Almond consumption improved glycemic control and lipid profiles in patients with type 2 diabetes mellitus Sing-Chung Lia,1, Yen-Hua Liua,1, Jen-Fang Liua, Wen-Hsin Changa, Chiao-Ming Chenb, C.-Y. Oliver Chenc,��� a School of Nutrition and Health Science, Taipei Medical University, Taipei City, 110, Taiwan b Department of Food Science, Nutrition and Nutraceutical Biotechnology, Shih Chien University, Taipei City, 110, Taiwan c Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA Received 13 January 2010 accepted 12 April 2010 Abstract Almond consumption is associated with ameliorations in obesity, hyperlipidemia, hypertension, and hyperglycemia. The hypothesis of this 12-week randomized crossover clinical trial was that almond consumption would improve glycemic control and decrease the risk for cardiovascular disease in 20 Chinese patients with type 2 diabetes mellitus (T2DM) (9 male, 11 female 58 years old body mass index, 26 kg/m2) with mild hyperlipidemia. After a 2-week run-in period, patients were assigned to either a control National Cholesterol Education Program step II diet (control diet) or an almond diet for 4 weeks, with a 2-week washout period between alternative diets. Almonds were added to the control diet to replace 20% of total daily calorie intake. Addition of approximately 60 g almonds per day increased dietary intakes of fiber, magnesium, polyunsaturated fatty acid, monounsaturated fatty acid, and vitamin E. Body fat determined with bioelectrical impedance analysis was significantly lower in patients consuming almonds (almonds vs control: 29.6% vs 30.4%). The almond diet enhanced plasma ��-tocopherol level by a median 26.8% (95% confidence intervals, 15.1-36.6) compared with control diet. Furthermore, almond intake decreased total cholesterol, low-density lipoprotein cholesterol, and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol by 6.0% (1.6-9.4), 11.6% (2.8-19.1), and 9.7% (0.3-20.9), respectively. Plasma apolipoprotein (apo) B levels, apo B/apo A-1 ratio, and nonesterified fatty acid also decreased significantly by 15.6% (5.1-25.4), 17.4% (2.8-19.9), and 5.5% (3.0-14.4), respectively. Compared with subjects in the control diet, those in the almond diet had 4.1% (0.9-12.5), 0.8% (0.4-6.3), and 9.2% (4.4-13.2) lower levels of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance index, respectively. Our results suggested that incorporation of almonds into a healthy diet has beneficial effects on adiposity, glycemic control, and the lipid profile, thereby potentially decreasing the risk for cardiovascular disease in patients with type 2 diabetes mellitus. �� 2011 Elsevier Inc. All rights reserved. 1. Introduction More than 20 million people have type 2 diabetes mellitus (T2DM) in the United States and 135 million worldwide, and the number unfortunately keeps growing mainly because of a prevalence of overweight and obese populations. The burden of health issue related to the DM patients is beyond that resulting from diabetes-related complications. Because cardiovascular risk factors cluster in T2DM, these patients have greater risk for cardiovascular disease (CVD) than nondiabetic equivalents even when blood glucose levels are under control [1]. The main components of T2DM include hyperglycemia, oxidative stress, chronic mild inflammation, and dyslipidemia and they all are associated with increased risk of CVD. The standard treatment for T2DM patients is to control blood glucose and lipid profile in the recommended ranges. Health-promoting lifestyle and dietary practices may also help better manage diabetes-related complications, particularly CVD because it accounts for greater than 70% morbidity and mortality [2]. Tree nuts have become a healthy food, with support from a growing body of epidemiologic evidence showing a strong association of nut consumption to lower risk of CVD and Available online at www.sciencedirect.com Metabolism Clinical and Experimental 60 (2011) 474���479 www.metabolismjournal.com Institutional approval: The study protocol was approved by the Institutional Review Board of the Taipei Medical University, and written consent was obtained from each participant prior to participation in the study. ��� Corresponding author. E-mail address: oliver.chen@tufts.edu (C.-Y.O. Chen). 1 This authors contributed equally to this work. 0026-0495/$ ��� see front matter �� 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2010.04.009

diabetes [3-5]. This benefit may underlie the nut nutrients that comply with the recommended dietary guidelines for Americans and fit very well into a heart-healthy diet. Particularly, nuts are rich sources of unsaturated fats, fiber, minerals, and proteins [6]. Furthermore, epidemiologic and clinical evidence has shown that their consumptions were associated with improved hyperlipidemia and insulin sensitivity, decreased inflammation and oxidative stress, and reduced/maintained body weight [7]. The American Diabetes Association also recommends inclusion of nuts into the diet of diabetes to treat or manage CVD risk [8]. Almonds are the most consumed tree nut, with per capita nut consumption at 1 lb/y in the United States [9]. Almonds may be cardioprotective because they are excellent sources of monounsaturated fats, ��-tocopherol, dietary fiber, copper, magnesium, arginine, plant sterols, and polyphenols [6,10]. Most almond studies in the literature have illustrated the hypolipidemic effect of almonds in healthy subjects or hypercholesterolemic patients. Regarding glycemic control, Jenkins et al [11] found that almonds lowered postprandial glucose excursion in healthy individuals. However, Lovejoy et al [12] had found that almonds incorporated into a low- or high-fat diet did not affect glycemia and lipid profiles of American T2DM patients. In this controlled feeding study, we aim to investigate the extent by which incorporation of almonds into the National Cholesterol Education Program (NCEP) [13] step II diet improves insulin sensitivity and lipid profile in Chinese T2DM patients. 2. Materials and methods 2.1. Subjects Thirty Chinese T2DM patients previously diagnosed by a physician were recruited from the Endocrine Clinic of the Taipei Medical University Hospital, Taiwan. Among them, 8 patients were not qualified for the study because they did not meet all of the following eligibility criteria. The eligibility criteria included (1) serum cholesterol greater than 200 mg/dL or triglycerol greater than 150 mg/dL, free of dietary restrictions/food allergies (2) not receiving insulin therapy (3) not using medications or supplementations known to alter lipid metabolism (4) stable blood lipid and sugar levels within 3 months before study (5) no clinical history of cardiovascular, hepatic, gastrointestinal, or renal disease (6) no alcoholism and (7) no recent history of smoking. All women were postmenopausal, and all subjects were taking oral hypoglycemic agents. All participants were asked to stay with the same medications and refrain from nuts and supplements. Three-day dietary record, including 2 weekdays and 1 weekend day, was collected weekly from the subjects to monitor dietary compliance and assess nutrient intakes. The study protocol was approved by the Institutional Review Board of the Taipei Medical University, and written consent was obtained from each participant before participation in the study. 2.2. Study design In a 12-week randomized crossover trial with a 2-week washout between alternative diets, subjects were assigned to receive control or almond diet for 4 weeks after a 2- week run-in period (Fig. 1). To diminish the impact of background diet on study outcomes, patients consumed meals prepared by the metabolic kitchen of Taipei Medical University Hospital during dietary interventions. During run-in and washout periods, the subjects consumed their habitual diets without nuts and a daily diet diary was used to monitor the compliance. A registered dietitian instructed all participants on how to select appropriate foods during run-in and washout periods and prepare dietary records. Four overnight-fast blood samples and anthropometric data were collected from each participant before and after each dietary treatment. 2.3. Diets Meals for each patient were prepared to meet daily caloric requirement to maintain body weight by the metabolic kitchen of the Taipei Medical University Hospital. Caloric adjustments were made as needed to maintain body weight within 2 kg of each person's initial value. Based on the NCEP step II dietary guideline [13], the control diet was designed to provide daily calories from carbohydrate, protein, and fat at 56%, 17%, and 27%, respectively. Furthermore, calories from saturated and polyunsaturated fat were less than 7% and 10%, respectively and cholesterol content was less than 200 mg. The almond diet was prepared by incorporating roasted, unsalted whole almonds with skins into meals to replace 20% calories of the control diet. Depending on the menus, almonds were either incorporated into entrees and deserts or consumed as snack. On average, a patient consumed 56 g of almonds a day. Almonds were sweet almonds containing small amounts of cyanogenic compounds [11]. They were generously provided by the Almond Board of California. A 5-day menu rotation was used to make food more appealing and palatable to the participants throughout the study. The participants were provided with all foods needed during the dietary interven- Fig. 1. Study design. 475 S.-C. Li et al. / Metabolism Clinical and Experimental 60 (2011) 474���479