Observational Study to Assess Glycosylated Hemoglobin Changes After 6 Months of Treatment With Pioglitazone.

Study Overview
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Brief Summary
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The purpose of this study is to asses changes in glycosylated hemoglobin, fasting blood lipids and genetic polymorphism's in peroxisomal proliferator activated receptors--gamma receptor after 6 months of pioglitazone, once daily (QD), treatment.

Detailed Description
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The metabolic control in type 2 diabetes mellitus can be measured by means of glycosylated hemoglobin. A low value glycosylated hemoglobin indicates a good metabolic control, and has been shown to be associated with a better prognosis regarding diabetic complications. Type 2 diabetes is a disease with a profound genetic component. Peroxisome proliferator-activated receptor gamma is a transcription factor implicated in adipocyte differentiation, lipid and glucose metabolism. Peroxisome proliferator-activated receptor alfa is a transcription factor implicated in lipid oxidation and gluconeogenesis and is present in liver, kidney, heart, skeletal muscle and adipose tissue. Pioglitazone is a thiazolidinedione that targets nuclear peroxisomal proliferator activated receptors, members of the super family of ligand activated transcription factors. Specifically, thiazolidinediones bind to the peroxisome proliferator-activated receptor gamma and affect transcription factors that influence expression of genes responsible for the production of proteins important in carbohydrate and lipoprotein metabolism. These include increases in glucose transporters 1 and 4 resulting in enhanced peripheral glucose utilization by fat and skeletal muscle. This is a pharmacoepidemiological study to evaluate whether the individual genotype of the patients have any influence on the efficacy of pioglitazone.

Official Title
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A Prospective Study of Associations of Changes in HbA1C and Fasting Blood Lipids Due to Treatment With Pioglitazone for 6 Months and Genetic Polymorphism's in PPAR-gamma

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Pioglitazone and sulphonylurea
* Drug: Pioglitazone and sulphonylurea
* Drug: Pioglitazone and metformin
* Drug: Pioglitazone and metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfills all requirements for treatment with pioglitazone. Willing to start treatment with pioglitazone. Exclusion Criteria: Has previously participated in this study. Is currently taking or have taken oral antidiabetic medications other than sulfonylurea or metformin within the last 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pioglitazone 15 mg QD + Sulphonylurea<br> | Drug: Pioglitazone and sulphonylurea<br>* Pioglitazone 15 mg, tablets, orally, once daily and stable sulphonylurea therapy for up to 24 months.<br>* Other names: AD4833;|
| Pioglitazone 30 mg QD + Sulphonylurea<br> | Drug: Pioglitazone and sulphonylurea<br>* Pioglitazone 30 mg, tablets, orally, once daily and stable sulphonylurea therapy for up to 24 months.<br>* Other names: AD4833;|
| Pioglitazone 15 mg QD + Metformin<br> | Drug: Pioglitazone and metformin<br>* Pioglitazone 15 mg, tablets, orally, once daily and stable metformin therapy for up to 24 months.<br>* Other names: AD4833;|
| Pioglitazone 30 mg QD + Metformin<br> | Drug: Pioglitazone and metformin<br>* Pioglitazone 30 mg, tablets, orally, once daily and stable metformin therapy for up to 24 months.<br>* Other names: AD4833;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glycosylated hemoglobin. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Clinical Laboratory Tests (alanine transaminase, hematocrit and hemoglobin). |  | End of Treatment | 
| Change from baseline in Body Weight. |  | End of Treatment | 
| Percentage of treatment responders defined as a patient with 0.6% decrease in HbA1C from baseline visit to final visit or accomplishment of a HbA1c value at or below 6.5%. |  | End of Treatment | 
| Change from baseline in beta-cell function (Homeostasis model assessment). |  | End of Treatment | 
| Change from baseline in insulin resistance (Homeostasis model assessment). |  | End of Treatment | 
| Change from baseline in fasting lipoproteins (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein-cholesterol and triglycerides). |  | End of Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy