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Low glycemic diet for weight loss in hypertriglyceridemic patients attending a lipid clinic
Journal of Clinical Lipidology (2010) 4, 508–514
Low glycemic diet for weight loss in hypertriglyceridemic patients attending a lipid clinic Westly A. Bailey, MD, Eric C. Westman, MD, MHS, Megan L. Marquart, MPH, RD, LDN, John R. Guyton, MD* Duke University Medical Center, Box 3510, Durham, NC 27710, USA (Drs. Bailey, Westman, and Guyton); and Banner Baywood Medical Center, Mesa, AZ (Dr. Marquart) KEYWORDS: Weight loss; Glycemic index; Low glycemic diet; Triglycerides; High density lipoproteins; Lipid clinic
PURPOSE: To assess the effectiveness of low glycemic dietary counseling for weight loss among moderately hypertriglyceridemic patients in an academic referral lipid clinic. METHODS: During 1998 to 2000, weight loss advice followed traditional guidelines. Beginning in 2001, hypertriglyceridemic patients were advised to greatly reduce intake of high glycemic carbohydrates. The clinic database was queried for all patients initiating consultative treatment from 1998 through 2004. Subjects were included if initial fasting triglyceride was 200 to 800 mg/dL and if at least two follow-up visits were made during a period of 365 days or more. Mean percent changes from baseline in weight and lipid/lipoproteins beyond 1 year were calculated. Macronutrient composition was determined 3- to 5-day food diaries submitted by subjects from the highest quartile of weight loss. RESULTS: Patients (n 5 56) first seen in 1998-2000 had 0.2 6 0.7% mean weight gain beyond one year compared with 3.0 6 0.5% weight loss for patients (n 5 141) initially seen in 2001 to 2004 (P , .001 comparing groups). Weight loss correlated with triglyceride reduction (22.6 mg/dL per kilogram body weight, r 5 0.29, P ,.001) and with HDL-C increase (0.22 mg/dL per kilogram body weight, r 5 0.16; P 5.038). Highest quartile weight losers in the low glycemic group (n 5 15) reported consuming 44% carbohydrate calories, 32% fat, 22% protein, and 2% alcohol. CONCLUSION: Hypertriglyceridemic patients who received low glycemic dietary counseling and maintained clinic attendance more than 1 year achieved mean 3.0% weight loss. This was improved compared with historical controls with traditional dietary counseling. Food diaries from successful weight losers suggested compliance with a low glycemic, moderately reduced carbohydrate diet plan. Ó 2010 National Lipid Association. All rights reserved.
Most patients with hypertriglyceridemia are overweight or obese and can benefit from weight reduction. Randomized clinical trials employing a variety of intervention protocols have established that medically significant weight loss can be achieved and sustained for 1 year in research study participants.1–11 Although randomized trials provide guidance for weight loss counseling, the value of specific interventions must * Corresponding author. E-mail address: [email protected] Submitted May 8, 2010. Accepted for publication August 18, 2010.
remain in question until they are assessed in actual clinical practice. Research studies attract motivated subjects, and study participation itself provides motivation for diet and lifestyle change. The strategies that work among intensively counseled and/or motivated research study participants may differ from strategies found to be successful in brief intervention in a busy clinic. Results quantifying weight loss among patient cohorts in the medical clinic setting are scant. Traditional weight loss advice emphasizes overall caloric restriction, specific restriction of fat calories to 30% or less of total calories, portion control, and behavior modification as
1933-2874/$ - see front matter Ó 2010 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2010.08.019
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Low glycemic diet for weight loss
ways to change caloric balance.4,12–14 Newer results suggest that low-carbohydrate diets may be equally or more effective for weight loss at 6 months4,15 and at or beyond 1 year6,10 compared with traditional low-fat diets. In patients with hypertriglyceridemia, reduction of dietary carbohydrate may be particularly helpful because isocaloric substitution of carbohydrate by fat and protein has long been known to reduce plasma triglyceride.16 Computerized records of weight, lipid and lipoprotein assays, and lipid treatment have been maintained in the Duke Lipid Clinic since 1993. Until 2001, long-term weight loss in hypertriglyceridemic patients seemed to occur rarely, despite persistent traditional advice given to patients. In 2001, the advice given to patients shifted to emphasize a low glycemic diet that sought to eliminate sugared drinks and markedly reduce refined carbohydrate staples such as bread and white potatoes. The present study examines weight change beyond one year and its correlates in plasma lipoprotein changes in this academic referral lipid clinic from 1998 through September 12, 2005. In addition, we analyzed food diaries to assess by self-report the dietary composition achieved by successful weight losers.
509 encouraged to increase fiber intake, especially viscous (soluble) fiber, but not if this meant adding new calories to the diet. Unless limited by musculoskeletal or cardiorespiratory problems, all patients were advised to devote at least 2 hours per week to aerobic exercise such as brisk walking. Dietary advice was provided to patients by the supervising clinic physician (J.R.G.) and by experienced mid-level providers. With the aid of four handout sheets covering the principles described previously, dietary counseling required 10 to 15 minutes at the initial clinic visit. Dietary assessment and counseling generally required 2 to 10 minutes at return visits. Drug treatment of lipid disorders in the clinic followed recommendations of the National Cholesterol Education Program (NCEP). Patients with persistent serum triglyceride levels greater than 500 mg/dL were generally prescribed a fibric acid derivative, whereas those with triglyceride 200 to 499 mg/dL and high non-HDL cholesterol usually received a statin. Additional pharmacologic/nutritional therapies included niacin and fish oil. Reasons for termination of lipid clinic attendance were not assessed in detail but included in some cases the attainment of lipid goals before 1 year had elapsed.
Inclusion criteria
Materials and methods Database Weights, lipid panels, and lipid-modifying medications have been entered routinely into a computer database for all patients in the Duke Lipid Clinic since 1993.
Clinic practice In 2001, providers at the clinic began to advise patients with moderate hypertriglyceridemia (2002800 mg/dL) to make high glycemic foods (glycemic index [GI] of 70 or greater) ‘‘rare’’ in their diet or to ‘‘greatly reduce’’ them, and to ‘‘limit and reduce’’ moderate glycemic foods (GI of 50269). Glycemic index of foods was determined by averaging several online sources that followed the methods of Jenkins et al.17 A single page listing of 160 foods and food categories arranged in 3 columns of low, medium, and high glycemic categories was provided (available from one of the authors; J.R.G.). Reduction of overall dietary intake was advised, with a focus especially on sugared drinks and starchy carbohydrates. Replacement of these foods by high-fat items was not advised. Foods high in animal fat were omitted from the printed list. Except under unusual circumstances, initial dietary advice included a weight loss target of 10 pounds, or sometimes 10 to 15 pounds, during a period of 6 months. Patients were encouraged to track their weight to gauge the required strictness of high glycemic carbohydrate reduction. Other dietary advice included avoidance of trans fat and preference for polyunsaturated and monounsaturated fat over saturated fat. Patients were
Patients initiating treatment in the clinic from January 1, 1998, through September 12, 2004, were screened for baseline serum triglyceride levels of 200 to 800 mg/dL and for a prolonged course of observation including at least two follow-up clinic visits over a minimum of 365 days.
Data analyses Mean percent change in body weight beyond 1 year, defined as the mean percent change over all visits $365 days, was the primary outcome variable. Initial analysis suggested a marked difference in weight change between patients initially seen in 1998 to 2000 (n 5 56) and those initially seen in 2001 to 2004 (n 5 141). For analyses of weight time course and distribution of weight change, subjects were divided by the time of the initial visit into Group 1 from 1998 to 2000 and Group 2 from 2001 to 2004. Percent changes from baseline in weight, triglycerides, total cholesterol, highdensity lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were calculated for all patients. Comparisons were made by the use of Student’s t test and nonparametric analyses as appropriate. Correlations between long-term parameter changes also were computed. All statistical analyses were performed by the use of Microsoft Office Excel 2003 (Redmond, WA) and SAS Statistical Software, Version 9.1.3 (SAS Institute Inc., Cary, NC).
Food records We identified subjects from Group 2 (initial clinic visit in 200122004) from the lowest and highest quartiles of long-term weight change. They were mailed a recruitment
510 Baseline demographic data
Year of initial visit Number Age, mean 6 SD Weight, pounds, mean 6 SD Follow-up, years, mean 6 SD Race, n (%) White African American Native American Asian Gender Male/female, n
199822000 (Group 1)
200122004 (Group 2)
56 53.6 6 12.2 194.4 6 32.3 4.0 6 2.0
141 54.4 6 11.6 189.2 6 36.6 2.2 6 1.1
49 (87.5) 5 (8.9) 2 (3.6)
128 9 2 2
37/19
(90.8) (6.4) (1.4) (1.4)
6
Percent Weight Change
Table 1
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80/61
4 2 0 -2 -4 -6
1998
1999
2000
2001
2002
2003
2004
Year of Initial Visit
Research approval The Duke University Institutional Review Board approved all phases of this research. No procedures, tests, or interventions were performed for research purposes.
Results A total of 441 patients had baseline triglyceride 200 to 800 mg/dL at their initial clinic visit in the period January 1, 1998, to September 12, 2005. Among these, 197 patients met the additional criteria of a minimum of two follow-up visits extending 1 year or longer and were included in this study. Mean body mass index (BMI) at baseline was 30.1 6 4.7 kg/m2 (6SD). Obesity (BMI $30 kg/m2) was present in 48% of patients, 37% were overweight with BMI $25 and ,30 kg/m2, and 15% had BMI less than 25 kg/m2. Patients were mostly male and, their race was predominantly white (Table 1). Mean duration of follow-up was 4.0 years for patients initially seen in 1998 to 2000 and 2.2 years for patients initially seen in 2001–2004 (Table 1). Mean percent weight loss beyond 1 year was analyzed according to the calendar year of the initial clinic visit. Results supported the hypothesis that effectiveness of weight loss improved in 2001 (Fig. 1), when dietary advice shifted to the recommendation for a low glycemic diet. The consistency of weight loss for patients initiated in 2001–2004, compared with lack of effectiveness before 2001, supported the allocation of subjects to Group 1, initiating in 1998 to 2000, versus
Figure 1 Weight change beyond 12 months by year of initial consultation. Mean percent weight change was computed for all visits beyond 12 months of initial visit. The graph represents averages for seven patient groups, each differing by year of first visit.
Group 2, initiating in 2001 to 2004. Mean weight loss beyond 1 year was 20.2 6 0.7% (mean 6 SEM) in Group 1, signifying a slight weight gain, versus 3.0 6 0.5% weight loss in Group 2 (P , .001). The time course of weight loss in the 2 groups during the course of 24 months of follow-up is shown in Figure 2. The two groups diverged within 6 months, were clearly different by 12 months, and trended in opposite directions in the second year. Figure 3 shows the distribution of weight changes among the 197 patients. Approximately one-half (52%) of Group 1 patients experienced weight gain beyond 1 year versus 31% in Group 2. Conversely, 6% or greater weight loss was achieved by 25% of Group 2 patients versus 14% in Group 1. To characterize the diet actually followed by successful weight losers, we analyzed 3- to 5-day food diaries from Group 2 patients in the highest quartile of weight loss. Table 2 shows that successful weight losers consumed a diet moderately low in carbohydrate at 44% of total calories
Percent Weight Change
letter describing informed consent; diet logs; and metered return envelope. A portion estimation guide sheet from a commercial weight loss website was also included.18 We requested 3- to 5-day diet logs including at least one weekend day. A total of 19 diet logs were returned, but the logs representing the lowest quartile of weight loss were not analyzed further because of the small number (n 5 4) as well as unrealistically low total daily energy intake (mean 1374 Kcal). Diet logs were analyzed by the use of Nutritionist ProÔ, Version 2.2 (First DataBank Inc., San Bruno, CA).
4 3 2 1 0 -1 -2 -3 -4 -5
0
1-3
4-6
7-9
10-12 13-15 16-18 19-21 22-24
Months Figure 2 Percent weight change by interval and group. Mean percent weight change was computed for each patient who returned within the specified 3-month intervals. Group means with standard errors are plotted over eight intervals. 6 5 Group 1; - 5 Group 2.
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Low glycemic diet for weight loss
511 Table 3 Lipid and lipoprotein levels and percent changes (mean 6 SEM)
Percent of Subjects
60
Group 1
50 40 30 20 10 0 Gained
Lost 0-2%
Lost 2-4%
Lost 4-6%
Lost 6-8%
Lost 8-10%
Lost >10%
Weight Change Categories
Figure 3 Distributions of long-term weight change by group. A total of 54 patients from group 1 and 134 subjects from group 2 were categorized by weight change beyond 12 months. This plot illustrates the fraction of subjects from each group who met certain weight criteria. Open bars, Group 1; solid bars, Group 2.
while deriving 32% of calories from fat (13% from saturated fat), 22% from protein, and 2% from ethanol. The mean proportions of calories from foods of varying GI were as follows: low (GI 0249), 51%; medium (GI 50269), 31%; and high (GI 702100), 18%. Table 3 shows baseline lipid and lipoprotein levels and the mean percent changes beyond 1 year. Groups 1 and 2 did not differ at baseline. Reductions in total cholesterol, triglyceride, and LDL-C were similar, whereas HDL-C tended to increase more in Group 2, approaching statistical significance. Medications administered to improve plasma lipoprotein levels are shown in Table 4. Among the four classes of medications known to reduce plasma triglyceride levels, the use of fibrates was somewhat lower in Group 2, but the difference was not statistically significant. Among all patients, weight loss correlated significantly with triglyceride reduction (r 5 0.29, P , .001) and with
P value
Group 2
Baseline TC, mg/dL 266.4 6 11.4 TG, mg/dL 416.9 6 20.1 LDL-C, mg/dL 139.8 6 10.5 HDL-C, mg/dL 40.8 6 1.5 Percent change beyond 1 year TC 217.5 6 3.2 TG 231.5 6 6.3 LDL-C 217.5 6 6.1 HDL-C 14.2 6 2.9
259.0 387.8 155.8 41.6
6 6 6 6
5.9 13.3 6.9 1.1
.62 .42 .28 .96
218.4 233.6 215.6 22.2
6 6 6 6
1.9 4.1 5.2 3.0
.79 .78 .81 .053
HDL-C, high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride.
HDL-C increase (r 5 0.16; P 5 .038), but not with LDL-C change. The slope of the regression line showed the magnitude of triglyceride reduction to be 2.6 mg/dL for each kilogram of weight lost. Likewise, HDL-C increased by 0.22 mg/ dL for each kilogram of weight lost. The effect of weight loss on triglyceride reduction was examined further by categorizing all patients into subgroups who gained weight, lost 0% to 2.99% body weight, lost 3% to 5.99%, or lost 6% or greater. Figure 4 shows that those who gained weight had marginal triglyceride reduction averaging 12.4% at their final observed visit, whereas those who lost weight achieved 42.3% triglyceride reduction. HDL cholesterol increases were greater among patients who lost 6% or more body weight, averaging 29.0% in this group compared with12.6% among weight gainers. These results did not appear to be the result of differential use of medications because patients in each subgroup averaged approximately 1.5 triglyceridelowering medications (Fig. 4, bottom panel).
Discussion Table 2 Macronutrient profile of successful (highest quartile) weight losers in Group 2 (mean 6 SD) compared with recommendations of the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III)25 This study (n 5 15) Total calories, kcal Protein, % kcal Carbohydrate, % kcal Total fat, % kcal Saturated fat, % kcal Monounsaturated fat, % kcal Polyunsaturated fat, % kcal Ethanol, % kcal Fiber, g/day Sugar, g/day
1769 22.0 44.0 32.1 12.6 12.8
6 6 6 6 6 6
450 4.0 10.6 7.4 4.6 3.7
6.7 6 2.0 1.9 6 6.9 20.8 6 9.6 58.1 6 29.8
NR, no specific recommendation.
NCEP-ATP III recommendations NR w15 50260 25235 ,7 #20 #10 ‘‘In moderation’’ 20-30 NR
This study has analyzed temporal trends in weight loss outcomes in a lipid clinic where brief dietary counseling was given by medical providers. In 2001 dietary advice shifted to emphasize a low glycemic approach that seeks to largely eliminate the consumption of high glycemic foods such as bread and white potatoes. Concurrent with the shift in advice, weight loss beyond 1 year of clinic follow-up improved from essentially no weight loss to an average 3% of initial body weight.
Table 4 Final pharmacologic profiles (% of patients taking the drug class)
Group 1 Group 2
Fibrate
Fish oil (.3 g/d)
Niacin
Statin
36 26
26 24
45 42
57 64
512
Journal of Clinical Lipidology, Vol 4, No 6, December 2010
MEAN PERCENT TRIGLYCERIDE CHANGE
0 -10 -20 -30 -40 -50
40
MEAN PERCENT HDLC CHANGE
35 30 25 20 15 10 5
MEAN NUMBER OF TRIG-LOWERING DRUGS
0
2.0 1.5 1.0 0.5 0.0 WGT GAIN (N=69)
0-2.9% WGT LOSS (N=43)
3-5.9% WGT LOSS (N=38)
≥6% WGT LOSS (N=43)
Figure 4 Triglyceride change, HDL-C change, and mean number of triglyceride-lowering drugs according to weight loss achievement among all subjects.
Cardiovascular risk has traditionally been approached through treatment of specific risk factors such as hypertension and LDL cholesterol. Increasingly, the impact of excess adiposity on a variety of risk factors encompassed by the metabolic syndrome has been recognized as a driver of cardiovascular risk. Consequently much effort in metabolic, pharmaceutical, and clinical research today is directed at the goal of reducing adiposity. Behaviorally oriented diet trials have shown success in fostering long-term (1 year) weight reductions up to 8.6%. However, the more successful trials have involved intensive counseling often beginning at weekly or biweekly intervals. A much less-intensive, low-cost approach was studied by Foster et al.,4 who provided self-study materials to 63 subjects. In their study, mean percent weight loss at 1 year was 4.4% in subjects advised to follow a low carbohydrate ketogenic diet and 2.5% in subjects advised to follow a low fat diet. Dietary trials with more intensive counseling
(minimally four 1-hour visits over the first 2 months) have achieved 1-year weight reductions of 2.3% to 8.6%, depending on study group demographics and varying intervention plans.1–3,5–9 A meta-analysis of short-term randomized trials suggested that low glycemic diets achieve greater weight loss than comparison diets over periods up to 6 months.19 However, one trial not included in the meta-analysis provided food to participants during the course of 6 months with identical caloric restriction in a high glycemic, 60% carbohydrate diet versus a low glycemic, 40% carbohydrate diet.9 This trial found no difference in weight loss. Moreover, clinical trials lasting 36 weeks or longer have not reported weight loss advantages for low glycemic diets.8,10,20,21 Ebbeling et al8 found that plasma insulin concentration determined 30 minutes after an oral glucose load predicted greater effectiveness of a low glycemic diet in producing weight loss. Hypertriglyceridemic patients are known to have elevated insulin levels, including insulin concentrations determined 30 minutes after an oral glucose load.22,23 This might make our subjects more likely to respond to a low glycemic diet with weight loss, although the exact relationship to insulin resistance remains to be determined. The average 3.0% weight loss beyond 1 year reported here is not directly comparable with results reported from clinical trials because we evaluated only those patients who continued in clinical follow-up. A few patients were excluded from this study because the treatment program, sometimes including substantial weight loss, attained lipid goals in less than a year, prompting discharge from the clinic. However, most patients who did not reach 1 year of follow-up did so because of canceled or missed appointments, and it is likely that these were not as successful at weight loss. Therefore, weight reduction judged by intention to treat would likely be considerably less than 3.0%. Despite this limitation, temporal improvement in weight loss outcomes occurred in 2001 concurrent with new weight loss advice. In a literature search, we found no comparable data for weight loss as a component of medical treatment for dyslipidemia in clinical practice. Therefore, our data provide at least an initial benchmark for weight loss outcomes that may be readily computed in other medical clinics with suitable electronic records. Maintenance of weight reduction has been a problem in almost all studies of behavioral and pharmaceutical intervention. Our data for Group 1 (initiating treatment in 199822000) exemplify the pattern of worsening outcomes after the first 9 months of intervention (Fig. 2). Group 2 (initiating in 200122004) showed a notable persistence of weight reduction and even a trend toward improvement extending into the second year. Factors responsible for this result might include (1) the fact that the patient is given full responsibility for making dietary changes from the outset without initial intensive support, so that worsening upon withdrawal of the support does not occur, (2) the fact that patients continue to receive professional advice and encouragement at a steady, though limited, rate, (3) enthusiasm on
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Low glycemic diet for weight loss
the part of the supervising physician and clinic staff, (4) the possibility that some patients do not ‘‘get the message’’ initially, but first begin to lose weight late in the treatment period, so that aggregate results give the impression of persistence, and (5) the possibility that less successful weight losers leave the clinic somewhat earlier than successful weight losers, although 1-year follow-up was an inclusion criterion. Continuing personal contact (aforementioned factors 2 and 3) has been shown to be helpful in maintenance of weight loss.24 Overall, we cannot distinguish among these possibilities from our data, but the apparent persistence of weight loss is encouraging. We estimated the macronutrient composition of diets followed by successful (highest quartile) weight losers in Group 2 from 3- to 5-day diet logs. The estimated calories from carbohydrate (44% of total calories) were below the range of 50% to 60% of total calories recommended by NCEP guidelines25 but not as low as ketogenic low carbohydrate diets (#10%).15 Therefore, the low glycemic dietary program used here is not the same as low carbohydrate programs that received attention in the early 2000s,2,4,26 but it is similar to recently reported low glycemic programs.8,9,20,21,27 In addition, our program relies on simple choices (ie, emphasizing exclusion of foods rather than portion control), eliminates most beverage calories, and advises avoidance of certain foods that deliver a large fraction of total calories in the usual U.S. diet (breads and other readily digested starches). Saturated fat as a percentage of total calories was 12.6%, greater than the NCEP recommendation of less than 7% of total calories. This outcome may reflect the fact that our low glycemic dietary advice gave greater allowance to animal fat than to starchy carbohydrates. Weight loss responses remained highly variable from one individual to another—an unmet practical challenge. Among Group 2 patients counseled on the low glycemic diet, almost one-third actually gained weight, whereas onequarter achieved more than 6% weight loss. This variability provided an opportunity to observe an empirical relation between weight loss achieved and lipid modification. The estimated effects on triglyceride and HDL cholesterol, determined by linear regression of the changes in these parameters on body weight changes, were 22.6 mg/dL (0.029 mmol/L) and 0.22 mg/dL (0.006 mmol/L), respectively, per kilogram decrease in body weight. These results were not likely to be attributable to the differential use of medication because the number of lipid medications used by patients did not differ by weight loss achievement. In a meta-analysis of randomized clinical trials, Dattilo and Kris-Etherton28 found that triglyceride levels change by a mean 21.3 mg/dL (0.015 mmol/L) and HDL cholesterol levels increase by a mean 10.35 mg/dL (0.009 mmol/L) for every kg of long-term body weight reduction. Our data are similar and thus confirm that the predicted effects of weight loss on triglyceride and HDL, determined from randomized trials, can be observed in clinical practice. The practical impact of weight loss on lipoproteins may be clarified further by examining the mean responses by
513 weight loss categories (Fig. 4). The difference in percent triglyceride reduction between those who lost weight beyond 1 year and those who gained was 30%. This is effect similar to that of high-dose fish oil or of niacin on triglyceride and approximately two-thirds of the effect of fibric acid derivatives.29–32 The impact of weight reduction on HDL cholesterol was a difference of 16% between weight gainers and the best weight losers. This is comparable with the HDL-increasing effects of exercise, alcohol, fibric acid derivatives, or moderate doses of niacin.30,33 We did not observe a difference in plasma triglyceride levels between Group 1 patients receiving traditional dietary advice and Group 2 patients receiving low glycemic dietary advice, but we did observe a trend toward greater HDL cholesterol levels favoring Group 2 (P 5 .053). In randomized trials, Maki et al20 and Jenkins et al34 found that low glycemic diets increased HDL cholesterol. Ebbeling et al8 found that triglyceride and HDL cholesterol improved more from a low glycemic load diet over 6 to 18 months, but LDL cholesterol was lower on a low fat diet. The authors of other trials found no difference in lipid and lipoprotein parameters,9,21 but Wolever and colleagues21 found a significant 30% reduction in C-reactive protein in diabetic patients assigned to a low glycemic diet. Taken together, the data suggest a possible advantage in cardiovascular risk for the low glycemic diet. This observational study has substantial limitations. Given our interest in long-term weight-loss outcomes, analysis was restricted to patients who continued to attend the clinic more than 1 year. Because of limited time and resources available, we did not try to contact or to obtain weights from patients who did not return to the clinic. Moreover, such a strategy of renewed contact would require informed consent, impractical in a retrospective study that extended back more than 8 years in time. A further limitation of this study is the use of historical controls, as secular trends may have influenced weight loss outcomes apart from the dietary advice we provided. Nevertheless, the manner of recording of patient visits and weights in the computer database did not change during the entire time period, and substantial improvement in weight loss for long-term patients was documented over an 8 year period. As a historical trend per se this is of interest, and the evidence points toward, but does not prove, low glycemic dietary advice as a possible explanation. The chief aim of new medical knowledge should be its application in clinical practice, and knowledge should be regarded as incomplete until its effects are observed in a ‘‘real-world’’ setting. This is especially true for lifestyle research because research protocols for behavioral modification are inherently selective and motivating and are often too intensive and expensive for widespread practical application. By documenting an improvement in the attainment of weight loss and its correlates for lipid management in a routinely monitored clinic setting, this study’s advantages help to offset its major limitation of incomplete follow-up.
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References
19. Thomas DE, Elliott EJ, Baur L. Low glycaemic index or low glycaemic load diets for overweight and obesity. Cochrane Database Syst Rev. 2007; CD005105. 20. Maki KC, Rains TM, Kaden VN, 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. 21. Wolever TM, Gibbs AL, Mehling C, et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemicindex dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Am J Clin Nutr. 2008;87:114–125. 22. Reaven GM, Mejean L, Villaume C, Drouin P, Debry G. Plasma glucose and insulin responses to oral glucose in nonobese subjects and patients with endogenous hypertriglyceridemia. Metabolism. 1983; 32:447–450. 23. Byrne CD, Wareham NJ, Brown DC, et al. Hypertriglyceridaemia in subjects with normal and abnormal glucose tolerance: relative contributions of insulin secretion, insulin resistance and suppression of plasma non-esterified fatty acids. Diabetologia. 1994;37: 889–896. 24. Svetkey LP, Stevens VJ, Brantley PJ, et al. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. J Am Med Assoc. 2008;299:1139–1148. 25. Adult Treatment Panel III. Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Bethesda, MD: NIH Publication No. 02-5215, National Institutes of Health; 2002. 26. Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE. Effect of 6-month adherence to a very low carbohydrate diet program. Am J Med. 2002;113:30–36. 27. McMillan-Price J, Petocz P, Atkinson F, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006;166:1466–1475. 28. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56: 320–328. 29. Harris WS, Ginsberg HN, Arunakul N, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997;4: 385–391. 30. Guyton JR, Blazing MA, Hagar J, et al. Extended-release niacin versus gemfibrozil for treatment of low levels of high density lipoprotein cholesterol. Arch Intern Med. 2000;160:1177–1184. 31. Brown WV, Dujovne CA, Farquhar JW, et al. Effects of fenofibrate on plasma lipids. Double-blind, multicenter study in patients with type IIA or IIB hyperlipidemia. Arteriosclerosis. 1986;6:670–678. 32. Goldberg AC, Schonfeld G, Feldman EB, et al. Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study. Clin Ther. 1989;11: 69–83. 33. Bowen PH, Guyton JR. Nonpharmacologic and pharmacologic treatment of patients with low levels of high-density lipoprotein cholesterol. Curr Atheroscler Rep. 2000;2:58–63. 34. Jenkins DJ, Kendall CW, Keown-Eyssen G, et al. Effect of a lowglycemic index or a high-cereal fiber diet on type 2 diabetes: a randomized trial. J Am Med Assoc. 2008;300:2742–2753.
1. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403. 2. Stern L, Iqbal N, Seshadri P, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year followup of a randomized trial. Ann Intern Med. 2004;140:778–785. 3. Pi-Sunyer X, Blackburn G, Brancati FL, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care. 2007;30: 1374–1383. 4. Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a lowcarbohydrate diet for obesity. N Engl J Med. 2003;348:2082–2090. 5. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. J Am Med Assoc. 2005;293:43–53. 6. Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. J Am Med Assoc. 2007;297:969–977. 7. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a lowcarbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008; 359:229–241. 8. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial. J Am Med Assoc. 2007;297:2092–2102. 9. Das SK, Gilhooly CH, Golden JK, et al. Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. Am J Clin Nutr. 2007;85:1023–1030. 10. Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859–873. 11. Shai I, Spence JD, Schwarzfuchs D, et al. Dietary intervention to reverse carotid atherosclerosis. Circulation. 2010;121:1200–1208. 12. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Bethesda: National Institutes of Health; 1998. 13. Eckel RH. Clinical practice. Nonsurgical management of obesity in adults. N Engl J Med. 2008;358:1941–1950. 14. Thompson WG, Cook DA, Clark MM, Bardia A, Levine JA. Treatment of obesity. Mayo Clin Proc. 2007;82:93–101. 15. Yancy WS Jr., Olsen MK, Guyton JR, Bakst RP, Westman EC. A lowcarbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004; 140:769–777. 16. Reissell PK, Mandella PA, Poon-King TMW, Hatch FT. Treatment of hypertriglyceridemia. Am J Clin Nutr. 1966;19:84–98. 17. Jenkins DJ, Wolever TM, Kalmusky J, et al. Low glycemic index carbohydrate foods in the management of hyperlipidemia. Am J Clin Nutr. 1985;42:604–617. 18. Internet communication Avaialble at: http://www.jennycraig.com.au/? event5toolsResources.subs&sub5PortionSize_VisualCues. Accessed January 15, 2008. Similar visual cues available at: http://www.bcm. edu/cnrc/consumer/archives/portioncues.htm. Accessed September 10, 2010.
Low glycemic diet for weight loss in hypertriglyceridemic patients attending a lipid clinic Westly A. Bailey, MD, Eric C. Westman, MD, MHS, Megan L. Marquart, MPH, RD, LDN, John R. Guyton, MD* Duke University Medical Center, Box 3510, Durham, NC 27710, USA (Drs. Bailey, Westman, and Guyton); and Banner Baywood Medical Center, Mesa, AZ (Dr. Marquart) KEYWORDS: Weight loss; Glycemic index; Low glycemic diet; Triglycerides; High density lipoproteins; Lipid clinic
PURPOSE: To assess the effectiveness of low glycemic dietary counseling for weight loss among moderately hypertriglyceridemic patients in an academic referral lipid clinic. METHODS: During 1998 to 2000, weight loss advice followed traditional guidelines. Beginning in 2001, hypertriglyceridemic patients were advised to greatly reduce intake of high glycemic carbohydrates. The clinic database was queried for all patients initiating consultative treatment from 1998 through 2004. Subjects were included if initial fasting triglyceride was 200 to 800 mg/dL and if at least two follow-up visits were made during a period of 365 days or more. Mean percent changes from baseline in weight and lipid/lipoproteins beyond 1 year were calculated. Macronutrient composition was determined 3- to 5-day food diaries submitted by subjects from the highest quartile of weight loss. RESULTS: Patients (n 5 56) first seen in 1998-2000 had 0.2 6 0.7% mean weight gain beyond one year compared with 3.0 6 0.5% weight loss for patients (n 5 141) initially seen in 2001 to 2004 (P , .001 comparing groups). Weight loss correlated with triglyceride reduction (22.6 mg/dL per kilogram body weight, r 5 0.29, P ,.001) and with HDL-C increase (0.22 mg/dL per kilogram body weight, r 5 0.16; P 5.038). Highest quartile weight losers in the low glycemic group (n 5 15) reported consuming 44% carbohydrate calories, 32% fat, 22% protein, and 2% alcohol. CONCLUSION: Hypertriglyceridemic patients who received low glycemic dietary counseling and maintained clinic attendance more than 1 year achieved mean 3.0% weight loss. This was improved compared with historical controls with traditional dietary counseling. Food diaries from successful weight losers suggested compliance with a low glycemic, moderately reduced carbohydrate diet plan. Ó 2010 National Lipid Association. All rights reserved.
Most patients with hypertriglyceridemia are overweight or obese and can benefit from weight reduction. Randomized clinical trials employing a variety of intervention protocols have established that medically significant weight loss can be achieved and sustained for 1 year in research study participants.1–11 Although randomized trials provide guidance for weight loss counseling, the value of specific interventions must * Corresponding author. E-mail address: [email protected] Submitted May 8, 2010. Accepted for publication August 18, 2010.
remain in question until they are assessed in actual clinical practice. Research studies attract motivated subjects, and study participation itself provides motivation for diet and lifestyle change. The strategies that work among intensively counseled and/or motivated research study participants may differ from strategies found to be successful in brief intervention in a busy clinic. Results quantifying weight loss among patient cohorts in the medical clinic setting are scant. Traditional weight loss advice emphasizes overall caloric restriction, specific restriction of fat calories to 30% or less of total calories, portion control, and behavior modification as
1933-2874/$ - see front matter Ó 2010 National Lipid Association. All rights reserved. doi:10.1016/j.jacl.2010.08.019
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ways to change caloric balance.4,12–14 Newer results suggest that low-carbohydrate diets may be equally or more effective for weight loss at 6 months4,15 and at or beyond 1 year6,10 compared with traditional low-fat diets. In patients with hypertriglyceridemia, reduction of dietary carbohydrate may be particularly helpful because isocaloric substitution of carbohydrate by fat and protein has long been known to reduce plasma triglyceride.16 Computerized records of weight, lipid and lipoprotein assays, and lipid treatment have been maintained in the Duke Lipid Clinic since 1993. Until 2001, long-term weight loss in hypertriglyceridemic patients seemed to occur rarely, despite persistent traditional advice given to patients. In 2001, the advice given to patients shifted to emphasize a low glycemic diet that sought to eliminate sugared drinks and markedly reduce refined carbohydrate staples such as bread and white potatoes. The present study examines weight change beyond one year and its correlates in plasma lipoprotein changes in this academic referral lipid clinic from 1998 through September 12, 2005. In addition, we analyzed food diaries to assess by self-report the dietary composition achieved by successful weight losers.
509 encouraged to increase fiber intake, especially viscous (soluble) fiber, but not if this meant adding new calories to the diet. Unless limited by musculoskeletal or cardiorespiratory problems, all patients were advised to devote at least 2 hours per week to aerobic exercise such as brisk walking. Dietary advice was provided to patients by the supervising clinic physician (J.R.G.) and by experienced mid-level providers. With the aid of four handout sheets covering the principles described previously, dietary counseling required 10 to 15 minutes at the initial clinic visit. Dietary assessment and counseling generally required 2 to 10 minutes at return visits. Drug treatment of lipid disorders in the clinic followed recommendations of the National Cholesterol Education Program (NCEP). Patients with persistent serum triglyceride levels greater than 500 mg/dL were generally prescribed a fibric acid derivative, whereas those with triglyceride 200 to 499 mg/dL and high non-HDL cholesterol usually received a statin. Additional pharmacologic/nutritional therapies included niacin and fish oil. Reasons for termination of lipid clinic attendance were not assessed in detail but included in some cases the attainment of lipid goals before 1 year had elapsed.
Inclusion criteria
Materials and methods Database Weights, lipid panels, and lipid-modifying medications have been entered routinely into a computer database for all patients in the Duke Lipid Clinic since 1993.
Clinic practice In 2001, providers at the clinic began to advise patients with moderate hypertriglyceridemia (2002800 mg/dL) to make high glycemic foods (glycemic index [GI] of 70 or greater) ‘‘rare’’ in their diet or to ‘‘greatly reduce’’ them, and to ‘‘limit and reduce’’ moderate glycemic foods (GI of 50269). Glycemic index of foods was determined by averaging several online sources that followed the methods of Jenkins et al.17 A single page listing of 160 foods and food categories arranged in 3 columns of low, medium, and high glycemic categories was provided (available from one of the authors; J.R.G.). Reduction of overall dietary intake was advised, with a focus especially on sugared drinks and starchy carbohydrates. Replacement of these foods by high-fat items was not advised. Foods high in animal fat were omitted from the printed list. Except under unusual circumstances, initial dietary advice included a weight loss target of 10 pounds, or sometimes 10 to 15 pounds, during a period of 6 months. Patients were encouraged to track their weight to gauge the required strictness of high glycemic carbohydrate reduction. Other dietary advice included avoidance of trans fat and preference for polyunsaturated and monounsaturated fat over saturated fat. Patients were
Patients initiating treatment in the clinic from January 1, 1998, through September 12, 2004, were screened for baseline serum triglyceride levels of 200 to 800 mg/dL and for a prolonged course of observation including at least two follow-up clinic visits over a minimum of 365 days.
Data analyses Mean percent change in body weight beyond 1 year, defined as the mean percent change over all visits $365 days, was the primary outcome variable. Initial analysis suggested a marked difference in weight change between patients initially seen in 1998 to 2000 (n 5 56) and those initially seen in 2001 to 2004 (n 5 141). For analyses of weight time course and distribution of weight change, subjects were divided by the time of the initial visit into Group 1 from 1998 to 2000 and Group 2 from 2001 to 2004. Percent changes from baseline in weight, triglycerides, total cholesterol, highdensity lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were calculated for all patients. Comparisons were made by the use of Student’s t test and nonparametric analyses as appropriate. Correlations between long-term parameter changes also were computed. All statistical analyses were performed by the use of Microsoft Office Excel 2003 (Redmond, WA) and SAS Statistical Software, Version 9.1.3 (SAS Institute Inc., Cary, NC).
Food records We identified subjects from Group 2 (initial clinic visit in 200122004) from the lowest and highest quartiles of long-term weight change. They were mailed a recruitment
510 Baseline demographic data
Year of initial visit Number Age, mean 6 SD Weight, pounds, mean 6 SD Follow-up, years, mean 6 SD Race, n (%) White African American Native American Asian Gender Male/female, n
199822000 (Group 1)
200122004 (Group 2)
56 53.6 6 12.2 194.4 6 32.3 4.0 6 2.0
141 54.4 6 11.6 189.2 6 36.6 2.2 6 1.1
49 (87.5) 5 (8.9) 2 (3.6)
128 9 2 2
37/19
(90.8) (6.4) (1.4) (1.4)
6
Percent Weight Change
Table 1
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80/61
4 2 0 -2 -4 -6
1998
1999
2000
2001
2002
2003
2004
Year of Initial Visit
Research approval The Duke University Institutional Review Board approved all phases of this research. No procedures, tests, or interventions were performed for research purposes.
Results A total of 441 patients had baseline triglyceride 200 to 800 mg/dL at their initial clinic visit in the period January 1, 1998, to September 12, 2005. Among these, 197 patients met the additional criteria of a minimum of two follow-up visits extending 1 year or longer and were included in this study. Mean body mass index (BMI) at baseline was 30.1 6 4.7 kg/m2 (6SD). Obesity (BMI $30 kg/m2) was present in 48% of patients, 37% were overweight with BMI $25 and ,30 kg/m2, and 15% had BMI less than 25 kg/m2. Patients were mostly male and, their race was predominantly white (Table 1). Mean duration of follow-up was 4.0 years for patients initially seen in 1998 to 2000 and 2.2 years for patients initially seen in 2001–2004 (Table 1). Mean percent weight loss beyond 1 year was analyzed according to the calendar year of the initial clinic visit. Results supported the hypothesis that effectiveness of weight loss improved in 2001 (Fig. 1), when dietary advice shifted to the recommendation for a low glycemic diet. The consistency of weight loss for patients initiated in 2001–2004, compared with lack of effectiveness before 2001, supported the allocation of subjects to Group 1, initiating in 1998 to 2000, versus
Figure 1 Weight change beyond 12 months by year of initial consultation. Mean percent weight change was computed for all visits beyond 12 months of initial visit. The graph represents averages for seven patient groups, each differing by year of first visit.
Group 2, initiating in 2001 to 2004. Mean weight loss beyond 1 year was 20.2 6 0.7% (mean 6 SEM) in Group 1, signifying a slight weight gain, versus 3.0 6 0.5% weight loss in Group 2 (P , .001). The time course of weight loss in the 2 groups during the course of 24 months of follow-up is shown in Figure 2. The two groups diverged within 6 months, were clearly different by 12 months, and trended in opposite directions in the second year. Figure 3 shows the distribution of weight changes among the 197 patients. Approximately one-half (52%) of Group 1 patients experienced weight gain beyond 1 year versus 31% in Group 2. Conversely, 6% or greater weight loss was achieved by 25% of Group 2 patients versus 14% in Group 1. To characterize the diet actually followed by successful weight losers, we analyzed 3- to 5-day food diaries from Group 2 patients in the highest quartile of weight loss. Table 2 shows that successful weight losers consumed a diet moderately low in carbohydrate at 44% of total calories
Percent Weight Change
letter describing informed consent; diet logs; and metered return envelope. A portion estimation guide sheet from a commercial weight loss website was also included.18 We requested 3- to 5-day diet logs including at least one weekend day. A total of 19 diet logs were returned, but the logs representing the lowest quartile of weight loss were not analyzed further because of the small number (n 5 4) as well as unrealistically low total daily energy intake (mean 1374 Kcal). Diet logs were analyzed by the use of Nutritionist ProÔ, Version 2.2 (First DataBank Inc., San Bruno, CA).
4 3 2 1 0 -1 -2 -3 -4 -5
0
1-3
4-6
7-9
10-12 13-15 16-18 19-21 22-24
Months Figure 2 Percent weight change by interval and group. Mean percent weight change was computed for each patient who returned within the specified 3-month intervals. Group means with standard errors are plotted over eight intervals. 6 5 Group 1; - 5 Group 2.
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511 Table 3 Lipid and lipoprotein levels and percent changes (mean 6 SEM)
Percent of Subjects
60
Group 1
50 40 30 20 10 0 Gained
Lost 0-2%
Lost 2-4%
Lost 4-6%
Lost 6-8%
Lost 8-10%
Lost >10%
Weight Change Categories
Figure 3 Distributions of long-term weight change by group. A total of 54 patients from group 1 and 134 subjects from group 2 were categorized by weight change beyond 12 months. This plot illustrates the fraction of subjects from each group who met certain weight criteria. Open bars, Group 1; solid bars, Group 2.
while deriving 32% of calories from fat (13% from saturated fat), 22% from protein, and 2% from ethanol. The mean proportions of calories from foods of varying GI were as follows: low (GI 0249), 51%; medium (GI 50269), 31%; and high (GI 702100), 18%. Table 3 shows baseline lipid and lipoprotein levels and the mean percent changes beyond 1 year. Groups 1 and 2 did not differ at baseline. Reductions in total cholesterol, triglyceride, and LDL-C were similar, whereas HDL-C tended to increase more in Group 2, approaching statistical significance. Medications administered to improve plasma lipoprotein levels are shown in Table 4. Among the four classes of medications known to reduce plasma triglyceride levels, the use of fibrates was somewhat lower in Group 2, but the difference was not statistically significant. Among all patients, weight loss correlated significantly with triglyceride reduction (r 5 0.29, P , .001) and with
P value
Group 2
Baseline TC, mg/dL 266.4 6 11.4 TG, mg/dL 416.9 6 20.1 LDL-C, mg/dL 139.8 6 10.5 HDL-C, mg/dL 40.8 6 1.5 Percent change beyond 1 year TC 217.5 6 3.2 TG 231.5 6 6.3 LDL-C 217.5 6 6.1 HDL-C 14.2 6 2.9
259.0 387.8 155.8 41.6
6 6 6 6
5.9 13.3 6.9 1.1
.62 .42 .28 .96
218.4 233.6 215.6 22.2
6 6 6 6
1.9 4.1 5.2 3.0
.79 .78 .81 .053
HDL-C, high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride.
HDL-C increase (r 5 0.16; P 5 .038), but not with LDL-C change. The slope of the regression line showed the magnitude of triglyceride reduction to be 2.6 mg/dL for each kilogram of weight lost. Likewise, HDL-C increased by 0.22 mg/ dL for each kilogram of weight lost. The effect of weight loss on triglyceride reduction was examined further by categorizing all patients into subgroups who gained weight, lost 0% to 2.99% body weight, lost 3% to 5.99%, or lost 6% or greater. Figure 4 shows that those who gained weight had marginal triglyceride reduction averaging 12.4% at their final observed visit, whereas those who lost weight achieved 42.3% triglyceride reduction. HDL cholesterol increases were greater among patients who lost 6% or more body weight, averaging 29.0% in this group compared with12.6% among weight gainers. These results did not appear to be the result of differential use of medications because patients in each subgroup averaged approximately 1.5 triglyceridelowering medications (Fig. 4, bottom panel).
Discussion Table 2 Macronutrient profile of successful (highest quartile) weight losers in Group 2 (mean 6 SD) compared with recommendations of the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III)25 This study (n 5 15) Total calories, kcal Protein, % kcal Carbohydrate, % kcal Total fat, % kcal Saturated fat, % kcal Monounsaturated fat, % kcal Polyunsaturated fat, % kcal Ethanol, % kcal Fiber, g/day Sugar, g/day
1769 22.0 44.0 32.1 12.6 12.8
6 6 6 6 6 6
450 4.0 10.6 7.4 4.6 3.7
6.7 6 2.0 1.9 6 6.9 20.8 6 9.6 58.1 6 29.8
NR, no specific recommendation.
NCEP-ATP III recommendations NR w15 50260 25235 ,7 #20 #10 ‘‘In moderation’’ 20-30 NR
This study has analyzed temporal trends in weight loss outcomes in a lipid clinic where brief dietary counseling was given by medical providers. In 2001 dietary advice shifted to emphasize a low glycemic approach that seeks to largely eliminate the consumption of high glycemic foods such as bread and white potatoes. Concurrent with the shift in advice, weight loss beyond 1 year of clinic follow-up improved from essentially no weight loss to an average 3% of initial body weight.
Table 4 Final pharmacologic profiles (% of patients taking the drug class)
Group 1 Group 2
Fibrate
Fish oil (.3 g/d)
Niacin
Statin
36 26
26 24
45 42
57 64
512
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MEAN PERCENT TRIGLYCERIDE CHANGE
0 -10 -20 -30 -40 -50
40
MEAN PERCENT HDLC CHANGE
35 30 25 20 15 10 5
MEAN NUMBER OF TRIG-LOWERING DRUGS
0
2.0 1.5 1.0 0.5 0.0 WGT GAIN (N=69)
0-2.9% WGT LOSS (N=43)
3-5.9% WGT LOSS (N=38)
≥6% WGT LOSS (N=43)
Figure 4 Triglyceride change, HDL-C change, and mean number of triglyceride-lowering drugs according to weight loss achievement among all subjects.
Cardiovascular risk has traditionally been approached through treatment of specific risk factors such as hypertension and LDL cholesterol. Increasingly, the impact of excess adiposity on a variety of risk factors encompassed by the metabolic syndrome has been recognized as a driver of cardiovascular risk. Consequently much effort in metabolic, pharmaceutical, and clinical research today is directed at the goal of reducing adiposity. Behaviorally oriented diet trials have shown success in fostering long-term (1 year) weight reductions up to 8.6%. However, the more successful trials have involved intensive counseling often beginning at weekly or biweekly intervals. A much less-intensive, low-cost approach was studied by Foster et al.,4 who provided self-study materials to 63 subjects. In their study, mean percent weight loss at 1 year was 4.4% in subjects advised to follow a low carbohydrate ketogenic diet and 2.5% in subjects advised to follow a low fat diet. Dietary trials with more intensive counseling
(minimally four 1-hour visits over the first 2 months) have achieved 1-year weight reductions of 2.3% to 8.6%, depending on study group demographics and varying intervention plans.1–3,5–9 A meta-analysis of short-term randomized trials suggested that low glycemic diets achieve greater weight loss than comparison diets over periods up to 6 months.19 However, one trial not included in the meta-analysis provided food to participants during the course of 6 months with identical caloric restriction in a high glycemic, 60% carbohydrate diet versus a low glycemic, 40% carbohydrate diet.9 This trial found no difference in weight loss. Moreover, clinical trials lasting 36 weeks or longer have not reported weight loss advantages for low glycemic diets.8,10,20,21 Ebbeling et al8 found that plasma insulin concentration determined 30 minutes after an oral glucose load predicted greater effectiveness of a low glycemic diet in producing weight loss. Hypertriglyceridemic patients are known to have elevated insulin levels, including insulin concentrations determined 30 minutes after an oral glucose load.22,23 This might make our subjects more likely to respond to a low glycemic diet with weight loss, although the exact relationship to insulin resistance remains to be determined. The average 3.0% weight loss beyond 1 year reported here is not directly comparable with results reported from clinical trials because we evaluated only those patients who continued in clinical follow-up. A few patients were excluded from this study because the treatment program, sometimes including substantial weight loss, attained lipid goals in less than a year, prompting discharge from the clinic. However, most patients who did not reach 1 year of follow-up did so because of canceled or missed appointments, and it is likely that these were not as successful at weight loss. Therefore, weight reduction judged by intention to treat would likely be considerably less than 3.0%. Despite this limitation, temporal improvement in weight loss outcomes occurred in 2001 concurrent with new weight loss advice. In a literature search, we found no comparable data for weight loss as a component of medical treatment for dyslipidemia in clinical practice. Therefore, our data provide at least an initial benchmark for weight loss outcomes that may be readily computed in other medical clinics with suitable electronic records. Maintenance of weight reduction has been a problem in almost all studies of behavioral and pharmaceutical intervention. Our data for Group 1 (initiating treatment in 199822000) exemplify the pattern of worsening outcomes after the first 9 months of intervention (Fig. 2). Group 2 (initiating in 200122004) showed a notable persistence of weight reduction and even a trend toward improvement extending into the second year. Factors responsible for this result might include (1) the fact that the patient is given full responsibility for making dietary changes from the outset without initial intensive support, so that worsening upon withdrawal of the support does not occur, (2) the fact that patients continue to receive professional advice and encouragement at a steady, though limited, rate, (3) enthusiasm on
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Low glycemic diet for weight loss
the part of the supervising physician and clinic staff, (4) the possibility that some patients do not ‘‘get the message’’ initially, but first begin to lose weight late in the treatment period, so that aggregate results give the impression of persistence, and (5) the possibility that less successful weight losers leave the clinic somewhat earlier than successful weight losers, although 1-year follow-up was an inclusion criterion. Continuing personal contact (aforementioned factors 2 and 3) has been shown to be helpful in maintenance of weight loss.24 Overall, we cannot distinguish among these possibilities from our data, but the apparent persistence of weight loss is encouraging. We estimated the macronutrient composition of diets followed by successful (highest quartile) weight losers in Group 2 from 3- to 5-day diet logs. The estimated calories from carbohydrate (44% of total calories) were below the range of 50% to 60% of total calories recommended by NCEP guidelines25 but not as low as ketogenic low carbohydrate diets (#10%).15 Therefore, the low glycemic dietary program used here is not the same as low carbohydrate programs that received attention in the early 2000s,2,4,26 but it is similar to recently reported low glycemic programs.8,9,20,21,27 In addition, our program relies on simple choices (ie, emphasizing exclusion of foods rather than portion control), eliminates most beverage calories, and advises avoidance of certain foods that deliver a large fraction of total calories in the usual U.S. diet (breads and other readily digested starches). Saturated fat as a percentage of total calories was 12.6%, greater than the NCEP recommendation of less than 7% of total calories. This outcome may reflect the fact that our low glycemic dietary advice gave greater allowance to animal fat than to starchy carbohydrates. Weight loss responses remained highly variable from one individual to another—an unmet practical challenge. Among Group 2 patients counseled on the low glycemic diet, almost one-third actually gained weight, whereas onequarter achieved more than 6% weight loss. This variability provided an opportunity to observe an empirical relation between weight loss achieved and lipid modification. The estimated effects on triglyceride and HDL cholesterol, determined by linear regression of the changes in these parameters on body weight changes, were 22.6 mg/dL (0.029 mmol/L) and 0.22 mg/dL (0.006 mmol/L), respectively, per kilogram decrease in body weight. These results were not likely to be attributable to the differential use of medication because the number of lipid medications used by patients did not differ by weight loss achievement. In a meta-analysis of randomized clinical trials, Dattilo and Kris-Etherton28 found that triglyceride levels change by a mean 21.3 mg/dL (0.015 mmol/L) and HDL cholesterol levels increase by a mean 10.35 mg/dL (0.009 mmol/L) for every kg of long-term body weight reduction. Our data are similar and thus confirm that the predicted effects of weight loss on triglyceride and HDL, determined from randomized trials, can be observed in clinical practice. The practical impact of weight loss on lipoproteins may be clarified further by examining the mean responses by
513 weight loss categories (Fig. 4). The difference in percent triglyceride reduction between those who lost weight beyond 1 year and those who gained was 30%. This is effect similar to that of high-dose fish oil or of niacin on triglyceride and approximately two-thirds of the effect of fibric acid derivatives.29–32 The impact of weight reduction on HDL cholesterol was a difference of 16% between weight gainers and the best weight losers. This is comparable with the HDL-increasing effects of exercise, alcohol, fibric acid derivatives, or moderate doses of niacin.30,33 We did not observe a difference in plasma triglyceride levels between Group 1 patients receiving traditional dietary advice and Group 2 patients receiving low glycemic dietary advice, but we did observe a trend toward greater HDL cholesterol levels favoring Group 2 (P 5 .053). In randomized trials, Maki et al20 and Jenkins et al34 found that low glycemic diets increased HDL cholesterol. Ebbeling et al8 found that triglyceride and HDL cholesterol improved more from a low glycemic load diet over 6 to 18 months, but LDL cholesterol was lower on a low fat diet. The authors of other trials found no difference in lipid and lipoprotein parameters,9,21 but Wolever and colleagues21 found a significant 30% reduction in C-reactive protein in diabetic patients assigned to a low glycemic diet. Taken together, the data suggest a possible advantage in cardiovascular risk for the low glycemic diet. This observational study has substantial limitations. Given our interest in long-term weight-loss outcomes, analysis was restricted to patients who continued to attend the clinic more than 1 year. Because of limited time and resources available, we did not try to contact or to obtain weights from patients who did not return to the clinic. Moreover, such a strategy of renewed contact would require informed consent, impractical in a retrospective study that extended back more than 8 years in time. A further limitation of this study is the use of historical controls, as secular trends may have influenced weight loss outcomes apart from the dietary advice we provided. Nevertheless, the manner of recording of patient visits and weights in the computer database did not change during the entire time period, and substantial improvement in weight loss for long-term patients was documented over an 8 year period. As a historical trend per se this is of interest, and the evidence points toward, but does not prove, low glycemic dietary advice as a possible explanation. The chief aim of new medical knowledge should be its application in clinical practice, and knowledge should be regarded as incomplete until its effects are observed in a ‘‘real-world’’ setting. This is especially true for lifestyle research because research protocols for behavioral modification are inherently selective and motivating and are often too intensive and expensive for widespread practical application. By documenting an improvement in the attainment of weight loss and its correlates for lipid management in a routinely monitored clinic setting, this study’s advantages help to offset its major limitation of incomplete follow-up.
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Journal of Clinical Lipidology, Vol 4, No 6, December 2010
References
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