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Lipid Effects of a Moderate Fat vs. Low Fat Diet among Free Living
Individuals with Metabolic Syndrome: DMetS Extension
Arthi Thirumalai, M.D.
Alice Dowdy M.S., Brian Fish, B.S., Robert H. Knopp, M.D., Pathmaja Paramsothy, M.D. M.S.
Global Purpose
To understand what diet is best and most feasible to decrease CVD risk factors among people with metabolic syndrome (MetS)
ObjectivesDetermine if the lipid improvements noted with a
moderate fat, moderate carbohydrate diet vs. low fat, high carbohydrate diet can be sustained under free-living conditions
Determine if free living people with MetS can adhere to prescribed diets on their own
The Problem: Metabolic Syndrome
30% of Americans have MetS
2 fold ↑ risk for CVD
Poor diet results in MetS
Weight loss is the ideal treatment but success rate is low
Refs: Grundy SM et al. Circulation. 2004;109:433-438, Lutsey P et al. Circulation. 2008;117:754-761. Gami AS et al. J Am Coll Cardiol. 2007;49:403-414
Metabolic Syndrome
Triglycerides ≥ 150 mg/dL PLUS 2 of:
HDL-C < 40 (men), < 50 mg/dL (women)
Blood Pressure ≥ 130/85 (or on antihypertensive meds)
Fasting Glucose > 100 mg/dL
Abdominal Obesity
Waist circumference >102 cm (men), > 88 cm (women)
Current Dietary Recommendations
Total fat 20-35%, total carbohydrate 45-65%
<10% saturated fat
Negligible trans fat
Insulin Resistant Populations such as those with MetS are not adequately addressed
What type of fats is unclear
Source: Dietary Guidelines for Americans, 2010
Maintaining free-living diets
No studies investigating the effects of a truly free-living diet on lipid effects or feasibility in MetS
Either employed food-exchange models or studied ad libitum diets in non-MetS patients
High drop-out rates: 12-40%
High tendency to not achieve dietary targets
Diets for Dyslipidemia in Metabolic Syndrome (DMetS)
Study Design: Double blinded, randomized, X-over
Intervention:
Moderate Fat (MF) = 40% fat, 45% carbohydrate
Low fat (LF) = 20% fat, 65% carbohydrate
Both diets 15% protein, 8% saturated fat, 25-30 g/day of fiber
Primary Lipid Outcome: Δ Non-HDL cholesterol from baseline
Also evaluated inflammatory markers, endothelial function, glycemic indices
Exclusion Criteria
LDL-C > 190 mg/dL
Triglyceride > 500 mg/dL
BP > 150/95 mmHg mean 2 visits
Use of lipid lowering rx other than statins
Moderate or high doses of thiazides or beta blockers previous 4 weeks
Use of plant sterols previous 4 weeks
Use of diabetes rx or fasting glucose level > 140 mg/dL
Hospitalization for CHD within 6 months
Summary Lipid Changes
DMetS: Results Summary
o First randomized controlled feeding study comparing LF vs. MF diet in MetS
o MF diet improves the atherogenic dyslipidemia of MetS compared with LF diet
o No significant difference in inflammatory markers, insulin sensitivity, or endothelial function
Study Design
Extension period:- 63 subjects (32 LF, 31 MF)- Weekly dietary sessions and counselling- Food records collected using 24 hour dietary recall
Statistical methods
Hypothesis 1: Subjects will be able to sustain their diet during the extension period as measured by lipid effectsPaired T-Tests
Hypothesis 2: The difference in effects of MF vs LF diets on atherogenic dyslipidemia of MetS will be maintained during the extension period Unpaired T-Tests
RESULTS
Baseline characteristics
Lipid outcomes Primary outcome: ∆ non-HDLc from end of
controlled feeding to end of free-living extension period
Secondary outcomes: ∆ Total cholesterol, ∆ triglycerides, ∆ HDLc, ∆ LDLc, ∆ Apo-B, ∆ Apo-A1
Adherence rates
Baseline characteristicsVariable Low Fat Moderate Fat P (MF vs LF)
Age (years) 55.7 51.9 0.06
Women 56% 48% 0.62
White race 88% 90% >0.99
BMI (kg/m2) 30.3 (4.09) 30.3 (4.93) 0.98
Waist Circumference (cm) 108 (14.8) 105 (18.5) 0.44
% meeting MetS definition of
HTN34% 29% 0.62
Triglycerides (mg/dL)* 232 [187,269] 181 [138,216] 0.02*
HDL Cholesterol (mg/dL) 38.9 (6.86) 40.7 (8.27) 0.35
Total Cholesterol (mg/dL) 203 (32.2) 189 (31.3) 0.09
Non-HDL Cholesterol (mg/dL)* 164 (29.9) 148 (30.2) 0.04*
LDL Cholesterol (mg/dL) 117 (31.6) 110 (26.9) 0.37
Apolipoprotein B (mg/dL) 113 (20.7) 106 (16.9) 0.14
Apolipoprotein A-I (mg/dL) 120 (15.3) 123 (18.6) 0.46
Glucose (mg/dL) 99.7 (8.88) 102 (9.67) 0.44
∆ Non-HDLc
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 164 (29.9) 165 (32.6) 1.66 (22.7) p=0.683
Moderate Fat 148 (30.2)156 (27.9) 7.97 (25.7) p=0.095
(MF vs. LF)
-6.31 [6.11] [-18.5, 5.91]
p=0.306
∆ Total cholesterol
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 203 (32.2)207 (32.4)
4.16 (20.8) p=0.268
Moderate Fat 184 (31.3)198 (29.3)
8.90 (26.3) p=0.069
P value (MF vs. LF)
-4.75 [5.97] [-16.7,7.19]
p=0.430
∆ Triglycerides
Baseline
Mean (SD)
End of extension
period
Mean (SD)
[median for
skewed items]
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 234 (67.8)264 (186) [218]
30.1 (170) p=0.324
Moderate Fat 190 (83.8)215 (103) [192]
25.6 (104) p=0.179
P value (MF vs. LF)
4.45 [35.5] [-66.6,75.5]
p=0.901
∆ LDLc
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 117 (31.6)113 (36.4)
-4.28 (22.0) p=0.279
Moderate Fat 110 (26.9)113 (28.8)
2.90 (26.1) p=0.541
P value (MF vs. LF)
-7.18 [6.08] [-19.3,4.96]
p=0.242
∆ HDLc
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 38.9 (6.86)41.4 (9.46)
2.50 (5.92) p=0.023
Moderate Fat 40.7 (8.27)41.6 (7.77)
0.935 (5.38) p=0.341
P value (MF vs. LF)
1.56 [1.43] [-1.29,4.42]
p=0.277
∆ Apo-B
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat 113 (20.7) 114 (18.8)-0.0978 (14.1)
p=0.970
Moderate Fat106 (16.9) 109 (19.7)
2.73 (13.3) p=0.270
P value (MF vs. LF) -2.83 [3.51] [-9.86,4.20]
p=0.423
∆ Apo-A1
Baseline
Mean (SD)
End of extension
period
Mean (SD)
Change during
study period
Mean (SD)
Difference between
diets
Mean (SE) [95% CI]
Low Fat120 (15.3) 134 (14.9) 13.8 (12.1) p<0.001
Moderate Fat123 (18.6) 131 (16.8)
7.70 (12.3) p=0.002
P value (MF vs. LF) 6.07 [3.12] [-0.178,12.3]
p=0.057
Adherence
% calories from
carbohydrate
Mean (SD)[rec]
% calories from protein
Mean (SD)[rec]
% calories from fat
Mean (SD)[rec]
Low Fat53.87 (9.60)
[65]19.91 (5.55)
[15]25.96 (8.50)
[20]
Moderate Fat47.45 (9.92)
[45]17.50 (5.37)
[15]34.58 (8.30)
[40]
Conclusions
First study looking at lipid outcomes in MetS patients at weight stability, under truly free-living conditions
Significantly lower drop out rate compared to prior studies
Able to sustain the benefits noted during controlled feeding phase, even under free-living conditions
No significant difference between the two diets in lipid outcomes likely related to not achieving carbohydrate and fat goals in 2 diets
Acknowledgements
DMetS participants
Northwest Lipid Research Clinic Staff
University of Washington CRC Staff
Alice Dowdy and Brian Fish
Dr. Robert H. Knopp, original PI for DMetS, who passed away on 5/30/10
Dr. Pathmaja Paramsothy, PI and phenomenal mentor!
Thank you