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