Volume 6, Issue 2

Provident News

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Staff Announcements

Congratulations to Dr. Kevin C. Maki for recently being named a Fellow of the National Lipid Association (FNLA). This award is reserved for top leaders at the regional or national level for outstanding contributions in education, research, or practice in clinical llipidology.

Dr. Maki was also named to the Board of Directors of the Accreditation Council for Clinical Lipidology, which is the certifying body for non-physician, mid-level practitioners in clinical lipidology. 

Nicholas Shera, PhD is welcomed by Provident to the medical writing team.

 

Anya Boisvert is welcomed by Provident to the Glen Ellyn staff as Office Assistant.

 

Jocelyn Shields was promoted to Project Manager/Clinical Research Associate in the Glen Ellyn office. 

 

Robyn Krueger has transitioned from a part-time to a full-time Provident employee as a Project Assistant.  We are excited to have her on board.

 

Tia Kartsanov and her husband, Nick, are expecting their fifth child in November.  Congratulations to the Kartsanov family!

 

Luisa Ochoa, Laboratory Technician, is expecting a baby girl. Congratulations!

 

Rachel Hubacher, Project Manager in the Glen Ellyn office, has become engaged to be married.  Congratulations!

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Recent and Upcoming Publications

Maki KC, Rains TM, Dicklin MR, Bell M.  Repeatability of indices of insulin sensitivity and secretion from standard liquid meal tests in subjects with type 2 diabetes mellitus, normal and impaired fasting glucose.  Diabetes Technol Ther.  2010 (in press). 

Rains TM, Agarwal S, Maki KC.  Anti-obesity effects of green tea catechins: A mechanistic review.  J Nutr Biochem.  2010 (in press).

Bays HE, Maki KC, Schmitz K.  The Bile Acid Sequestrant Acceptability validation study.  Intl J Clin Pract. 2010 (in press).

Maki KC, Dicklin MR, Davidson MH, Doyle RT, Ballantyne CM for the COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators.  Baseline lipoprotein lipids and the low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl esters added to simvastatin therapy.  Am J Cardiol.  2010;  105:1409-1412.

Bays HE, Maki KC, McKenney J, Snipes R, Meadowcroft A, Schroyer R, Doyle RT, Stein E. Long-term, up to 24 month, efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients.  Curr Med Res Opin.  2010;26:907-915.

Alish CJ, Garvey WT, Maki KC, Sacks G, Hustead DS, Hegazi RA, Mustad VA.  A diabetes-specific enteral formula improves glycemic variability in patients with type 2 diabetes.  Diabetes Technol Ther.  2010;12:419-425.

 

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Recent and Upcoming Abstracts/Presentations

National Lipid Association – Lipid Management Training Course.  Pharmacologic therapies and treatment guidelines. Maki KC. August, 2010.

National Lipid Association – Lipid Management Training Course.  Advanced risk assessment and management of residual risk. Maki KC. August, 2010.

National Lipid Association – Masters in Lipidology Course.  Cardiovascular disease epidemiology and risk assessment.  Maki KC.  August, 2010.

National Lipid Association – Scientific Sessions – 2010.  A plant sterol/stanol supplement in tablet form lowers LDL and non-HDL cholesterol in men and women with primary hypercholesterolemia.  Maki KC, Lawless A, Reeves MS, Dicklin MR, Jenks BH, Shneyvas E, Brooks J.  May, 2010.

National Lipid Association – Scientific Sessions – 2010.  Effects of an insoluble fraction of soy protein vs. milk protein on plasma lipids and fecal bile acids in men and women with hypercholesterolemia.  Maki KC, Butteiger DN, Rains TM, Lawless A, Reeves MS, Schasteen C, Krul ES.  May, 2010. 

National Lipid Association – Scientific Sessions – 2010.  Stability of lipid responses to prescription omega-3 acid ethyl esters plus simvastatin over two years.  Maki KC, Harris WS, Lubin BC, Reeves MS, Dicklin MR.  May, 2010.

National Lipid Association – Scientific Sessions – 2010.  Predictors of anterior and posterior wall carotid intima media thickness progression in men and women at moderate risk of coronary heart disease.  Maki KC, Davidson MH, Dicklin MR, Bell M.  May, 2010.

National Lipid Association – Scientific Sessions – 2010.  Effects of vitamin D supplementation on 25-hydroxyvitamin D and markers of cardiovascular disease risk in subjects with high waist circumference.  Maki KC, Rubin MR, Wong LG, McManus JF, Jensen CD, Hubacher R, Lawless A.  May, 2010.

National Lipid Association.  Maki KC.  Cardiovascular disease epidemiology and risk assessment. Masters in Lipidology Advanced Training and Board Review Course.  May, 2010. 

National Lipid Association – Scientific Sessions – 2010.  The ins and outs of interpreting the statistical methodology and results of a clinical trial.  Maki KC. May, 2010.

American Society for Nutrition – 9th Vahouhy Dietary Fiber Symposium.  Measurement techniques for insulin sensitivity.  Maki KC. June, 2010.

Missouri, Nebraska, Kansas Beef Council Nutrition Adventure.  Recent advances in dietary management of dyslipidemias. Maki KC.  May, 2010.

Institute of Food Technologists – Annual Meeting + Food Expo.  Ensuring quality control in human nutrition clinical trials through Good Clinical Practices.  Maki KC.  July, 2010.

Institute of Food Technologists – Annual Meeting + Food Expo.  The impact of dietary fibers on insulin sensitivity.  Maki KC.  July, 2010.
 

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In the Literature

Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid). New Engl J Med. 2010;362:1563-1574.
Authors: The ACCORD Study Group 

Objective and Methods:  

The National Heart, Lung, and Blood Institute’s (NHLBI) Action to Control Cardiovascular Risk in Diabetes (ACCORD) study evaluated the effects of intensive versus standard treatment of blood glucose combined with either intensive or standard treatment of lipids (n = 5518) or blood pressure (n = 4733) on cardiovascular outcomes (nonfatal myocardial infarction, stroke, or death from cardiovascular disease) in participants with type 2 diabetes.  The intensive glucose intervention was stopped early due to discovery of a higher mortality in the intensive therapy (targeting a glycated hemoglobin level below 6% compared to a target of 7.0-7.9%) group after 3.5 years of follow-up.1

Participants in the lipid study had low-density lipoprotein cholesterol (LDL-C) levels of 60-180 mg/dL; high-density lipoprotein cholesterol levels (HDL-C) below 50 mg/dL, except for women or black subjects where the HDL-C criterion was <55 mg/dL; and triglycerides <400 or <750 mg/dL (with and without lipid therapy, respectively).  Subjects received standard open label simvastatin 20 mg or 40 mg daily (40 mg for those with coronary heart disease) with titration to 40 mg during the trial if LDL-C was >100 mg/dL on any two occasions, or if the subject experienced a cardiovascular event.  After one month, participants were randomized to receive either the blinded fenofibrate 54 mg or 160 mg daily (based on the estimated glomerular filtration rate) or placebo. 

Results:   

Of the 5518 participants in ACCORD Lipid, 2765 received intensive lipid intervention (simvastatin plus fenofibrate) and 2753 received standard lipid therapy (simvastatin plus placebo). The mean duration of the follow-up period was 4.7 years and average daily dosages of simvastatin were essentially the same at 22.3 mg and 22.4 mg in the intensive and standard therapy groups, respectively. Mean LDL-C was reduced from 100.0 to 81.1 mg/dL with fenofibrate and 101.1 to 80.0 mg/dL with placebo (p = 0.16 between groups). Mean HDL-C increased from 38.0 to 41.2 mg/dL in the fenofibrate group and from 38.2 to 40.5 mg/dL in the placebo group (p = 0.01 between groups). Median triglyceride levels decreased from 164 to 122 mg/dL in the fenofibrate group and from 160 to 144 mg/dL in the placebo group (p < 0.001 between groups).

The annual rate of first occurrence of a cardiovascular event in the fenofibrate group was 2.2% versus 2.4% in the placebo group (P = 0.32).  In the subgroup of participants who had triglyceride levels in the highest tertile (≥204 mg/dL) and HDL-C in the lowest tertile (≤34 mg/dL), the annual rate of the primary outcome was 12.4% in the intensive therapy group  versus 17.3% in the standard therapy group when compared to all other participants (p = 0.057 for interaction).  Overall, men appeared to benefit from fenofibrate but a trend toward harm was noted among women (p = 0.01 for interaction).  However, the trend toward harm in women was not present in the subset with high triglycerides and low HDL-C.

Conclusions: 

Intensive lipid intervention utilizing combination simvastatin and fenofibrate in subjects with type 2 diabetes did not reduce the rates of cardiovascular events when compared to simvastatin monotherapy.  Routine use of simvastatin plus fenofibrate to further reduce cardiovascular events in the majority of high-risk patients with type 2 diabetes is not supported by these data.   

Dr. Maki’s Commentary:  

The results of ACCORD Lipid are not a surprise. They parallel those from other studies of fibrate therapy that suggest potential benefit among subjects with elevated triglycerides, or elevated triglycerides with low HDL-C, and little or no benefit among subjects without elevated triglycerides.2 The predominant effects of fibrates on the lipoprotein profile are to reduce the circulating concentrations of triglycerides and triglyceride-rich lipoproteins, and to raise HDL-C. Eight large-scale cardiovascular event trials of fibrate therapy have been completed.2-5 In all of the trials that employed one of the two fibrates currently available in the U.S. (fenofibrate and gemfibrozil), including the Helsinki Heart Study, the Veterans Affairs HDL Intervention Trial (VA-HIT), the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, and ACCORD Lipid, the same pattern of greater benefit among subjects with hypertriglyceridemia (or hypertriglyceridemia with low HDL-C) was observed.  
  
The findings from ACCORD Lipid therefore underline three important points.  First, subjects with “atherogenic dyslipidemia” (i.e., with high triglycerides and low HDL-C) and diabetes are at very high risk for a cardiovascular event.  Among subjects assigned to simvastatin plus placebo, the event rate was 17.4% among those with the atherogenic dyslipidemia pattern, compared to 2.4% in the entire group.  Second, given that approximately one-third of the US population has fasting triglycerides above the normal range (i.e., ≥150 mg/dL),6 there is an urgent need for clinical trials to provide information on the risks and benefits of treatment options for hypertriglyceridemia.  Third, since the pattern of greater benefit of fibrate therapy in subjects with hypertriglyceridemia, compared to those without hypertriglyceridemia, has been known for more than 20 years,7 the time is long overdue for a trial of fibrate therapy in subjects with hypertriglyceridemia.
  

Citations:  

1.  The ACCORD Study Group. Effects of Intensive Glucose Lowering in Type 2 Diabetes. New Engl J Med. 2008;358:2545-2559.  

2.  Maki KC. Fibrates for the treatment of metabolic syndrome. Current Atherosclerosis Reports. 2004;6:45-51.  

3.  Meade T, Zuhrie R, Cook C, et al. Bezafibrate in men with lower extremity arterial disease: randomized controlled trial. BMJ. 2002;325:1139-1143.

4.  Keech A, Simes RJ, Barter P, et al. FIELD Study Investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomized controlled trial. Lancet. 2005;366:1849-1861.   

5.  The ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. New Engl J Med. 2010;362:1563-1574.  

6.  Ford ES, Li C, Zhao G, et al. Hypertriglyceridemia and its pharmacologic treatment among US adults. Arch Int Med. 2009;169:572-578.  

7.  Manninen V, Elo O, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. J Am Med Assoc. 1998;260:641-651. 

 

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Books and Book Chapters

 
  • Kevin C Maki, PhD, President of Provident Clinical Research & Consulting, Inc., has recently launched Provident Business Press, a publishing division.  His latest book, Tipping the Odds for the Entrepreneur: Big Ideas On Success For The Small Business Owner, is now available for purchase at www.TippingTheOdds.com, in both perfect bound book and as an E-Book (PDF).  Please take a moment to visit this website which is devoted to helping people achieve their personal and financial goals and follow Dr. Maki’s blogs on various business related topics. 

 
  • Maki KC, Rubin M. Cardiovascular Epidemiology and Characterization of Atherosclerotic Disease Risk Factors.  In: Toth PP, Cannon CP (eds).  Comprehensive Cardiovascular Care in the Primary Care Setting, Humana Press, 2010 (in press).

 

                     

 

 

  • Toth PP, Maki KC. Practical Lipid Management: London: John Wiley & Sons.  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 is available for purchase at Amazon.com.

 

     

              

     

     

     

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

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  • 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, 2nd 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.

 

 

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