Effects of Dried Whole Fruits on Metabolism in Diabetes

Subject recruitment: Untreated prediabetes or new type 2 diabetic (T2D) patients (males and females, 18-74 years of age) and willing to sign an informed consent will be recruited from community clinics in Winnipeg, Endocrine or Hepatologic Clinics in University of Manitoba and Rossmere Medical Centre in Winnipeg by posters. Exclusion criteria include: 1) candidates have a history of myocardial infarction, stroke or chronic kidney disease; 2) participants treated with hypoglycemic, anti-hypertensives, lipid lowering medications or antibiotics within a month. Candidates will be invited to read and voluntarily sign an informed consent approved by Research Ethics Board in University of Manitoba. Recruitment goal: n = 92 (80 + 15% expected drop-off).

Randomization: Eligible participant will be enrolled and randomization into two groups through a web randomization tool. Randomized ID will be obtained for each participant used in files or labels on packages of dried fruits.

Dietary supplements: Freeze dried Saskatoon berry (SB) have been obtained from Prairie Berries Inc. The berries were freshly frozen and no supplementation was added to the dried berry. The product has been processed by certified facilities and the batch of dried berry has passed pathogen analysis. Control dietary supplement will be dried apple slice bulk without supplementation (Vancouver Freeze Dry, Langley, BC). Two types of dietary supplements will be weighed and packed: 1) 40 g of dried whole SB/bag; 2) dried apple slice bulk in a weight containing carbohydrate equivalent to 40 g of SB/bag). Non-transparent bags labeled only with randomization ID will be used for the package of the fruits.

Duration of the dietary regimen: 12 weeks.

Scheduled visits:

Visit 1: Consent and enrollment. A questionnaire for domestic questionnaire including dietary intake and physical activity will be filled. Measurements of body weight, height and blood pressure will be taken during the visit.

Visit 2 (<1 week from the visit 1 and before the start of berry administration): Blood withdrawal at Health Sciences Center (HSC) in Winnipeg after an overnight fasting. Fasting plasma glucose, insulin, HbA1C, lipid profile, liver enzymes (alanine transaminase or ALT, aspartate transaminase or AST), apoB, apoA-I, and creatinine will be analyzed in Clinical Chemistry in HSC. An extra 3 ml of blood withdraw in serum tube. The serum will be temporarily stored in Clinical Chemistry for measuring insulin, GLP-1 and high-sensitive C-reactive protein (hs-CRP) by Investigator's group.

Visit 3 (at 6 weeks after the start of administration of Saskatoon berry): Participants will be asked to provide feedback on general well-being and the intake of Saskatoon berry. Body weight, blood pressure and heart rate will be measured and recorded.

Visit 4 (at 12 weeks after the start of the dietary regimen): Participants will be asked to collect stool sample with the collection kit within 1 week before the visit and bring it to the visit. They will also be asked to have an overnight fasting the night before visit. Blood samples will be collected for biochemical analyses as descried in Visit 2. Same amount blood will be collected for serum temporarily stored for the analysis of GLP-1 and hs-CRP. During the visit, body weight, blood pressure and heart rate of participants will be taken. Questionnaires on participants' dietary intake, physical activity and feedback to the study will be completed. Homeostatic model assessment-insulin resistance or homeostatic model assessment for insulin resistance (HOMA-IR) will be calculated based on fasting plasma glucose and insulin. Stool samples will be aliquoted and stored under -80°C before shipment to analysis in Integrate Microbiome Resource at Dalhousie University.

Data collection and analysis: Biochemical, physical exam, questionnaires, surveys, results from gut microbiota and SCFAs will be collected and inputted to password protected computers of PI and Project Coordinator with only ID but not names or other identifiable information. Data will be analyzed using standards statistical software and tools.

Expected outcomes Primary outcome: Fasting plasma glucose at the end of 12 weeks of SB intake compared to baseline.

Secondary outcomes: HBA1c, fasting serum total cholesterol, LDL-cholesterol, triglyceride, insulin resistance, GLP-1, AST, ALT, CAP (fibroscan), creatinine, hs-CRP, SBP and DBP at the end of 12 weeks of SB intake versus baseline.

Inclusion criteria

• Untreated pre-diabetes with or without fatty liver disease
• Untreated type 2 diabetes with or without fatty liver disease
• Males and females (18-74 years)
• Signed informed consent

Exclusion criteria

• Treated with hypoglycemic, hypolipidemic, anti-hypertensive or antibiotics within 1 month
• Acute myocardial infarction, stroke, heart failure, chronic kidney disease, cirrhosis, metastatic cancers
• Currently pregnancy or nursing
• Allergy to fruits