The Effect of Whole Almonds on Biomarkers of Cardiovascular Disease in Chinese Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of the study is to examine whether almond consumption for 3 month will help Chinese patients with type 2 diabetes control blood glucose and decrease risk factors of cardiovascular disease.

Detailed Description
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Our previous study demonstrated almonds ( 60 g/d) improved lipid profile, glucoregulation, inflammation, and oxidative stress in 20 Chinese patients with type 2 diabetes mellitus (T2DM). To follow-up and expand this work with a more robust trial, the investigators propose a larger (n = 40), longer-term (90-d) investigation of the effect of almonds ( 60 g/d) on adipokine regulation, endothelial function, glucoregulation, inflammation, lipid profile, and oxidative stress in Chinese patients with T2DM as compared to a placebo control. The investigators will conduct a 7-mo randomized, cross-over, placebo controlled clinical trial in which all meals will be provided to all subjects (n = 40). During the first 2 weeks (run-in period), all subjects will receive a control diet resembling a typical Taiwan diet, prepared based on the NCEP Step 2 guidelines. During the following 3 mo (Phase I), subjects will be randomized to receive either the control diet or the control diet with whole almonds ( 60g/d) incorporated to replace 20% calories. After a 2-wk washout period during which all subjects will once again receive the control diet, subjects will receive the opposite diet to the one assigned during the Phase I for the other 3 months (Phase II). The caloric content of each diet will be adjusted to each subjects' energy needs to prevent any change in body weight. The following biomarkers will be determined at the baseline and end of each dietary intervention: Glucoregulation: fasted serum HbA1c, glucose and insulin, postprandial serum glucose and insulin, and urinary C-peptide; Endothelial Function: brachial artery FMD and serum nitric oxide, e-selectin, endothelial-1 (ET-1), and intracellular adhesion molecule-1 (ICAM-1); Adipokine Regulation: serum adiponectin, leptin, and resistin; Inflammation: serum high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-10, retinol binding protein-4 (RBP-4), and tumor necrosis factor (TNF)-α; Oxidative Stress: urinary isoprostanes (adjusted for creatinine) and serum protein carbonyls and oxidized LDL; and Lipid Profile: serum cholesterol, triglycerides, and apolipoproteins A1 and B.

Official Title
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The Effect of Whole Almonds on Glucoregulation, Endothelial Function, Inflammation, Lipid Profile, and Oxidative Stress in Chinese Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Other: Almond diet first, then NCEP Diet
* Other: NCEP diet first, then Almond diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 40-70 years, with BMI = 24-35 kg/m2, HbA1c 6.5-9 %, and regular use of oral hypoglycemic agents. Exclusion Criteria: Use of insulin to control blood glucose Regular use of oral steroids Regular use of anti-inflammatory agents (prescribed [Rx] or over-the-counter [OTC]) Gain or loss of larger than 5% of body weight in the last 6 months CVD: coronary artery disease, left ventricular hypertrophy evidenced by echocardiogram, congestive heart failure, cerebrovascular disease, stroke, peripheral vascular disease, dysautonomia Gastrointestinal: diseases, conditions, or medications influencing gastrointestinal absorption including active peptic ulcer disease, inflammatory bowel disease, treatment with acid-lowering drugs Renal: chronic kidney disease due to any condition, renovascular disease, history of nephrolithiasis, diabetic nephropathy, serum creatinine > 1.5 mg/dL Endocrine: disease, untreated thyroid disease, adrenal disease, pheochromocytoma, parathyroid disease, hyperuricemia Rheumatologic: gout, inflammatory arthritis Active treatment for cancer of any type (except basal cell carcinoma) 1 year Systolic blood pressure larger than 150 mmHg, and diastolic blood pressure larger than 95 mmHg. Any history of or known allergies to nuts of any kind Frequent nut consumption, defined as ≥ 3 oz/wk; however, subjects who are willing to refrain from eating all nuts and nut products for 6 wk prior to their initial visit (Visit 1) may be considered eligible Regular use of any dietary supplements containing vitamins, minerals, herbal or other plant-based preparations, fish oil supplements (including cod liver oil) or homeopathic remedies; however, subjects who are willing to refrain from the use of these supplements for 1 mo prior to their initial visit (Visit 1) and throughout the entire study may be considered eligible Usual daily ethanol intake of larger or equal to 2 drinks (24 oz beer, 8 oz wine, 2 oz hard liquor) Illicit drug use Specific laboratory blood or urine analysis parameters of: creatinine larger than 1.5 mg/dL, ALT and AST larger than 1.5 nmol/L, and urinalysis - hematuria and proteinuria

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Almond diet first, then NCEP Diet<br>In a 28-wk randomized, cross-over, controlled feeding trial with a 2 week washout between alternative diets, subjects were assigned to receive NCEP or almond diet for 12 weeks after a 2-weeks run-in period | Other: Almond diet first, then NCEP Diet<br>* whole almonds will be incorporated into a control diet which is a NCEP step 2 diet. Whole almonds will replace 20% daily calorie intake. Subjects were assigned to receive almond diet for 12 weeks after a 2-weeks run-in period. After washout 2 weeks, change diet to NCEP Diet for 12 weeks<br>|
| Experimental: NCEP diet first, then Almond diet<br>In a 28-wk randomized, cross-over, controlled feeding trial with a 2 week washout between alternative diets, subjects were assigned to receive NCEP or almond diet for 12 weeks after a 2-weeks run-in period | Other: NCEP diet first, then Almond diet<br>* NCEP diet first, then Almond diet. Subjects were assigned to receive NCEP diet for 12 weeks after a 2-weeks run-in period. After washout 2 weeks, change diet to almond diet for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Major Nutrients of NCEP Step 2 Diet and Almond Diets |  | the entire study, up to 3 months | 
| Plasma Lipid Profiles at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| The Calories of NCEP Step 2 Diet and Almond Diets |  | the entire study, up to 3 months | 
| Lipid Composition of NCEP Step 2 Diet and Almond Diets |  | the entire study, up to 3 months | 
| Body Weight at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Body Fat Percentage at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Blood Pressure at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Fasting Glucose at the Baseline and the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Area Under Curve of Plasma Glucose After Eating Standard Breakfast at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Fasting Insulin at the Baseline and the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Area Under Curve of Plasma Insulin After Eating Standard Breakfast at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma HbA1c Level at the Baseline and the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| HOMA at the Baseline and the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Apolipoprotein Level at the Baseline and the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Nitric Oxide Level at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Endothelial Function at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Protein Carbonyl Level at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Oxide LDL Level at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Urine Isoproterenol Level at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 
| Plasma Vitamin E Level at the Baseline and at the End of 3-month Dietary Intervention |  | at the baseline and at the end of 3-month dietary intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyperglycemia, hyperinsulinemia