Effect of Nuts vs. a Wheat Bran Muffin in Type 2 Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
David Jenkins, University of Toronto
ClinicalTrials.gov Identifier:
NCT00410722
First received: December 12, 2006
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

To determine if tree nuts (Almonds, Hazelnuts, Pistachios, Peanuts, Macadamia nuts, Pecans, Walnuts and Cashews) improve glycemic control in type 2 diabetes, as assessed by HbA1c and serum fructosamine, and to assess whether these outcomes relate to improvements in cardiovascular health (i.e. plasma lipids and measures of oxidative stress, inflammatory biomarkers and nitric oxide generation). The investigators have found that nuts tend to reduce the glycemic index of bread and have little effect of raising blood glucose on their own. Therefore the investigators believe that they would be ideal foods to displace high glycemic foods from the diet and lower the dietary glycemic load. This will result in improved blood glucose control in type 2 diabetes, with additional benefits on coronary heart disease risk factors due to other effects of nuts.


Condition Intervention Phase
Type 2 Diabetes
Cardiovascular Disease
Diet Therapy
Dietary Supplement: Whole wheat and bran muffin
Dietary Supplement: Mixed tree nuts
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Nuts on Glycemic Control and Cardiovascular Disease Risk in Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Toronto:

Primary Outcome Measures:
  • Markers of glycemic control: Fasting serum fructosamine [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, 12 ] [ Designated as safety issue: Yes ]
  • Fasting serum HbA1c [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Fasting glucose [ Time Frame: From prestudy and week 0, to end of treatment and weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Fasting insulin [ Time Frame: From prestudy and week 0, to end of treatment and weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 24h urinary C-peptide excretion [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Branched chain amino acids [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Serum triglyceride [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Very Low-Density Lipoprotein (VLDL) triglyceride [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • VLDL-C [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • LDL:HDL-C [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Apolipoprotein B:A1 [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Lipoprotein(a) [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • oxidized LDL [ Time Frame: From beginning of study, week 0, to end of treatment week 12 ] [ Designated as safety issue: No ]
  • markers of oxidative stress [ Time Frame: From beginning of study, week 0, to end of treatment week 12 ] [ Designated as safety issue: No ]
  • C-reactive protein [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • markers of inflammation [ Time Frame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12 ] [ Designated as safety issue: Yes ]
  • Cancer cell proliferation [ Time Frame: From beginning of study, week 0, to end of treatment week 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: December 2006
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Full-Dose Nut
Subjects will be given tree nuts (almonds, hazelnuts, pistachios, macadamia nuts, pecans, walnuts, and cashews) and peanuts (at a predetermined amount to consume based on their recommended energy intake), and advised to follow a diabetic diet.
Dietary Supplement: Mixed tree nuts
Experimental: Half-Dose Nut
Subjects will be given tree nuts (almonds, hazelnuts, pistachios, macadamia nuts, pecans, walnuts, and cashews) and peanuts as well as the control supplement (wheat bran muffin)(at a predetermined amount to consume based on their recommended energy intake), and advised to follow a diabetic diet.
Dietary Supplement: Whole wheat and bran muffin Dietary Supplement: Mixed tree nuts
Active Comparator: Control
Subjects will be given a control supplement (wheat bran muffin)(at a predetermined amount to consume based on their recommended energy intake), and advised to follow a diabetic diet.
Dietary Supplement: Whole wheat and bran muffin

Detailed Description:

The investigators wish to study the effect of nuts on glycemic control and to confirm their lipid lowering effects in type 2 diabetes. The consumption of nuts with their high unsaturated fat, vegetable protein (arginine) and fiber contents will decrease the glycemic load of the diet and improve glycemic control. The investigators anticipate that the favorable fatty acid profile of nuts along with the vegetable protein will improve the blood lipid profile in type 2 diabetes and thereby establish a cardiovascular risk reduction associated with nuts in this population.

Furthermore, flavonoids and vitamin E present in high concentrations in nuts, and known to have antioxidant activity may help to counter the elevated oxidative stress and inflammation experienced by diabetics. The investigators will therefore determine the effect of nut feeding on measures of oxidative stress (including oxidized low-density lipoprotein cholesterol (LDL-C), considered to be of direct relevance to coronary heart disease), inflammation (C-reactive protein, serum amyloid A and interleukin-6) and nitric oxide metabolism (blood nitric oxide and nitrotyrosine levels). These data would further add to interest in nuts in relation to cardiovascular disease risk reduction and diabetic complications.

Background Diet: A diet conforming to the American Diabetes Association (ADA) and National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines. Nuts, soy and dietary supplements (vitamins, minerals, herbal remedies) will be excluded in the background diet during all phases of the study.

Treatment diets:(1) Full-Dose Nut Diet: Raw nuts will be added as supplements to the subject's usual diet. Subjects with calorie needs of 2,400 kcal or greater, assessed by Lipid Research Clinic (LRC) tables, will receive the full-dose supplement (100 g/d of nuts, approximately 600 kcal). Subjects requiring between 1,600-2,400 kcal daily will receive 75% of the full-dose supplement (75 g/d of nuts, approximately 450 kcal). Subjects requiring less than 1,600 kcal daily will receive 50% of the full-dose supplement (50 g/d of nuts, approximately 300 kcal). (2) Half-Dose Nut Diet: Raw nuts will be added as supplements to the subject's usual diet. Subjects with calorie needs of 2,400 kcal or greater, assessed by LRC tables, will receive half of the full dose of the nut supplement (50 g/d of nuts, approximately 300 kcal) with the rest of the calories provided by the muffin (2 muffins are 300 kcal) for a total of 600 kcal. Subjects requiring between 1,600-2,400 kcal daily will receive 75% of the half-dose supplement (37.5 g/d of nuts and 1.5 muffins, approximately 450 kcal). Subjects requiring less than 1,600 kcal daily will receive 50% of the half-dose supplement (25 g/d of nuts and 1 muffin, approximately 300 kcal). (3): The full-dose control supplement will be four 150 kcal muffins. Control supplements will be matched with the energy content of the nut supplements, i.e. either 600 kcal/d (4 muffins); 450 kcal/d (3 muffins); 300 kcal/d (2 muffins). The macronutrient composition of the muffins will conform to an NCEP Step 2 diet with 25% total fat, <7% saturated fat by use of corn oil as the oil commonly used in healthy baked goods, with 18% protein (the average for our subject population) using added skim milk powder, and zero cholesterol. Muffins will be made with whole wheat flour.

Diet History: one-week weighed diet histories will be obtained prior to the start and at weeks 4, 8 and 12 of the study for assessment of macronutrients, dietary fiber and fatty acids.

Palatability/Satiety: for palatability and satiety, subjects will record their ratings using a 7-point bipolar semantic scale at monthly intervals during each study phase.

Anthropometry and Blood Pressure: height at recruitment and body weight, blood pressure, waist and hip circumference, and body composition will be taken immediately prior to and at each clinic visit (wk 0, 2, 4, 8, 10, 12) during the study.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and post menopausal women with type 2 diabetes treated with diet plus oral hypoglycemic agents (sulfonylureas (glyburide), biguanides (metformin), Thiazolidinediones (TZDs) and new secretagogues (Repaglinide)) at a stable dose for at least 3 months prior to starting the study;
  • HbA1c of 6.5 to 8.0% as a compromise between those whose levels are acceptable and the level which is currently considered unacceptable.
  • Diabetes diagnosed >6 months prior to randomization
  • Weight stable within 3% body weight >2 months.

Exclusion Criteria:

  • Use of acarbose
  • Use of Insulin
  • Known nut allergies
  • Clinically significant gastroparesis
  • Use of steroids
  • Presence of GI disease (celiac disease, ulcerative colitis, and Crohns)
  • Major cardiovascular event (stroke or myocardial infarction)
  • Major surgery < 6 months prior to randomization
  • Presence of major debilitating disorder such as clinically significant liver disease (not including non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) but including cirrhosis, infectious hepatitis (B and C), aspartate transaminase (AST) or alanine transaminase (ALT) > 130 IU/L)
  • Renal failure (high creatinine > 150 mmol/L)
  • Serum triglyceride > 6 mmol/L.
  • Patients currently undergoing treatment for cancer with the exception of non-melanoma skin cancer, but not high risk patients or those whose treatment has been successfully completed.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00410722

Locations
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5C 2T2
Sponsors and Collaborators
University of Toronto
Investigators
Principal Investigator: David JA Jenkins, MD, PhD University of Toronto, St. Michael's Hospital
Study Chair: Cyril WC Kendall, PhD University of Toronto, St. Michael's Hospital
  More Information

No publications provided by University of Toronto

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Jenkins, Principal Investigator, University of Toronto
ClinicalTrials.gov Identifier: NCT00410722     History of Changes
Other Study ID Numbers: REB 06-274
Study First Received: December 12, 2006
Last Updated: January 8, 2013
Health Authority: Canada: Health Canada

Keywords provided by University of Toronto:
Nutrition
Type 2 Diabetes

Additional relevant MeSH terms:
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 16, 2014