1. Determinants of response/non-response to dietary
fat interventions on biomarkers of insulin resistance
I de Stanlaigh, A.M Murphy, Prof.HM Roche
Nutrigenomics Research Group, UCD Conway Institute for Biomolecular and Biomedical Sciences / UCD Institute of Food and Health,
School of Public Health, Physiotherapy and Sports Science, University College Dublin, Belfield, Dublin 4.
 Observational studies have indicated associations between dietary fat intake
and the development of insulin resistance.
 Intervention studies however, have concluded mixed results and
demonstrated variability in cohort response.
 This variability allows for investigation into phenotypes more responsive to
dietary fat interventions ➔ more personalised and effective treatments
1) Heterogeneity in HOMA-IR response to the
LIPGENE intervention
Figure 1. Change in HOMA-IR in LIPGENE cohort
(n=400) regardless of diet group.
Change in HOMA-IR
2) Similar patterns of HOMA-IR response evident across
the diet groups
Figure 2 Change in HOMA-IR in 4 diet groups: HSFA, High fat SFA;HMUFA, High fat
MUFA;LFHCC, low fat high complex CHO;LFHCC n-3 PUFA, LFHCC and n-3 PUFA
supplement
Introduction
Aim: To investigate the metabolic and inflammatory
phenotypes that determine response/non-response to
dietary fat interventions.
• Change in insulin sensitivity post intervention
was dictated by more than dietary fat
modification.
• C-peptide and fasting insulin levels pre-
intervention influenced response to intervention
⇰Higher levels in Responders IR➞IS may indicate
increased potential to normalise.
⇰ This was also reflected in higher pre intervention
Insulin:C-peptide ratio, indicative of pancreatic
insulin secretion capacity.
Results
• Examined the effects
of changes in dietary
fat intake on insulin
sensitivity.
• Subjects with the
Metabolic Syndrome
N=417 randomly
assigned to 4 diet
groups
12 week dietary
intervention
SFA intake had no
effect on insulin
sensitivity overall.
However, Post hoc
analyses indicated
a level of response
in some subjects
Results
Defining response groups
Conclusion
• High fat SFA
• High fat MUFA
• Low fat, high
complex CHO
• Low fat, high
complex CHO + n-3
PUFA supplement
3) Groups defined as: Non responders,
Responders IS→IR, Responders IR→IS
Figure 3 Split of LIPGENE cohort with
available HOMA-IR data into 3 response
groups
Pre fasting insulin and pre and post C-peptide are strong
predictors of response (change in HOMA-IR) to intervention
Acknowledgements
Nutrigenomics Research Group at the Conway Institute UCD; in particular, Prof. Helen Roche and Aoife Murphy for their guidance and support.
LIPGENE investigators and participants. LIPGENE was funded by the EU 6 Framework Food Safety &Quality Programme, Contract no. 505944, ‘Diet, genomics,and the metabolic
syndrome: an integrated nutrition, agrofood,social and economic analysis.’ Funds were also obtained from the Norwegian Foundation for Health and Rehabilitation, South-Eastern
Norway Regional Health Authority, the Johan Throne Holst Foundation for Nutrition Research and the Freia Medical Research Foundation.
HSFA HMUFA
LFHCC LFHCC n-3 PUFA
Independent Predictors (pre and post phenotypic) of HOMA- IR response to dietary fat
intervention in the LIPGENE cohort (n=400)
R2=0.550, P=0.001
Predictor Standardised Beta
coeffecient
P-value
Pre fasting insulin (mmol l-1) -0.679 0.001
Post C-Peptide (ngml) 0.951 0.001
Pre C-Peptide (ngml) -0.315 0.001
Pre fasting glucose (mmol l-1) -0.131 0.001
Post NEFA -0.080 0.001
P<0.05 considered statistically significant as assessed by stepwise multiple regression
analysis.
Non Responders
(n=134)
Responders IR➞IS
(n=153)
Responders IS➞IR
(n=113)
Diet Group (A:B:C:D) 34:42:32:26 34:41:41:37 28:27:31:27
Male female (n:n) 60:74 61:92 54:59
Mean s.e.m Mean s.e.m Mean s.e.m P value
Age 54.94 0.772 55.00 0.710 54.73 0.892 0.933
BMI (kg/m2) 30.99 0.351 32.62 0.332 33.42 0.411 0.001
Body weight (Kg) 87.92 1.212 90.77 1.10 95.06 1.348 0.001
Waist Circumference (cm) 103.41 1.033 106.31 0.776 108.82 1.000 0.001
Waist: Hip (cm) 0.94 0.009 0.95 0.006 0.95 0.008 0.264
BMR 7.04 0.098 7.08 0.088 7.32 0.113 0.089
HOMA-IR 2.11 0.092 3.32 0.132 2.50 0.156 0.001
Figure 4. Abbreviations: Diet A,High fat SFA; B, High fat MUFA; C, Low fat high complex CHO; D, LFHCC n-3 PUFA;
BMR, basal metabolic rate. Values represent means and s.e.m. P<0.05 (Kruskall Wallis H test).
Baseline characteristics of subjects, grouped according to response to dietary fat
modification based on change in HOMA-IR.
BMI, body weight and waist circumference were included in the model
but were not determinants of response.
LIPGENE subjects
with HOMA-IR data
N=400
Non Responders
0.4>Change in HOMA-
IR>-0.4
N=134
Responders IS→IR
Change in HOMA-IR >
0.4
N=113
Responders IR→IS
Change in HOMA-IR <
-0.4
N= 153
Outliers
N=7
Non Responders
(n=134)
Responders IR➞IS
(n=153)
Responders IS➞IR
(n=113)
Diet Group (A:B:C:D) 34:42:32:26 34:41:41:37 28:27:31:27
Male female (n:n) 60:74 61:92 54:59
Mean s.e.m Mean s.e.m Mean s.e.m P value
Pre Fasting Insulin
(mmol l-1
)
8.03 0.334 12.16 0.439 9.44 0.521 0.001
Pre Fasting Glucose
(mmol l-1) 5.86
0.067 6.09 0.068 5.89 0.077 0.001
Pre C-Peptide (ngml) 2.33 0.072 2.84 0.070 2.67 0.085 0.001
Pre Fasting Insulin : C-
Peptide
3.44 0.107 4.34 0.132 3.50 0.154 0.001
Post Fasting Insulin: C-
Peptide
3.13 0.010 3.12 0.092 3.95 0.110 0.001
C-Peptide and fasting insulin pre intervention were
significantly higher in Responders IR➞IS
Figure 6. Values represent means and s.e.m. P<0.05 considered statistically significant as
assessed by Kruskall Wallis H test
Figure 7. Pre C-Peptide and Pre fasting insulin: C-peptide
ratio in the three response groups