Effects And Mechanism Of Propolis On Energy Metabolism And Oxidative Stress Of Patients With Type2 Diabetes

ObjectivesDiabetes mellitus(DM) is a group of metabolic diseases characterized by hyperglycemia. The prevalence of DM is increasing rapidly, which is one of the major public health problems in the world. Type 2 diabetes(T2D) is the most common type of DM. It is not only due to genetics, environment, lifestyle and diet, but thought to be related to oxidative stress as well. In this study, DM patients were treated with propolis based on a dietary survey and health analysis. After that, biochemical parameters were measured, including fasting plasma glucose(FPG), Hemoglobin A1c(Hb A1c), Lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), ferric-reducing antioxidant power(FRAP), malondialdehyde(MDA), total polyphenols, total flavonoids, oxidized low density lipoprotein(ox-LDL), carbonyls, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α). This study aims to investigate the effects and mechanism of propolis on energy metabolism and oxidative stress of T2 D patients.MethodsPart 1 Survey and analysis on diet of patients with T2D1. A food frequency questionnaire(FFQ) was designed for DM patients and conducted a cross-sectional study. In the meanwhile, a database for DM patients was set up.2. Lifestyle, dietary habit and some general characteristics(e.g. gender, age, BMI, education background, economic status) were added to the questionnaire in order to summarize the relationship between nutrient intake and general characteristics.3. Dietary nutrient intakes of T2 D patients were compared with recommended nutritional intakes(RNIs) or average intakes(AIs).4. Biological parameters were measured, including FPG, Hb A1 c, total protein, albumin, total cholesterol, high density lipoprotein cholesterol, urea nitrogen, uric acid and creatinine.Part 2 Effects and mechanism of propolis on energy metabolism and oxidative stress of patients with type 2 diabetes1. sixty-five qualified T2 D were randomized into two groups, i.e. control group and propolis group. Patients of propolis group took propolis capsules(2 capsules per time, 3 times/day) for 18 weeks. During intervention, a dietary survey was conducted. They were followed up 4 times to improve their compliance.2. Anthropometric parameters were measured before and after the experiment, including height, weight, body mass index(BMI), waist, hip, waist to hip ratio(WHR). BMI was calculated by weight(kg)/ height(m) 2 and WHR was calculated by waist(cm)/ hip(cm).3. Blood samples were collected before and after the experiment. Biological parameters were measured, including FPG, Hb A1 C, aldose reductase, adiponectin, LDH, GSH, SOD, FRAP, MDA, total polyphenols, total flavonoids, ox-LDL, IL-1β, IL-6, TNF-α as well as glutathione peroxidase(GSH-px), SOD,FRAP and MDA.ResultsPart 1 Survey and analysis on diet of patients with T2D1. There were 338 T2 D patents(177 males and 161 females) in this cross-sectional study, aged between 32 and 90(62.1± 11.2). There were 36 newly diagnosed patients. The average medical history was 10.1 years. 71% of the patients were overweight or obesity. 75.4% of the patients had never been to the college. 44.4% of the patients earned less than 5000 yuan per month.2. The daily intakes of energy, protein, fat, thiamin, riboflavin, niacin, phosphorus, potassium, magnesium, zinc, selenium and manganese by males were significantly higher than females(P< 0.05).3. The effect of age on nutrient intake was not significant. The daily intakes of non-soluble fiber, manganese, iron and copper by patients aged below 50 y were significantly higher than older patients.4. Regarding the relationship between BMI and nutrient intake. The daily intakes of fat, vitamin C, vitamin E, calcium, potassium and magnesium were the lowest by lean patients while the daily intake of non-soluble fiber was the highest.5. In terms of educational background, the daily intakes of energy, carbohydrate, non-soluble fiber, vitamin E, copper and manganese by patients with advanced educational background were higher than patients with primary educational background.6. In terms of income, the daily intakes of energy, protein, carbohydrate, non-soluble fiber, thiamin, riboflavin, niacin, vitamin C, vitamin E, potassium, magnesium, zinc, copper and manganese by patients earning 2000 yuan per month were the lowest.7. When nutrient intake by patients was compared with RNIs or AIs, energy intake was lower than the reference value of RNIs. Protein intake was similar with RNIs. Calcium intake was extremely insufficient while phosphorus intake was extremely higher than the reference value of 700 mg/d. Iron intake by males was higher while zinc intake by males below 50 y was insufficient. Selenium intake by patients from all age groups was below RNIs, particularly by the patients from 60~70 y group and 70~ 80 y group. Copper intake meets the reference value by patients except those from 70~ 80 y group. Intakes of manganese, vitamin A, vitamin E, vitamin C and niacin were higher than reference values. Intakes of thiamin and riboflavin were below the reference values by all age group except 60~ 70 y group.8. As for the biological parameters of T2 D patients, FPG was 8.3 mmol/L in males while 8.1 mmol/L in females. Hb A1 c was 8.3 % in both genders. HDL-C lever of males was lower than criterion. Antioxidative parameters of 96 T2 D patients were measured. Levels of FRAP and SOD were below the normal range while MDA level was higher than the reference value.Part 2 Effects and mechanism of propolis on energy metabolism and oxidative stress of patients with type 2 diabetes1. There were no significant differences between two groups in terms of intakes of energy, protein, fat and carbohydrate. Intakes of nutrients including vitamin A, vitamin B, vitamin E, potassium, sodium, iron, zinc and selenium were not significantly different between two groups except that intakes of vitamin C and calcium in propolis group was lower than control group(P< 0.05). WHR was more than 0.9 and BMI was more than 24 kg/m2 in both groups. Weight, BMI and WHR were not significantly different between two groups.2. Before intervention, there were no differences between two groups in terms of levels of FPG, Hb1 Ac, insulin, FRAP, SOD, GSH, GSH-Px, MDA, LDH, AR.3. After intervention, levels of FPG, Hb1 Ac, insulin, AR and adiponecin in propolis group were not significantly different from control group. Levels of GSH and total polyphenols were higher in propolis group than control group(P< 0.05) while the level of carbonyls was lower than control group(P< 0.05). Levels of FRAP, SOD, GSH-Px, MDA and ox-LDL were not significantly different between two groups. Compared with control group, levels of IL-1β and IL-6 were higher while TNF-α level was lower in propolis group(P< 0.05).Conclusion1. A food frequency questionnaire(FFQ) suitable for citizens of Tianjin was designed for this cross-sectional study. They were asked to retrospect their food intake during the past month. The questionnaire was designed considering their eating habits and lifestyle in order to get the accurate data easily.2. Most T2 D patients in Tianjin were middle-aged and elder with high BMI, indicating that it is important to prevent T2 D by dietary and weight control. Compared with RNIs or AIs, intakes of energy, protein and certain nutrients were lower by T2 D patients. Therefore, it is important to get their attention to dietary control.3. The investigation illustrated that fasting plasma glucose(FPG) and Hb A1 c of T2 D patients were unsatisfactory. Levels of antioxidants of patients were lower while levels of lipid peroxides were higher than normal. It indicated that there was oxidative stress in their body. Therefore, it is crucial to find a substance that slow the progression of T2 D as dietary control alone seems to be failed to control blood glucose level.4. After intervention, levels of FPG, Hb1 Ac, insulin, AR and adiponecin in propolis group were not significantly different from control group, indicating that there were no effects of propolis on glucose metabolism of T2 D patients.5. Propolis could improve the level of GSH of T2 D patients, indicating that propolis could increase the amount of antioxidants. Propolis could increase the amount of polyphenols in plasma, indicating that polypheols in propolis are bioaccessible and could improve antioxidant function of T2 D patients.6. After intervention, level of TNF-α and activity of LDH decreased while levels of IL-1β and IL-6 increased. It illustrated that propolis could alleviate inflammation and improve energy metabolism.