Melatonin is a hormone that regulates the circadian cycle in addition to having an antioxidant effect. Patients with prediabetes state, has a deregulation of glucose metabolism and an overproduction of reactive oxygen species caused by levels of hyperglycemia that generate DNA modification in pancreatic beta cells, which leads to apoptosis and a deficient production of insulin. The administration of metformin and melatonin could be a possibility to treat and reverse the prediabetic state decreasing the glycemic levels and reactive oxygen species production.
A randomized, double blind, placebo-controlled, pilot clinical trial will carried out in 42 patients with a diagnosis of prediabetes, according to the American Diabetes Association criteria. The patients will be divide in three groups administrating metformin plus placebo, melatonin plus placebo or melatonin plus metformin. The intervention will be with 500 mg lengthed release tablets of metformin once a day in the morning, per 90 days, 5 mg lengthed release capsules of melatonin one a day in the night per 90 days and calcined magnesia as a placebo. Before and after the intervention, will be evaluate: fasting plasma glucose, blood glucose after an oral glucose tolerance test, A1c hemoglobin fraction, micronuclei frequency, nuclear anomalies frequency, insulin secretion and insulin sensitivity, weight, height, body mass index, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid, and sleep quality.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
42
The administration of melatonin will be indicated at night before bedtime to avoid alterations of the circadian cycle. It will be contained in bottles labeled "Medication 2" to maintain the masking. This intervention will be indicated in two groups (Melatonin plus metformin and Melatonin plus placebo)
For the intervention with metformin, prolonged-release tablets will be used to reduce adverse effects and improve adherence to treatment. It will be contained in bottles labeled "Medication 1" to maintain masking. This intervention will be indicated in two groups (Melatonin plus metformin and metformin plus placebo)
The placebo may be contained in bottles labeled "Medication 1" or "Medication 2" depending on the time of administration, and the group in which it is used. Placebo will be used in two groups (Melatonin plus placebo and Metformin plus placebo)
Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara
Guadalajara, Jalisco, Mexico
RECRUITINGFasting plasma glucose (FPG)
The FPG will be evaluate in a blood sample after a 8 - 12 hour fasting period. Will be use a fotometric quantification of glucose levels in plasma sample and will report in mg/dL.
Time frame: Baseline to week 12
Blood Glucose level after an Oral Glucose tolerance Test
Will estimate the glucose levels at 2 hours after administration of 75 grams of anhydrid dextrosa. The result will report in mg/dL.
Time frame: Baseline to week 12
A1c Hemoglobin Fraction (HbA1C)
HbA1c will be measured with High-performance liquid chromatography technique from a blood sample. The result will report in percentage (%).
Time frame: Baseline to week 12
Micronuclei frequency
The frequency of micronuclei will be measured from a cytological sample obtained from the oral epithelium by careful scraping of both cheeks. A fluorescence technique will be performed using acridine orange, as well as a Giemsa-Wrigth stain. The result will be reported in micronucleus frequency per 1000 cells.
Time frame: Baseline to week 12
Nuclear anomalies frequency
The nuclear anomalies frequency will be measured from a cytological sample obtained from the oral epithelium by careful scraping of both cheeks. A fluorescence technique will be performed using acridine orange, as well as a Giemsa-Wrigth stain. They will be divided according to their morphology (multinucleated cells, pyknotic nucleus, karyorrhexis, caryolysis, nuclei buds, condensed chromatin) and will be reported by the number of findings per 1000 cells.
Time frame: Baseline to week 12
Body height
It will be determined using the electric bioimpedance scale with electrical stadiometer. The measurement will be made with the patient standing on the marks on the bioimpedance scale, in an upright position. This determination will be reported in meters (m) with a minimum precision of 0.01 meters.
Time frame: Baseline to week 12
Body weight
t will be determined using the electric bioimpedance scale with electrical stadiometer. The measurement will be made with the patient standing on the marks on the bioimpedance scale, in an upright position. This determination will be reported in kilograms (Kg).
Time frame: Baseline to week 12
Body mass index
The calculation will be made using the results of the weight, and height. From these results will be calculated by dividing the weight obtained over the square of the height. This index will be reported in kilograms per square meter (kg / m2)
Time frame: Baseline to week 12
Insulin Secretion
The calculation will be made using the insulogenic index, using the values obtained in the oral glucose tolerance test, and determining the insulin levels in plasma at 120 minutes and at the baseline measurement, as well as the glucose levels obtained at the 120 minutes and at the baseline measurement.
Time frame: Baseline to week 12
Baseline Insulin Secretion
It will be use the Stumvoll index for the calculation of this parameter.
Time frame: Baseline to week 12
Insulin sensitivity
For the calculation of this parameter the Matsuda index will be used, from the values obtained and applying the formula.
Time frame: Baseline to week 12
Total Cholesterol
The determination of total cholesterol will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Time frame: Baseline to week 12
High-density lipoprotein (HDL)
The determination of HDL will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Time frame: Baseline to week 12
Low-density lipoprotein
LDL will be calculated using the Friedewald formula from the results obtained of total cholesterol, HDL and triglycerides. The result will be expressed in milligrams per deciliter (mg / dl).
Time frame: Baseline to week 12
Triglycerides
The determination of triglycerides will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in milligrams per deciliter (mg / dL).
Time frame: Baseline to week 12
Serum Lactate
The determination of serum lactate will be made from a blood sample with the patient fasting between 8 to 12 hours. Samples will be analyzed by spectrophotometry. The result will be reported in millimoles per Liter (mg / dL).
Time frame: Baseline to week 12
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