Pioglitazone and Metformin in Diabetic Children

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.

Inclusion criteria

• Pediatric patients with type 2 diabetes according to ADA.
• Patients who have not previously received anti-diabetic treatment or have been treated solely with diet and exercise or have received only one anti-diabetic agent, and who have not applied insulin within 1 month of study start.
• HbA1c between >6.5% and <10%.
• Stable body weight at least 3 months before study start.
• No intense exercise.
• Free of other infectious, chronic, or acute inflammatory processes in the 3 months prior to study.
• Previous informed consent signed (both children and parents or guardians).
• Either sex
• 8-17 years old.

Exclusion criteria

• Personal history of type 1 diabetes
• Chronic renal failure or serum creatinine over 1.0 mg/dl.
• Active hepatic disease (ALT and AST 3 times normal)
• Heart conditions
• Acute or chronic metabolic acidosis
• Receiving steroids or insulin