greatest frontal extension of the abdomen between the bottom of the rib cage and the top of
      the iliac crest. The equipment is regularly calibrated using reference samples provided by
      the manufacturer. Baseline measurement of resistin (method) and insulin concentration
      (method). At the same time, blood samples are taken for liver function tests, fasting plasma
      glucose, lipids, and HbA1c.

      All studies are performed at 08:00 h following a 10-12 h overnight fast. Following completion
      of these studies, subjects are randomized to start on pioglitazone or metformin, 15 mg/day
      and 850 mg respectively, for 4 weeks period, subjects return to the Clinical of Pediatric
      Endocrinology at 08:00 h, following an overnight fast, for measurement of fasting plasma
      glucose concentration, body weight, and blood pressure. Fasting plasma lipids (total
      cholesterol, triglyceride, HDL cholesterol, and LDL cholesterol) are measured . Fructosamine,
      HbA1c is measured during the initial and final week of pioglitazone or metformin treatment.
      Dietary adherence is reinforced. After 4 weeks of treatment, all subjects undergo a
      measurement of fasting plasma glucose, resistin, and insulin concentration.
    

Intervention name(s): Metformin; Pioglitazone
Intervention type(s): Drug; Drug
Intervention description(s): 850 mg of Metformin daily, increased to 1700 mg after 12 weeks, for the duration of the trial.; 15 mg of pioglitazone daily, increased to 60 mg after 12 weeks.
Other intervention name(s): Recommended diet and 30 minutes of exercise daily; Recommended diet and 30 minutes of exercise daily
Intervention MeSH terms: Metformin; Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Type 2 diabetes; Resistin; Inflammation; Insulin Resistance