what is the effect of changes in body fat on dyslipidemia · what is the effect of changes in body...

What is the Effect of Changes in Body Fat on Dyslipidemia

Eric C. Westman, M.D. M.H.S.Duke University Medical Center

Durham, North [email protected]

Associate Professor of MedicinePresident, Obesity Medicine Association (formerly ASBP)

Director, Duke Lifestyle Medicine ClinicCourse Director, Medical Management of Obesity

Fellow, The Obesity SocietyAuthor of The New Atkins for a New You

Variable Mean ± SD

Initial weight (kg) 98.5 ± 17.6

Initial body mass index 34.8 ± 6.2

Weight loss (kg) 16.6 ± 12.6

Final % ideal body weight 125.8 ± 10.1

Final body mass index 27.8 ± 3.2

Dattilo, Kris-Etherton. Effects of Weight Reduction on Blood Lipids and Lipoproteins: a Meta-analysis. Am J Clin Nutr 1992;56:320-8.

Initial Body Weight Indices and Change in Body Weight Indices for Effects of Weight Reduction on Blood Lipids

and Lipoproteins

Before After ChangePercent Change

Total Chol (mmol/l) 5.93 5.14 -0.79 -13.3%

LDL-C (mmol/l) 3.44 3.05 -0.39 -11.3%

HDL-C (mmol/l) 1.17 1.08 -0.09 -0.8%

TAG (mmol/l) 2.05 1.39 -0.66 -32.2%

Effects of Weight Reduction on Blood Lipids and Lipoproteins

Dattilo, Kris-Etherton. Effects of Weight Reduction on Blood Lipids and Lipoproteins: a Meta-analysis. Am J Clin Nutr 1992;56:320-8.

Outpatient LCKD Randomized Controlled Trials: Design

Reference Design Setting Patients Duration Visits

Sondike 2003 RCT Clinic Healthy teens 3m q2Wk

Brehm 2003 RCT Clinic Healthy adults 6m q2Wk x 6, then @

6mo

Samaha 2003 Stern 2004 RCT Clinic Outpt

adults 6m 12m qWk x 4, then monthly

Foster 2003 RCT Clinic Healthy adults 12m

q2Wk x 2, q4Wk x 4,then Wk 26, 34, 42, 52

Yancy 2004 RCT Clinic Healthy adults 6m q2Wks x 6, then

monthlyBrinkworth 2009 RCT Clinic Healthy

adults 12 m q2Wks x 4, then monthly

Nordmann et al. Arch Intern Med 2006;166:285-293.

Low Fat Low Carbohydrate

Ref Duration Weight LDL Trig HDL Weight LDL Trig HDL

Sondike 3 mo -4.1kg -17%* -6% +2% -9.9kg* +4% -48%* +4%n=30

Brehm 6 mo -3.9kg† -5% +2% +8% -8.5kg*† 0% -23%* +13%n=42

Samaha/ 6 mo -1.9kg† +3% -4% -2% -5.8kg*† +4% -20%* 0%Stern 12 mo -3.1kg -3% +2% -12% -5.1kg +6% -29% -2%n=132

Foster 6 mo -5.3kg† -3% -13% +4% -9.7kg*† +4% -21% +20%*n=63 12 mo -4.5kg† -6% +1% +3% -7.3kg† +1% -28%* +18%*

Yancy 6 mo -6.5kg -3% -15% -1% -12.0kg* +2% -42%* +13%*n=119

Brinkworth 12 mos -11.5kg +3% -12% 0% -14.5kg +3% -35% +21%N=40

Outpatient LCKD RCTs: Weight Loss and Serum Lipids

* p<0.05 for between-groups comparison

Effect on Fasting Lipid Subfractions

0

0.5

1

1.5

2

2.5

3

Large VLDL

Intermed VLDL

Small VLDL

Large LDL

Small LDL

Large HDL*10

Small HDL*10

LDLP*100

Baseline (n=43)Week 24 (n=43)

0

0.5

1

1.5

2

2.5

3

Large VLDL

Intermed VLDL

Small VLDL

Large LDL

Small LDL

Large HDL*10

Small HDL*10

LDLP*100

mg/

dl

Baseline (n=35)Week 24 (n=35)

LOW CARBOHYDRATE DIET PGMLOW FAT DIET GROUP

*

*

*

*

* p < 0.05 for comparison between groups

Seshadri et al. Am J Med 2004;117:398-405 (subanalysis of Samaha/Stern)

*

Effect on Fasting Lipid Subfractions

0

20

40

60

80

100

120

140

Large VLDL

Intermed VLDL

Small VLDL IDL

Large LDL

Intermed LDL

Small LDL

Large HDL

Small HDL

Baseline (n=36)Week 6 (n=36)Week 12 (n=36)Week 24 (n=36)

0

20

40

60

80

100

120

140

Large VLDL

Intermed VLDL

Small VLDL IDL

Large LDL

Intermed LDL

Small LDL

Large HDL

Small HDL

mg/

dl

Baseline (n=27)Week 6 (n=27)Week 12 (n=27)Week 24 (n=27)

LOW CARBOHYDRATE DIET PGMLOW FAT DIET GROUP

*

*

*

*

* p < 0.05 for comparison between groups

Westman et al. Int J Cardiol 2006;110:212-216. (subanalysis of Yancy)

2 months (“efficacy”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H

Atkins 40 1736 137g 93.5 89.5 -3.6 kg +1.3 -32.3 +3.2 -0.18Zone 40 1434 157 90.4 54.5 -3.8 kg -9.7 -54.1 +1.8 -0.33WWatchers 40 1615 191 80.5 54.5 -3.5 kg -12.1 -9.2 -0.2 -0.42Ornish 40 1393 230 70.0 27.5 -3.6 kg -16.5 -0.4 -3.6 -0.21

Popular Diet Effects on Weight Loss and Cardiac Risk Factors

Dansinger ML et al. JAMA 2005;293:43-53.

12 months (“effectiveness”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL L/H

Atkins 40 1886 190g 86.0 80.5 -2.1 kg -7.1 -1.2 +3.4 -0.39Zone 40 1757 173 90.4 71.5 -3.2 kg -11.8 -2.5 +3.3 -0.52WWatchers 40 1832 208 82.5 64.0 -3.0 kg -9.3 -12.7 -3.4 -0.55Ornish 40 1819 218 76.5 64.0 -3.3 kg -12.6 +5.6 -0.5 -0.31

“To approximate the realistic long-term sustainability of each diet, we asked participants to follow their dietary assignment to the best of their ability to their 2 month assessment, after which time we encouraged them to follow their assigned diet according to their own self-determined interest level.”

2 months (“efficacy”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP

Atkins 77 1381 ~62g 97 84 -4.3 kg +2.3 -52.3 -0.4 -2.9Zone 79 1455 152 87 57 -2.0 kg -5.3 -24.8 -0.5 -2.1LEARN 79 1476 180 73 49 -2.8 kg -7.3 -17.2 -3.8 -1.4Ornish 76 1408 220 60 33 -2.8 kg -10.1 -10.9 -5.3 -0.4

Popular Diet Effects on Weight Cardiac Risk Among Women

Gardner CD et al. JAMA 2007;297:969-977.

12 months (“effectiveness”)

Group n kcal/d CHO PRO FAT Weight LDL Trig HDL DBP

Atkins 77 1599 ~140g 84 78 -4.5 kg +0.8 -29.3 +4.9 -4.4Zone 79 1594 179 80 62 -1.5 kg 0 -4.2 +2.2 -2.1LEARN 79 1654 194 79 61 -2.5 kg +0.6 -14.6 -2.8 -2.2Ornish 76 1505 195 68 50 -2.4 kg -3.8 -14.9 0 -0.7

“Each diet group attended 1-hour classes led by a registered dietician once per week for 8 weeks and covered approximately one eighth of their respective books per class...Efforts to maximize retention included email and telephone reminders…and incentive payments.”

Effect of Diet Programs on Metabolic Syndrome ParametersFrom Baseline to 12 Months

Atkins Zone LEARN Ornish P

(n=77) (n=79) (n=79) (n=76) value

BMI, kg/m2 -1.65 -0.53 -0.92 -0.77 .01

Waist-hip ratio -0.019 -0.013 -0.009 -0.012 .10

HDL-C, mg/dL +4.9 +2.2 +2.8 0.0 0.002

Triglycerides, mg/dL -29.3 -4.2 -14.6 -14.9 0.01

Non-HDL-C, mg/dL -5.1 -0.5 -4.0 -6.8 0.36

Insulin, U/mL -1.8 -1.5 -1.8 -0.2 0.17

Glucose, mg/dL -1.8 -1.6 +0.5 -0.8 0.54

Diastolic b.p., mmHg -4.4 -2.1 -2.2 -0.7 0.009

Systolic b.p., mmHg -7.6 -3.3 -3.1 -1.9 <0.001

Gardner CD et al. JAMA 2007;297:969-977.

Low Carb vs. Low Fat Diet + OrlistatStudy Design

146 overweight VA outpatient volunteers146 overweight VA outpatient volunteers

Low Fat Diet + Orlistat• group meetings for 48 wks• exercise recommendation• multivitamin daily• Orlistat (Xenical™) 120 mg

three times a day

Low Fat Diet + Orlistat• group meetings for 48 wks• exercise recommendation• multivitamin daily• Orlistat (Xenical™) 120 mg

three times a day

Low Carb Ketogenic Diet• group meetings for 48 wks• exercise recommendation• multivitamin daily

Low Carb Ketogenic Diet• group meetings for 48 wks• exercise recommendation• multivitamin daily

RR

Yancy et al. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. Arch Intern Med 2010;170:136-145.

Mean % Weight Change Over Time*

n= 74 71 66 65 60 61 69 61 52 53 46 54 65n= 72 64 58 58 51 50 57 48 43 54 41 40 57

Low Carbohydrate Diet

Orlistat + Low Fat Diet

Low Carb Ketogenic Diet vs. Orlistat + Low Fat Diet Serum Lipids at 24 Weeks

Low Carb Ketogenic Diet Orlistat + Low Fat Diet

Wk 0 Wk 24 Change Wk 0 Wk 24 Change

Total Chol (mg/dl) 181.5 183.4 +1.6% 185.0 167.8 -9.3%

LDL-C (mg/dl) 115.6 123.7 +7.0% 118.1 104.2 -11.8%

HDL-C (mg/dl) 37.6 41.0 +10.6% 39.1 39.4 +0.7%

TAG (mg/dl) 142.2 100.0 -29.7% 139.1 118.0 -15.2%

CRP (mg/l) 0.60 0.53 -11.7% 0.8 0.75 -6.3%

Non HDL-C 143.9 142.4 -1.0% 145.9 128.4 -12.0%

TAG/HDL 3.78 2.43 -35.7% 3.56 2.99 -16%

Yancy et al. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. Arch Intern Med 2010;170:136-145.

Tay J et al. Metabolic Effects of Weight Loss on a Very-Low-Carbohydrate Diet Compared With an Isocaloric High-Carbohydrate Diet in Abdominally Obese Subjects. JACC 2008;51:59–67.

Cardiovascular Risk Markers After 24 weeks on a Very Low Carb Diet or an Energy Matched HC diet

VLCHF HCLFWk 24 Change Wk 24 Change p value

Body weight (kg) 88.1 -12.0 89.9 -11.5 0.57

BMI (kg/m2) 30.0 -4.0 30.9 -4.0 0.74

Waist circumference (cm) 100.5 -10.6 103.2 -9.1 0.25

Total FFM (kg) 58.8 -1.7 57.7 -1.9 0.66

Total FM (kg) 29.1 -10.2 32.2 -9.6 0.64

FM-to-FFM ratio (kg/kg) 0.5 -0.2 0.6 -0.1 0.76

Tay J et al. Metabolic Effects of Weight Loss on a Very-Low-Carbohydrate Diet Compared With an Isocaloric High-Carbohydrate Diet in Abdominally Obese Subjects. JACC 2008;51:59–67.

Serum Lipids Before and After a 24-Week Dietary Intervention

VLCHF HCLFWk 0 Wk 24 Change Wk 0 Wk 24 Change

Total Chol (mmol/l) * 5.39 5.37 -0.02 5.39 4.85 -0.54

LDL-C (mmol/l) * 3.24 3.19 0.06 3.26 2.80 -0.46

HDL-C (mmol/l) * 1.42 1.67 0.25 1.33 1.41 0.08

TAG (mmol/l) * 1.60 0.96 -0.64 1.78 1.43 -0.35

Non HDL-C * 3.97 3.70 -0.27 4.06 3.44 -0.62

ApoB (g/l) 0.98 0.96 -0.02 1.00 0.95 -0.05

Carbohydrate Restriction Treats Metabolic Syndrome

• Volek JS, Feinman RD. Carbohydrate restriction improves the features of Metabolic Syndrome: Metabolic syndrome may be defined by the response to carbohydrate restriction. Nutr Metab 2005;2:31.

• Feinman RD, Volek JS. Carbohydrate restriction as the default treatment for type 2 diabetes and metabolic syndrome. Scand Cardiovasc J 2008;42:256-63.

• Accurso A et al. Dietary carbohdyrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal. Nutr Metab 2008;5:9.

• Volek JS, Fernandez ML, Feinman RD, Phinney SD. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res 2008;47:307-18.

• Volek JS et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009;44:297-309.

Transient Hypercholesterolemia of Weight Loss

Effects of Diet, 5 kg Weight Loss

N = 178All malesBMI 29 kg/m2

Triacylglycerol (log mg/dL)

Krauss et al. AJCN 2006;83:1025-31.



Apo B (mg/dL)




LDL IV


Saturated Fat

Saturated Fat

Metabolic Processing of Saturated Fat

Low Carbohydrate

Diet (45 g CHO/d)

Low Fat Diet

(208 g CHO/d)

Saturated Fat Synthesis

Saturated Fat Intake

(12 g/d)



(36 g/d)

Forsythe et al. Lipids. 43(1):65-77, 2008

Saturated Fat

Saturated Fat

Metabolic Processing of Saturated Fat

Less Saturated Fat Burned

as Fuel

More Saturated Fat Burned

as Fuel

Low Carbohydrate

Diet (45 g CHO/d)

Low Fat Diet

(208 g CHO/d)



(12 g/d)


Forsythe et al. Lipids. 43(1):65-77, 2008


(36 g/d)

Does Insulin Reduction Explain Changes in Lipoproteins after Body Fat Loss?

Kennedy AR et al. A high fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 2007, February 13.

Relationship Between Large VLDL and Small LDL

Packard C et al. Int J Card 2000;74:S17–S22.

Small LDL

Large VLDL

Triglycerides > 133 mg/dl

Dietary Carbohydrate, Large VLDL and Small LDL

Small LDL

Large VLDL

Triglycerides > 133 mg/dl

Dietary CHO

Volek JS, Feinman RD. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutrition & Metabolism 2005, 2:31.

0

50

100

150

200

250

300

350

March May July Sept Nov Jan

Bod

y W

eigh

t (lb

s)

TRIG

HDL

WEIGHT

CPAP d/c’dSpironolactone, coumadin d/c’d

Weight Loss, Improvements in Lipids

A 50 year old white female with obesity (BMI = 31.3) wants to lose weight.

Fasting lab tests:

Date BMI Wt (lbs) Chol Trig LDL HDL Non HDL

6/10 31.3 178 245 247 141 54 191

Initiation of Carbohydrate Restricted Diet

8/10 29.1 164

2/11 24.5 141

5/11 23.5 138 209 46 119 81 128

Summary

• There is considerable variability in the effect of fat mass loss on serum lipoproteins.

• During the fat mass loss process, measurement of serum lipoproteins may not reflect the steady state after weight stability.

• Low fat, low calorie diets lower cardiovascular risk factors by mainly lowering LDL-C; low carbohydrate diets lower cardiovascular risk factors by mainly lowering triglyceride and raising HDL-C.

• The dietary pattern and loss of body fat both can influence dyslipidemia.

What is the Effect of Changes in Body Fat on Dyslipidemia

Eric C. Westman, M.D. M.H.S.Duke University Medical Center

Durham, North [email protected]

Associate Professor of MedicinePresident, Obesity Medicine Association (formerly ASBP)

Director, Duke Lifestyle Medicine ClinicCourse Director, Medical Management of Obesity

Fellow, The Obesity SocietyAuthor of The New Atkins for a New You

what is the effect of changes in body fat on dyslipidemia · what is the effect of changes in body...

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