The relation of low glycaemic index fruit consumption to glycaemic control and risk factors for coronary heart disease in type 2 diabetes

Details of the study protocol have been reported previously [15]. Recruitment took place from May 2004 to December 2006, with the last follow-up visit at the end of May 2007. Of those recruited, 210 were found to be eligible and were randomised. Eligible participants were men or postmenopausal women with type 2 diabetes who were taking oral agents to control their diabetes, with medications stable for the previous 3 months and who had HbA_1c values at screening between 6.5% and 8.0% (Table 1). None had clinically significant cardiovascular, renal or liver disease (alanine transaminase > three times the upper limit of normal) and none was undergoing treatment for cancer. Individuals were accepted after surgery or myocardial infarction providing an event-free 6 month period had elapsed prior to the study. This study is a secondary analysis, but differs from the original study [15] in that it focuses on the 152 participants who completed the study and also provided 7 day food records, which were used to determine fruit intake.

The study was approved by the research ethics board of St Michael’s Hospital and the University of Toronto, and written consent was obtained from all participants.

In this secondary analysis of completer data from a previously published study [15], participants were randomised to one of two parallel 6 month treatments: a low GI diet or a high cereal fibre diet. During the study, equally strong emphasis was placed by dietitians on the potential value of both treatments.

Participants were seen at the Clinical Nutrition and Risk Factor Modification Center of St Michael’s Hospital, a University of Toronto Teaching Hospital, at baseline, weeks 2 and 4, and thereafter at monthly intervals until the end of the 6 month period. During the first month, participants received instructions on the diet to which they were allocated. At all centre visits, participants were weighed in indoor clothing without shoes and a fasting blood sample was taken. Blood pressure was measured seated on three occasions at 1 min intervals using an Omron automatic sphygmomanometer (OMRON Healthcare, Burlington, ON, Canada) and the mean of the three measurements was taken. In addition, participants brought with them their 7 day food records covering the week prior to the visit and these were discussed with the dietitians.

During the study, participants were asked to maintain their exercise pattern and keep their glucose-lowering agents constant throughout the study.

General dietary advice conformed to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the ADA guidelines [16] to reduce saturated fat and cholesterol intakes [17]. Of all the participants, 84.9% were overweight (BMI ≥ 25 kg/m²) and 50.7% were obese (BMI ≥ 30 kg/m²) and wished to lose weight. They were informed that this was not a weight loss study but appropriate advice was given on portion size and fat intake to help them meet their body weight objectives. Participants were also provided with a checklist with either low GI or high cereal fibre food options as approximately 15 g carbohydrate servings. The number of carbohydrate servings prescribed covered 42–43% of total dietary energy. Three servings of fruit and five servings of vegetables were encouraged on both treatments. On the low GI treatment, the carbohydrate intakes emphasised were low GI breads, breakfast cereals, parboiled rice, pasta, beans, barley, bulgar and low GI fruit. Temperate climate fruit, which are generally low GI, were the focus and included apples, pears, citrus fruit (oranges, tangerines and grapefruit), berries (strawberries, raspberries, cranberries, blackberries and blueberries) and the Prunus family (nectarines, peaches and plums). On the cereal fibre treatment, the focus was on wholewheat breads, breakfast cereals and tropical fruit with glycaemic indices that were closer to that of the average diet, such as bananas, mangoes, guavas, grapes, raisins, watermelon and cantaloupe. Low GI or temperate climate fruit had GI values of <70 GI units (bread scale), with the exception of blueberries, with a value of 76 GI units, based on recent values for individuals without diabetes [18]. Higher GI fruit, predominantly tropical fruit, had values >70 GI units [18]. Participants were also advised against eating fruit recommended on the alternative treatment. Checklists were completed by participants on a daily basis throughout the study and 7 day diet records were completed prior to each visit. Adherence was assessed from the 7 day diet records. The overall aim was to achieve a 10–20% reduction in GI on the low GI diet while keeping dietary fibre similar between treatments.

Blood glucose was measured in the hospital routine analytical laboratory by a glucose oxidase method using a Random Access Analyzer and reagents (SYNCHRON LX Systems, Beckman Coulter, Brea, CA, USA) (CV 1.9%). HbA_1c was analysed by a designated HPLC method (Tosoh G7 Automated HPLC Analyzer, Grove City, OH, USA) (CV 1.7%). Serum was analysed for total cholesterol, triacylglycerol (TG) and HDL-cholesterol, also using a Random Access Analyzer (CV 1.5–2.4%). Diets were assessed for available carbohydrate (total carbohydrate–fibre) using a computer program based on US Department of Agriculture data [19].

The primary outcome was HbA_1c, with glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, TG, blood pressure, body weight and CHD risk as secondary measures. Analyses were undertaken on individuals who completed the study and also provided diet records at the start of and during the study (n = 152).

Baseline data are expressed as means ± SDs. All other data are expressed as means (95% CI). All analyses were carried out using SAS software, version 9.2 [20].

Pearson correlations as well as partial correlations controlling for body weight change and change in fibre intake were undertaken to determine the relation of low GI fruit to measures of glycaemic control and CHD risk. The data from the two treatments were pooled and both the absolute differences in servings of fruit, and the carbohydrate from fruit expressed as a percentage of the total carbohydrate, were related to the percentage changes from baseline in the outcome measures. Overall 10 year CHD risk was calculated according to the Framingham cardiovascular risk equation [21]. In our current analyses, only raw and frozen fruit were included. We excluded processed fruit products such as juices, canned fruit and jams as unmodified fruit was the focus of our assessment. Two-sample Student’s t test was used to assess differences between treatments at baseline and between changes across treatments. Binomial tests of equality were used to assess differences at baseline for categorical variables.

Participants were also divided into four equal groups based on the magnitude of the change they made in low GI fruit intake, expressed as a percentage of daily available carbohydrate from fruit \( \left[ {\left( {{\hbox{available carbohydrate from fruit }} \div {\hbox{ total available carbohydrate in the diet}}} \right) \times {1}00} \right]. \) The significance of differences between those in the upper quartile of change in low GI fruit intake vs those in the lowest quartile was assessed using an ANOVA model (Proc GLM in SAS version 9.2) [20], with percentage change in measurements as the response variable.

Finally, to assess the contribution of low GI fruit to the absolute change in HbA_1c, as the primary outcome in the context of the other major low GI food components, a regression analysis was undertaken in SAS using an ANOVA model. In this analysis, the assessment of each dietary component was carried out in a model adjusted for change in fibre (g/kJ or kcal) and total fruit intake (% of available carbohydrate). The eight individual low GI dietary components were fruit, bread, breakfast cereals, pasta, beans, parboiled rice, barley and bulgar, each expressed as a percentage of total carbohydrate.