Study design
This was a single center, randomized, double blind, placebo-controlled trial comparing pre and post effects of GA versus placebo in diabetic patients who have agreed to participate in this trial.
The trial was conducted at Academy Charity Teaching Hospital (ACTH) in Sudan; it took place from August 2014 to February 2015. All patients had been diagnosed with type 2 diabetes mellitus according to the criteria of WHO [14].
The trial protocol was approved by the local ethical committee of State of Khartoum Ministry of Health –and it is registered under PACTR201403000785219. This study was conducted according to the guidelines of the Declaration of Helsinki. Informed consent was obtained from all patients.
Outcomes
Primary outcome
The primary outcome was assessed in our previous article which was the effect of GA on mean percent change of fasting plasma glucose and HbA1c from baseline level [15].
Secondary outcome
Secondary outcomes included in our previous article were changes of GA on BMI and lipid profile [15]. In this study secondary outcomes included are obesity anthropometric indexes (VAI, BAI, LAP and deep abdominal adipose tissue (DAAT) and mean percent change of systolic and diastolic blood pressure from baseline level.
Recruitment
Patients were recruited from diabetes clinic at ACTH, Khartoum (Fig. 1). Those referred to the clinic were offered the opportunity to participate in this trial. The initial screening visit included the signing of the consent form, filling of questionnaire, and measurement of weight, height, waist circumference, hip circumference, blood pressure and blood sample for biochemical test. Patients were instructed to fast for 10–12 h prior to their first visit.
A total of 100 type 2 diabetic patients agreed to take part and signed the consent forms after the purpose and instructions concerning the trial had been explained to them. Patients with type 2 diabetes mellitus and on anti-hyperglycemic medication with fasting plasma glucose of (FPG) ≥7.0 mmol/L (126 mg/dl) and HbA1c ≥ 6.5% were included.
Alcoholics or drug addicts, patients with history of gastrointestinal diseases or Gum Arabic allergy, type 1 diabetes mellitus, pregnancy or planning to have a child within next 6 months and patients not eligible for the study due to medical reason evaluated by physician were excluded [15].
Randomization and blinding
Randomization was done by series of numbers generated by independent third-party not associated with the study. Patients and chief attending doctor were blind to the intervention. Supplement package of GA or placebo (pectin) were prepared in sealed boxes. Pectin was chosen as placebo because it is a soluble polysaccharide with viscous sensation when dissolved in water similar to GA. It is a good source of fiber and has been recommended for diabetics.
The daily supplement was a 30 g of powdered GA (Dar Savanna Ltd., Khartoum, Sudan) or 5 g of placebo (Andre Pectin, Yantani, China). The high viscosity of pectin limits consumption of it to 5 g only, 250 mL of water was mixed well with the package content before intake. No dietary restrictions were given and patients were asked not to change their lifestyle or physical activities during the study period. Patients continued taking their medications as prescribed by the physician.
Consumption of supplements and any of adverse reactions were examined by attending doctor. Lifestyle and medication of each patient was checked using a self-reporting sheet. Participants were followed weekly and the final examination was completed after 3 months of intervention [15].
Intervention
Of the 100 patients who were enrolled in the research, 97 were given either placebo (n = 47) or GA (n = 50). Ninety-one completed the study, three patients violated the instructions and were advised to discontinue; two got pregnant and one patient had a traffic accident and was hospitalized.
Data collection and measurements
Baseline measurements for all patients were taken, and they included; anthropometric, blood pressure measurements, blood samples for fasting plasma glucose (FPG), HbA1c and lipid profiles, in addition to completing a general health questionnaire. Blood samples were obtained by venipuncture kept in cryogenic collection tubes and were centrifuged immediately at 2700 rpm for 10 min to separate serum from blood. The serum was used to determine lipid profile (HDL and triglyceride levels). Enzymatic biochemical analyses were performed using (BioSystems S.A. 310- Semi automated chemistry analyser) to determine lipid profile; HDL and LDL were analyzed by using precipitation and cholesterol oxidase method, FPG was analysed by using glucose oxidase method and HbA1c by direct ion exchange method [15]. Waist circumference was measured by using flexible, elastic measuring tape at midpoint between the lower rib and the top of iliac crest at the end of expiration. Hip circumference was measured at the level of the greater femoral trochanters. The waist circumference divided by the hip circumference gave the (waist-to-hip ratio (WHR). Body weight (kg) was measured on calibrated balance scale and height (cm) was measured with standmeter to nearest 0.5 cm, BMI was calculated as the ratio of weight in kilograms to height in meters squared (kg/m2) [16].
Lipid accumulation product (LAP) was calculated with the following formula: male LAP = [waist (cm)-65] X TG (mmol/l) and female LAP = [waist (cm) -58] X TG (mmol/l) [17], and VAI was calculated from [WC/ (39.68 + 1.88 x BMI)] x (TG/1.03) x (1.31/HDL) for men and [WC/ (36.58 + 1.89 x BMI] x (TG/0.81) x (1.52/HDL) for women [18].
Body Adiposity Index (BAI) was calculated by using hip circumference and height (BAI = hip circumference (cm) divided by (height (m)) 1.5 minus 18) [11].
Deep abdominal adipose tissue (DAAT) was calculated by using the formula: − 382.9 + [1.09 x weight - (kg)] + [6.04 x WC- (cm)] + (− 2.29 x BMI) for men and − 278 + [− 0.86 x weight - (kg)] + [5.19 x WC- (cm)] for women [16].
Blood pressure (BP) was measured using mercury sphygmomanometer.
Visceral adipose index (VAI) and blood pressure (BP) were measured as primary outcome measures, HC, WC, WHR, BMI, BAI, LAP, DAAT, HDL-c and triglyceride were evaluated and measured as secondary outcomes. These measurements were performed before and after intervention.
Data analysis
Statistical analyses were performed using SPSS (Statistical Package for the Social Science, IBM SPSS version 23) values were expressed as mean ± standard deviation and Paired sample T-Test was used to compare continuous variables or Pearson’s chi-square test within the groups. P < 0.05 was regarded as statistically significant.