R230C and C230C Variants of ABCA1 and Glyburide Response

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes

Treatments: Drug: Glyburide

Study type: Interventional

Funder types: Other

Identifiers

NCT01456650

INNSZ-ABCA1

Details and patient eligibility

About

The objective of the study is to know if the R230C and C230C variants of the ATP-binding cassette transporter A1 (ABCA1) gene are associated with a smaller glucose lowering effect compared to the wild type allele (R230R) in patients with type 2 diabetes.

Full description

Specific objectives:

1. In patients with type 2 diabetes stratified by the existence of the risk alleles (R230C/C230C) or the wild variant (R230R) of ABC-A1, compare the changes resulting from the treatment with glibenclamide on following continuous variables:

   • Fasting glucose
   • Percentage reduction
   • Hemoglobin A1c,
   • Cholesterol, triglycerides, HDL cholesterol, LDL cholesterol
   • Weight

2. In patients with type 2 diabetes stratified by the existence of the risk alleles (R230C/C230C) or the wild variant (R230R) of ABC-A1, compare the changes resulting from the treatment with glibenclamide on following binomial variables:

   • Number of cases that reach fasting plasma glucose lower than 110 mg/dl
   • Number of cases that reach an HbA1c less than 7%

Enrollment: 85 patients

Sex: All

Ages: 20 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults 20 to 79 years
• Body mass index >18 and 39.9 ≤
• Men or women
• Mexicans mestizos.
• Moderate hyperglycemia (126 to 250 mg/dl and HbA1c levels between 7 and 10%) despite being treated with a dietary program in combination or not with metformin (2 g/d).

Exclusion criteria

• Patients with chronic complications of diabetes: ischemic heart disease, stroke, proliferative retinopathy or blindness, albuminuria, chronic diarrhea, gastroparesis, non-traumatic amputation of lower limbs.
• Patients with any monogenic syndrome, obesity, diabetes or hypoalphalipoproteinemia
• Patients with acquired diseases that produce secondarily obesity or diabetes.
• Treatment with anorexigenics or accelerate weight loss at the time of the selection.
• Cardiovascular event in the 6 months prior to study entry.
• Steroids, chemotherapy, immunosuppressive or radiotherapy.
• Infections or concurrent acute diseases.
• Catabolic diseases such as cancer or AIDS
• Pregnancy

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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85 participants in 1 patient group

Glyburide

Experimental group

Description:

Patients in which the fasting glucose persisted above the treatment goal (fasting glucose \<126 mg/dl) after a 4 week diet period will receive glyburide. The dose of the medication will be adjusted based on the results of fasting glucose values. At each visit patients will return the leftover tablets; counts of the tablets will be the method for measuring the adherence to treatment. The medical study participants who decided to doses of glibenclamide will not know the allele of ABCA1 gene under study.

Treatment:

Drug: Glyburide