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Differential trajectories in altered insulin sensitivityfollowing weight loss and their impact on circulatoryamino acids: Results from the PREVIEW: New Zealandsub-study
Utpal K. Prodhan1, Amber M. Milan1, Marta P. Silvestre2, Pia Christensen3, Anne Raben3, Mikael Fogelholm4, Sally D. Poppitt2, David Cameron-Smith1
1 Liggins Institute, The University of Auckland, Auckland, New Zealand.2 Human Nutrition Unit, School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
3 Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
4 Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
https://www.theguardian.com/world/2016/jun/27/disney-depiction-of-obese-polynesian-god-in-film-moana-sparks-anger. Photograph: YouTube/Disney
Prevalence of Overweight & Obesity in New Zealand in 2017 : 1/3, 1/3, 1/3
3732
30
0
5
10
15
20
25
30
35
40
Men & Women; All ethnicities
% o
f po
pula
tion
Overweight Obese Lean
3rd in the OECD
OECD obesity update_2017
Obesity with T2DM
Nutrient excess
Normal Insulin-resistant obesity
Nutrient excess
Diet, IR & T2DM: Relation to BCAA
Pancreas
Pancreatic cell failure to produce sufficient insulin
Fasting Plasma BCAA Raand/or Rd Hyperglycemia
Muscle
mTORC1 activation?S6K1 activation
pS-IRS-1pS-IRS-2
Insulin resistance
Plasma BCAAInsulin levels
High protein diet
C. J. Lynch and S. H. Adams, Nat. Rev. Endocrinol., 2014, 10, 723–36
Leucine
Rationale and Hypothesis
We hypothesized that-
Dietary energy restricted weight loss would-• Reduce circulatory AA profile, including BCAA• Changes in AA will correlate to the improvement in
insulin sensitivity
Anne Raben
Thomas Larsen
Mikael Folghelhom
Ian McDonald
Margriet Westerterp
Alfredo Martinez
Sally Poppitt
Jennie Brand-Miller
FinlandDenmark
UK
Netherlands
Spain
AUS
NZ
Bulgaria
PREVIEW: NZ (Prevention of Diabetes through Lifestyle Intervention in Europe and around the World)
PREVIEW: NZ
Weight loss with LED
Recruiting criteria Prediabetic (ADA criteria)
• IFG: Fasting glucose 5.6–6.9 mmol/L; and/or
• IGT: fasting glucose <7.0 mmol/L, and 7.8–11.0 mmol/L at 2 h after 75 g glucose
• Low Energy Diet (LED)• 3.4 MJ/day• 15-20 E% Fat
• 35-40 E% Protein (84 g)• 45-50 E% Carbohydrate
Target: To lose >8% initial body weight
The LED was provided by the Cambridge Weight Plan Ltd., UK
LED
Body composition measured with DXA Serum amino acids measured with UPLC
Examination conducted
ResultsWeight loss improved body composition
n=168; Data presented as Mean ± SD *** Differences are significant (p <0.05)
Weight loss improved Insulin Sensitivity
n=168; Data presented as Mean ± SD *** Differences are significant (p <0.05)
NEAA
Weight loss altered amino acid concentrations
Data presented as a fold change compared to the baseline values (week 0) *Differences are significant (p <0.05)
Non-proteogenic
AA EAA
Relationship between BCAA and Insulin Sensitivity
Relationship between BCAA and Insulin Sensitivity
Data presented as Mean ± SD
Conclusions
BCAA positively correlated with IR at week-0 and week-8Though the insulin sensitivity improved with weight loss,
change in BCAA was not associated with this change
Acknowledgements• Prof David Cameron-Smith• Prof Sally Poppitt• Dr. Marta P. Silvestre• Dr. Amber Milan• Pia Christensen• Anne Raben• Mikael Fogelholm• PREVIEW Team