ABSTRACT

Aims/Introduction: Effectiveness of Diamel^® on the biochemical variables: fasting blood glucose, postprandial glucose, cholesterol, triglycerides, and glycosylated haemoglobin [HbA1c] in type 2 diabetic patients receiving insulin terapy. Diamel is a natural product composed of trace elements: amino acids, vitamins, cranberry extract, and lettuce extract that have been activated by means of a magnetization process. Materials and methods: Randomized, doubleblind, comparator-controlled clinical trial. A central randomization centre used computer generated tables to allocate treatments. 116 patients suffering from type 2 diabetes mellitus treated with insulin at the Diabetes Care Centre in Pinar del Rio (Cuba), were recruited and randomly. The subjects were separated into two groups: Group A (n = 59), who were administered Diamel and Group B (n = 57) using placebo. The clinical and biochemical variables were assessed for 24 weeks. Results: Two subjects were excluded from the Diamel treatment group during the clinical trial. From the statistical point of view, a significant drop in the levels of the baseline glucose, postprandial glucose, glycated haemoglobin, and triglycerides was observed in the group taking Diamel (Group A). There was observed an increase in insulin requirements and in waist circumference in the subjects of Group B. There was not reported any severe or serious adverse reactions during this clinical trial. Conclusion: Diamel (nutritional supplement) together with the administration of insulin in type 2 diabetic patients is useful to optimize the biochemical variables (baseline and postprandial glucose, Hb A_1C, plus triglycerides), as well as to prevent the increase of insulin requirements at medium-term.

1. Introduction

Almost 85% to 95% of whole diabetic population suffers from type 2 Diabetes Mellitus [1]. The interaction between genetic and environmental risk factors contributes to the development of this type of diabetes, as they can affect β-cell function and the peripheral insulin sensitivity [2-4]. New scientific advances state that pathophysiological changes of type 2 diabetes, in which oxidative stress has a major role, can now be treated [5,6]. The increase in free radicals inhibits the insulin action and contributes to the deterioration in β-cell function, leading to chronic complications [7-11]. Several authors have carried out studies on natural products having hopeful results [12-14]. The food supplement Diamel^®, from Catalysis, S. L. laboratories, is a natural product composed of trace elements: amino acids, vitamins, cranberry extract, and lettuce extract that have been activated by means of a magnetization process which enhances the biological properties of each of every component. Diamel works out on pancreas whereby its components―zinc, arginine and ornithine―help to stimulate the secretion of insulin, while the lettuce extract helps to reduce the gastrointestinal glucose absorption [15]. Cranberry extract is an effective antioxidant, a hypoglycemic and lipid-lowering agent, which improves β-cell function by reducing the harmful effects of free radicals [16,17]. Our clinical trial was carried out in order to assess how effective Diamel is on the main biochemical metabolic control variables (fasting blood glucose, postprandial glucose, cholesterol, triglycerides, glycosylated hemoglobin Hb A_1C) in type 2 diabetic subjects undergoing insulin treatment.

2. Material and Methods

2.1. Design

Randomized in two parallel groups, double-blind, controlled clinical trial. A central randomization centre used computer generated tables to allocate treatments.

2.2. Participants

116 patients were recruited and randomized. They were diagnosed as type 2 diabetes mellitus and were given a double dosage of intermediate-acting insulin. The patients were taking medical care in an out-patient unit and control at the Diabetic Care Centre in Pinar del Río province.

2.3. Eligibility

Patients included in the clinical trial met the following inclusion criteria: both genders, ages from 40 to 65, those suffering from type 2 diabetes for 0 - 15 years, calculated when they were first diagnosed, and those receiving the written informed consent to take part in the clinical trial. Those patients meeting the inclusion criteria but refusing to take part in the study or those who showed moderate to severe chronic complications, sepsis or having intercurrent diseases that could interfere with the clinical trial, some way, were excluded.

2.4. Settings

The study took place at the Diabetic Care Center and at “Abel Santamaría Cuadrado” University Hospital, in Pinar del Río province, Cuba, from October 2009 to April 2011.

2.5. Interventions

The subjects were given a double dosage of intermediate-acting insulin, they were randomly separated into two groups: Group A (n = 59), who were administered Diamel (two capsules of 660 mg before breakfast, lunch and dinner), and Group B (n = 57) using placebo in the same dosage (Control group). A central randomization centre used computer generated tables to allocate treatments the clinical and biochemical variables (baseline and postprandial glucose; Hb A_1C, cholesterol, and triglycerides) were assessed during six months in both groups. All the patients’ variables were assessed in baseline conditions; their biochemical and anthropometric values were determined. The patients received pieces of advice and counselling from dieticians and were asked to practice gentle and gradual physical activity (walk for 30 to 45 minutes), 3 or 4 times a week.

The components of Diamel are shown in the Table 1.

2.6. Outcomes

Primary Outcome Measures:

1) Difference in daily dosage of insulin at 24 weeks and the beginning of the study;

2) Difference in the levels of glycemia (fasting and postprandial) at 24 weeks and at the beginning of the study in adjusted doses;

3) Difference in the levels of HbA1c at 24 weeks and at the beginning of the study;

Secondary Outcome Measures:

1) Presence or not of hypoglycemic reactions levels or of major intensity during the 24 weeks of treatment.

2.7. Sample Size

The study was designed to a statistical power of 90%, to detect an absolute difference of 30% in proportions to reduce or maintain insulin requirements together with the improvement of blood glucose levels (50% in the Diamel group compared to 20% of the control group) bearing in mind a type 1 error of 0.05 and a type 2 error of 0.10; needing 116 patients to reach the statistical significance. A level of 5% for the statistical significance was considered to carry out the full analysis. The statistical analysis was preformed using SPSS Inc to Windows, version 15, Chicago IL.

2.8. Randomisation

For allocation of the participants, a computer-generated list of random numbers was used (ASAL system). Participants were randomly assigned following simple randomization procedures. Two treatment groups were conformed: an experimental group, with Diamel (Group A), and another control group with placebo (Group B). To each patient was assigned a treatment outline according to the aleatory list. The center was a group of sealed envelopes, one for each patient, with consecutively numbers containing the assignment of treatment. In each envelope a number was included and it was taken as the number of inclusion in the trial.

The randomization was carried out by the members of staff, who were not involved in administering the product or evaluating the patients. Determination of whether a patient was given a double dosage of intermediate-acting insulin or would be treated with Diamel or placebo was made by reference to a statistical series based on random sampling numbers. The details of the series were unknown by any of the investigators or by the co-ordinator. The assignment was carried out at blind by the investigators after the patient gathered the inclusion approaches and they granted the consent to participate in the study. The patient, investigators, data collectors or data analysts had not access to the randomization schedule.

The Diamel and placebo were in capsule form and identical in appearance, taste and smell. Both products (Diamel and placebo) were supplied by Catalysis, S. L. (Madrid, Spain). They were prepacked in bottles and consecutively numbered for each patient according to the randomization schedule. Each patient was assigned an order number and received the capsules in the corresponding prepacked bottle. The method of administration of both products was similar.

2.9. Statistical Methods

The baseline characteristics were summarised using absolute frequencies and percentages for the qualitative variables; average and standard deviation were used to summarise the information about quantitative variables. Chi-square test was used to assess the qualitative variable differences between the two groups; and the MannWhitney U-test was used to analyse the quantitative variables.

The Wilcoxon signed-rank test for paired samples was used to examine changes between the start and the end of treatment when assessing the primary and secondary efficacy variables. The differences between the groups were examined using Mann-Whitney U-test.

All significance tests and resulting p-values were twosided, with an alpha level of 0.05.

2.10. Ethics

The clinical trial was carried out in accordance with the ethical principles established in the Declaration of Helsinki. It was also approved by the Ethics Research Committee and the Scientific Board at “Abel Santamaría Cuadrado” University Hospital, Pinar del Río. All patients included signed the consent form to take part in the research programme.

3. Results

For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome. The analysis was made according to the aleatory list. The flow chart of the participants (Figure 1) shows what occurred in both groups. Two subjects were excluded from the Diamel treatment group during the clinical trial: one patient got

pregnant in the third month of treatment and the other was identified as being a carrier of diabetic nephropathy during the follow-up. In the control Group B (placebo) one patient was excluded from the clinical trial after being diagnosed with incipient, chronic hepatopathy. Ageeligible participants were recruited from November 2009 to April 2010. All the patients' variables were assessed in baseline conditions; their biochemical and anthropometric values were determined.

Table 2 contains the main biochemical and clinical variables in Group A (Diamel) and Group B (placebo) at the start of the clinical trial. No significant statistical differences were found between the two groups, which indicated that both groups were considered to be similar.