Prediabetes is a term that refers to alterations in glucose homeostasis, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both, involving a higher risk of progression type 2 diabetes mellitus (T2DM). Dapagliflozin is a selective and reversible inhibitor of sodium-glucose type 2 (SGLT-2) co-transporter, which reduces renal glucose reabsorption and promotes the glucose excretion through urine, so that the blood glucose is improved in patients with T2DM. Although this mechanism is independent of insulin, there are evidence of improved secretion and insulin sensitivity, so it is interesting to assess these effects in patients with prediabetes, as potential therapy for treating such disorders and prevent progression to T2DM. The aim of this study is to evaluate the effect of Dapagliflozin on insulin secretion and insulin sensitivity in patients with prediabetes. The investigators hypothesis is that the administration of dapagliflozin improve insulin secretion and insulin sensitivity in patients with prediabetes.
A randomized, double-blind, placebo-controlled clinical trial in 24 patients with a diagnosis of prediabetes in accordance with the American Diabetes Association (ADA) without treatment. They will be assigned randomly two groups of 12 patients each to receive 10 mg of Dapagliflozin (Forxiga, Astra Zeneca) or placebo, one per day before breakfast during 12 weeks. There will be calculated Area Under the Curve of glucose and insulin, total insulin secretion (Insulinogenic index), first-phase of insulin secretion (Stumvoll index) and insulin sensitivity (Matsuda index). This protocol it's already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers. Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05. This protocol was approved by a local ethics committee and written informed consent will be obtained from all volunteers.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
10 mg, one per day before breakfast during 12 weeks.
one per day before breakfast during 12 weeks.
Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
Guadalajara, Jalisco, Mexico
Fasting Glucose
The fasting glucose levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12
Time frame: Fasting Glucose levels at week 12
Postprandial Glucose
Postprandial glucose will be evaluated after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12
Time frame: Postprandial Glucose levels at Week 12
First Phase of Insulin Secretion
The first phase of insulin secretion will be calculated with Stumvoll index and the entered values reflect the frst phase of insulin secretion at week 12. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. First phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'), the entered values reflect the first phase of insulin secretion
Time frame: First Phase of Insulin Secretion at Week 12
Total Insulin Secretion
Total insulin secretion will be calculated with insulinogenic index and the entered values reflect the total insulin secretion at week 12. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin/ΔABC glucose), the entered values reflect the total insulin secretion
Time frame: Total Insulin Secretion at Week 12
Insulin Sensitivity
Insulin sensitivity will be calculated with Matsuda index and the entered values reflect the insulin sensitivity at week 12. Matsuda Index value is used to indicate insulin resistance on diabetes. Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. The entered values reflect the insulin sensitivity
Time frame: Insulin Sensitivity at Week 12
Glycosylated Hemoglobin
Glycosylated hemoglobin will be evaluated by ELISA and the entered values reflect the glycosylated hemoglobin at week 12
Time frame: Glycosylated Hemoglobin at Week 12
Body Weight
The body weight will be measured with a bioimpedance balance and the entered values reflect the body weight at week 12
Time frame: Body Weight at Week 12
Body Mass Index
Body Mas Index will be calculated with the Quetelet index formula and the entered values reflect the body mass index at week 12
Time frame: Body Mass Index at Week 12
Total Cholesterol
Total cholesterol levels will be evaluated by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12
Time frame: Total Cholesterol levels at Week 12
Triglycerides
Triglycerides levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12
Time frame: Triglycerides levels at Week 12
High Density Lipoprotein Cholesterol (HDL-c)
HDL-c levels will be evaluated with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12
Time frame: HDL-c levels at Week 12
Alanine Aminotransferase (ALT)
ALT levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time frame: ALT levels at Week 12
Aspartate Aminotransferase (AST)
AST levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time frame: AST levels at Week 12
Creatinine
Creatinine levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time frame: Creatinine levels at Week 12
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Uric Acid
Uric acid levels will be evaluated with enzymatic/colorimetric techniques at week 12
Time frame: Uric Acid levels at Week 12
Systolic Blood Pressure
Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time frame: Systolic Blood Pressure at Week 12
Diastolic Blood Pressure
Systolic Blood pressure will be measured with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time frame: Diastolic Blood Pressure at Week 12