Provident Perspective Volume 4, Issue 3

Provident News

Provident welcomes our newest staff members.

·         Cassandra Abel, Lab Assistant

·         Esther Armstrong, RD, LD, Clinical Research Coordinator

·         Ana Diaz, Research Assistant

·         Jeanne Rosone, MLT (ASCP), Lab Manager

·         Kristen Taggart, Research Assistant

Congratulations and welcome to Provident!

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Announcements

·         The Addison, IL clinic officially opened for business in June. 

·         Congratulations to Arianne Orcutt for completing her Bachelor of Arts in Mathematics from DePaul University.

·         Congratulations also to Rose Hanbury, PhD.  Rose has resigned from Provident to pursue a new business opportunity.  She and her husband Bob are building a business selling custom nightlights and art kits directly to the consumer and to local area retailers.  Take a minute to visit their website at www.nightlightdesigns.com. Best wishes to Rose and Bob from the Provident team!

Recent and Upcoming Publications and Presentations

Publications

Maki KC, Carson ML, Miller MP, Kerr Anderson WH, Turowski M, Reeves MS, Kaden V, Dicklin MR. Hydroxymethylcellulose lowers cholesterol in statin-treated men and women with primary hypercholesterolemia. Eur J Clin Nutr (in press).

Toth PP, Maki KC. A commentary on the implications of the ENHANCE (ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression) trial: should ezetimibe move to the “back of the line” as a therapy for dyslipidemia? J Clin Lipidol, 2008 (in press).

Maki KC, Dose-response characteristics of high-viscosity hydroxypropylmethylcellulose in subjects at risk for the development of type 2 diabetes mellitus.  Diabetes Technology and Therapeutics (in press).

Voss AC, Maki KC, Carvey TW, Hustead DS, Alish C, Fix B, Mustad VA. Effect of two carbohydrate-modified tube-Feeding formulas on metabolic responses in patients with type 2 diabetes. Nutrition, 2008 (in press).

Maki KC, McKenney JM, Reeves MS, Lubin BC, Dicklin MR. Effects of adding prescription omega-3 fatty acid ethyl esters to simvastatin (20 mg/day) on lipids and lipoprotein particles in men and women with mixed dyslipidemia. American Journal of Cardiology. 2008;102:429-33.

Maki KC, Curry LL, Carakostas MC, Tarka SM, Reeves MS, Farmer MV, McKenney JM, Toth PD, Schwartz SL, Lubin BC, Dicklin MR, Boileau AC, Bisognano JD. The hemodynamic effects of rebaudioside A in healthy adults with normal and low-normal blood pressure. Food and Chemical Toxicology, 2008;46:S40-S46.

Maki KC, Curry LL, Reeves MS, Toth PD, McKenney JM, Farmer MV, Schwartz SL, Lubin BC, Boileau AC, Dicklin MR, Carakostas MC, Tarka SM. Chronic consumption of rebaudioside A, a steviol glycoside, in men and women with type 2 diabetes mellitus. Food and Chemical Toxicology, 2008:46:S47-S53.

Fan L, Hanbury R, Pandey SC, and Cohen RS. Dose and time effects of estrogen on expression of neuron-specific protein and cyclic AMP response element-binding protein and brain region volume in the medial amygdala of ovariectomized rats. Neuroendocrinology. 2008 (in press, epub ahead of publication).

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Abstracts/Presentations

The Obesity Society 2008 - Maki KC, Reeves MS, Farmer M, Yasunaga K, Matsuo N, Katsuragi Y, Komikado M, Tokimitusu I, Wilder DM, Jones F, Cartwright Y. Effects of daily consumption of a tea catechin containing beverage on exercise-induced changes in body composition and fat distribution in overweight and obese adults. Abstract, October 4^th, 2008. Poster #369-P.

The Obesity Society 2008 - Maki KC, Reeves MS, Carson ML, Miller MP, Turowski M, Rains, TM, Anderson K, Papanikolaou Y, Wilder DM. Dose-response characteristics of high-viscosity hydroxypropylmethylcellulose on postprandial glucose and insulin concentrations in subjects at risk for the development of type 2 diabetes mellitus. Abstract, October 4^th, 2008. Poster #368-P.

America Dietetic Association 2008 - Maki KC, Carson ML, Reeves MS, Herther DC, Anderson WHK, Miller MP, Dicklin MR. Effects of hydroxypropylmethylcellulose on fasting lipids in men and women with primary hypercholesterolemia receiving statin therapy. Tuesday (9:45 am – 11:15 am) October 28^th. Oral presentation (session 112).

The Diabetes Technology Society2008 - Alish CJ, Hustead DS, Maki KC, Reeves MS, Herther DC, Mustad. Continuous glucose monitoring demonstrates less glycemic variability with a diabetes-specific nutritional formula compared to a standard formula in patients with type 2 diabetes. The Diabetes Technology Society. November 13^th-15^th, 2008 (Poster).

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Books and Book Chapters

·         Toth PP, Maki KC. Practical Lipid Management: London: John Wiley & Sons, (in press). Expected release date December, 2008. Practical Lipid Management: Concepts and Controversies, is a text on the clinical management of dyslipidemias. As its title suggests, the book provides a straightforward and practical approach to the identification and treatment of abnormalities in lipid metabolism. The target audience consists of family physicians, internists, nurse practitioners, physician assistants, cardiologists, endocrinologists and allied health professionals involved in the care of patients with lipid disorders.

·         The book Therapeutic Lipidology edited by Drs. Michael Davidson, Peter Toth and Kevin Maki is available for purchase at Amazon.com

·         Maki KC. High-viscosity hydroxypropylmethylcellulose (HV-HPMC) a promising agent for metabolic risk factor management.  ACS Press, 2008 (in press).

·         Maki KC, Matsuo N, Dicklin MR. Clinical studies evaluating the benefits of diacylglycerol for managing excess adiposity.  In: Katsuragi Y, Yasukawa T, Matsuo N, Flickinger BD, Tokimitusu I, and Matlock MG. (eds) Chapter 10. Diacylglycerol Oil, AOCS Press, 2^nd ed. 2008.

·         Maki, KC and Dicklin M. How well do various lipids and lipoprotein measures predict cardiovascular disease morbidity and mortality. In: Toth PP, Sica D. (eds). Clinical Challenges in Lipid Disorders. Oxford: Clinical Publishing.  June, 2008.

·         Huth PJ, Rains TM, Yang Yifan, Philips SM. Current and emerging role of whey protein on muscle accretion.  In: Onwulata CI and Huth PJ. (eds) Chapter 13. Whey Processing, Functionality and Health Benefits. Wiley-Blackwell. 2008.

In the Literature

Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, et al.

Weight loss with a low-carbohydrate, Mediterranean , or low-fat diet.

N Engl J Med  2008;359:229-241.

Methods: This dietary intervention, randomized, controlled trial was designed to compare the safety and effectiveness of three types of popular weight loss diets: (1) a low-fat, restricted-calorie (based on the American Heart Association guidelines¹); (2) a moderate fat, restricted-calorie, Mediterranean (based on the recommendations of Willett and Skerrett²); or (3) a low-carbohydrate, non-calorie restricted diet (Atkins³).  Moderately obese men and women (n = 322, mean body mass index of 31 kg/m²) were assigned to one of these three diets and underwent periodic dietary counseling throughout the 2-year study. Both restricted-calorie diets were aimed at providing 1500 kcal/day for women and 1800 kcal/day for men. Subjects following the low-fat diet were instructed to target 30% calories from fat, 10% calories from saturated fat, and 300 mg cholesterol/day; while the Mediterranean diet had a goal of 35% of calories from fat (main sources were 30-45 g olive oil and 5-7 nuts per day).  The low-carbohydrate diet targeted 20 g carbohydrates per day (2-month induction phase) followed by 120 g/day (weight-loss maintenance phase).  Participants were weighed every month and fasting blood samples were collected at 6, 12, and 24 months for measurements of lipids, high-sensitivity C-reactive protein, adiponectin, leptin, glucose, insulin, glycated hemoglobin, and liver enzymes.        

Results:  Overall, subjects were 95.4% adherent to their diet following one year and 84.6% at two years (assessed by a validated food-frequency questionnaire).  Analysis of self-administered dietary questionnaires indicated that all groups had significant reductions from baseline daily energy intakes (p < 0.05), but there were no significant differences among the three diets. Dietary compositions were as expected; the low-fat diet group consumed lower amounts of saturated fat than the low-carbohydrate group, while the low-carbohydrate group consumed fewer grams of carbohydrates and higher amounts of protein, total fat, saturated fat, and total cholesterol than both other diet groups (p < 0.05 for all comparisons).  The Mediterranean-diet group consumed the highest ratio of monounsaturated to saturated fatty acids and had a higher dietary fiber intake than the low-carbohydrate group (p < 0.05 for all comparisons).  The low-carbohydrate group had the highest percentage of participants with detectable urinary ketones (8.3% vs. 4.8 and 2.8% in the low-fat and Mediterranean diet groups, respectively, p = 0.04). 

All groups lost weight, but the low-carbohydrate and Mediterranean diet groups lost more weight than the low-fat diet group (p < 0.001 for the interaction between diet group and time). The first six months was a weight loss phase, while the remainder of the study was a weight-maintenance phase. Mean weight losses for all 322 subjects at 24 months (including those who did not complete the study) were 2.9, 4.4, and 4.7 kg in the low-fat, Mediterranean , and low-carbohydrate diet groups, respectively.  Among the 272 participants who completed the full two years of the study, mean weight losses were 3.3, 4.6, and 5.5 kg, for the three diets, respectively (p = 0.03 for low-fat vs. low-carbohydrate groups at 24 months). Mean changes in body mass index were -1.0, -1.5, and -1.5 kg/m² for the low-fat, Mediterranean, and low-carbohydrate diet groups, respectively (p = 0.05 for comparison among groups). Waist circumference and blood pressure decreased significantly in all diet groups, but there were no significant differences among groups. 

There were no significant differences between the lipid responses of the low-fat and Mediterranean diet groups.  High-density lipoprotein cholesterol concentration increased in all diet groups, and to a significantly greater extent in the low-carbohydrate group compared to the low-fat group (8.4 vs. 6.3 mg/dL at 24 months, p = 0.01).  Triglyceride reductions were also significantly larger at 24 months with the low-carbohydrate diet compared to the low-fat diet (-23.7 vs. -2.8 mg/dL, p = 0.03), as was the relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol (-20% in the low-carbohydrate group vs. -12% in the low-fat group, p = 0.01).  The change in this ratio was intermediate for the Mediterranean diet group (17%).  There were no significant differences between or within diet groups in low-density lipoprotein cholesterol changes.

While both the Mediterranean diet and low-carbohydrate diet groups showed significant reductions from baseline in high-sensitivity-C-reactive protein (changes of -0.9 and -1.3 g/L, respectively, compared to -0.5 g/L in the low-fat diet group), there were no significant differences among the three groups.  High-molecular weight adiponectin increased significantly in all diet groups and circulating leptin decreased significantly in all diet groups, but there were no significant differences among the three diet groups in these changes.   

Of the 36 subjects with diabetes, only participants in the Mediterranean diet group experienced a significant reduction in fasting plasma glucose concentration (-32.8 mg/dL vs. +12.1 mg/dL in the low-fat diet group, p < 0.001).  Subjects without diabetes had no significant changes in glucose concentration. Insulin levels decreased significantly in subjects with and without diabetes in all diet groups and there were no significant differences among groups.  The HOMA-IR decreased significantly more in subjects with diabetes assigned to the Mediterranean diet than those in the low-fat diet group (-2.3 vs. -0.3, p = 0.04).  Glycosylated hemoglobin in participants with diabetes decreased in all groups (-0.4, -0.5, and -0.9% for low-fat, Mediterranean , and low-carbohydrate diet groups, but there were no significant differences among groups). 

Conclusions:  The results from this trial suggest that both the Mediterranean diet and the low-carbohydrate diet may be safe and effective alternatives to a low-fat diet.  In addition to producing weight loss, the low-carbohydrate diet had a more favorable net effect on the fasting lipid profile and the Mediterranean diet appeared to have some advantages for subjects with diabetes.  These differences suggest that personal dietary preferences and metabolic goals should be considered when selecting a weight loss plan.

Citations:

¹Krauss RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: revision 2000; a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 2000;102:2284-2299.

²Willett WC, Skerrett PJ. Eat, drink, and be healthy: The Harvard Medical School guide to healthy eating. New York : Simon & Schuster, 2001.

³Atkins RC. Dr. Atkins’ new diet revolution. New York : Avon , 2002.

Dr. Maki’s Commentary:  The results from this study confirm those from previous trials in several respects. They demonstrate that either a moderate-fat (Mediterranean) diet or a higher-fat, low-carbohydrate diet (Atkins) are effective alternatives to a traditional low-fat diet for weight loss and weight loss maintenance.  The results from this study are consistent with those from a trial we conducted¹ in which we compared a low-fat, portion-controlled diet to a reduced glycemic load diet (The South Beach Diet) that was similar to the Mediterranean diet used in this trial.

The influences of different diets on the cardiovascular risk profile are also of interest.  An often expressed concern is that the higher intakes of saturated fat and cholesterol associated with lower carbohydrate diets will increase total and low-density lipoprotein cholesterol levels.  This does not appear to be the case.  The low-density lipoprotein cholesterol level does not appear to be increased on a low-carbohydrate diet compared with a low-fat diet, despite higher consumption of saturated fat and cholesterol.  However, Krauss and colleagues showed that higher saturated fat intake in the context of a low carbohydrate diet is associated with a higher level of low-density lipoprotein cholesterol when compared to a similarly low carbohydrate diet with a lower intake of saturated fat.²  Additional research is warranted to explore the mechanisms responsible for the large decline in low-density lipoprotein cholesterol associated with a low carbohydrate, low saturated fat/cholesterol diet compared with a typical American diet.

What are the implications of these results for clinical practice?  First, it appears that individuals can be successful losing weight and maintaining weight loss on a range of macronutrient intakes, although the amount of weight loss after 24 months was modest in all groups.  Therefore, a patient’s personal preference should be taken into account when weight loss counseling occurs.  Some people prefer a lower fat diet and some prefer a lower carbohydrate diet and patients should not be pushed to follow a diet that is substantially different from their personal preferences.

Second, for individuals with insulin resistance and/or glucose intolerance, moderate carbohydrate restriction seems to be a reasonable approach.  Reducing carbohydrate intake has been consistently associated with lower levels of triglycerides and a more favorable total/high-density lipoprotein cholesterol ratio.  There is also some reason to believe that moderate restriction of carbohydrate intake may reduce demand on the pancreas for insulin secretion.  This might slow the development of beta-cell dysfunction, although clinical trials are needed to test this hypothesis.

Finally, in my view, some legitimate concerns remain regarding the use of very low carbohydrate diets.  Data from population studies suggest that higher intakes of whole grains, nuts and fruits are associated with lower mortality and reduced incidence rates for cancer, diabetes and heart disease.  Such foods can be incorporated into moderately carbohydrate restricted diets (40% of energy or more), but their intakes are necessarily limited on very low carbohydrate diets.  Furthermore, intakes of foods that have been associated with increased risks for cancer, diabetes and heart disease, such as high-fat and processed meats tend to be higher on such diets.  Therefore, while I feel that many individuals with obesity, insulin resistance or dyslipidemia may benefit from some reduction in carbohydrate intake, with greater emphasis on unsaturated fats and proteins,³ I remain uncomfortable with diets that contain less than roughly 40% of energy from carbohydrate.  

Citations:

¹Maki KC, Rains TM, Kaden VM, Raneri KR, Davidson MH. Effects of a reduced-glycemic-load diet on body weight, body composition, and cardiovascular disease risk markers in overweight and obese adults. Am J Clin Nutr 2007;85:724-734.

²Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 2006;83:1025-1031.

³Furtado JD, Campos H, Appel LJ, Miller ER, Laranjo N, Carey VJ, Sacks FM. Effect of protein, unsaturated fat, and carbohydrate intakes on plasma apolipoprotein B and VLDL and LDL containing apolipoprotein C-III: results from the OmniHeart Trial.  Am J Clin Nutr 2008;87:1623-1630.

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