Clinical trial NCT00410722: Effect of Nuts vs. a Wheat Bran Muffin in Type 2 Diabetes
Official title: Effect of Nuts on Glycemic Control and Cardiovascular Disease Risk in Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Type 2 Diabetes
Cardiovascular Disease
Diet Therapy
Keywords: Nutrition
Type 2 Diabetes
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2006-12-13
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Markers of glycemic control: Fasting serum fructosamine
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, 12
measure: Fasting serum HbA1c
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Fasting glucose
timeFrame: From prestudy and week 0, to end of treatment and weeks 8, 10, and 12
measure: Fasting insulin
timeFrame: From prestudy and week 0, to end of treatment and weeks 8, 10, and 12
Secondary outcomes:
measure: 24h urinary C-peptide excretion
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Branched chain amino acids
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Serum triglyceride
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Very Low-Density Lipoprotein (VLDL) triglyceride
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: VLDL-C
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: LDL:HDL-C
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Apolipoprotein B:A1
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Lipoprotein(a)
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: oxidized LDL
timeFrame: From beginning of study, week 0, to end of treatment week 12
measure: markers of oxidative stress
timeFrame: From beginning of study, week 0, to end of treatment week 12
measure: C-reactive protein
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: markers of inflammation
timeFrame: From prestudy and week 0, to end of treatment weeks 8, 10, and 12
measure: Cancer cell proliferation
timeFrame: From beginning of study, week 0, to end of treatment week 12
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
Study officials:
affiliation: University of Toronto, St. Michael's Hospital
name: David JA Jenkins, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toronto, St. Michael's Hospital
name: Cyril WC Kendall, PhD
role: STUDY_CHAIR
References:
citation: Jenkins DJA, Kendall CWC, Lamarche B, Banach MS, Srichaikul K, Vidgen E, Mitchell S, Parker T, Nishi S, Bashyam B, de Souza RJ, Ireland C, Pichika SC, Beyene J, Sievenpiper JL, Josse RG. Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial. Diabetologia. 2018 Aug;61(8):1734-1747. doi: 10.1007/s00125-018-4628-9. Epub 2018 May 23.
citation: Nishi SK, Kendall CW, Bazinet RP, Bashyam B, Ireland CA, Augustin LS, Blanco Mejia S, Sievenpiper JL, Jenkins DJ. Nut consumption, serum fatty acid profile and estimated coronary heart disease risk in type 2 diabetes. Nutr Metab Cardiovasc Dis. 2014 Aug;24(8):845-52. doi: 10.1016/j.numecd.2014.04.001. Epub 2014 May 13.
citation: Jenkins DJ, Kendall CW, Banach MS, Srichaikul K, Vidgen E, Mitchell S, Parker T, Nishi S, Bashyam B, de Souza R, Ireland C, Josse RG. Nuts as a replacement for carbohydrates in the diabetic diet. Diabetes Care. 2011 Aug;34(8):1706-11. doi: 10.2337/dc11-0338. Epub 2011 Jun 29.