Effect of exogenous ketones in prediabetes: A randomised controlled - PowerPoint PPT Presentation

Effect of exogenous ketones in prediabetes: A randomised controlled trial Sakina H Bharmal PhD candidate

Sources of energy hvmn.com/ketone-ester/science

Metabolism of ketone bodies Newman, J. C., & Verdin, E. (2014). Trends in Endocrinology & Metabolism , 25 (1), 42-52

Ketosis hvmn.com/ketone-ester/science

Endogenous ketosis Ketogenic diet Pros  Aids in glucose allostasis, weight loss, and neurological conditions Cons  Increased levels of lipids  Long adaption period  Poor tolerance

Exogenous ketones hvmn.com/ketone-ester

Project goals To investigate the effect of exogenous ketones on metabolic markers (such as pancreatic hormones, incretins, lipids) in adults with prediabetes

C ross-over randomis E d T rial of β -hydroxyb U tyrate in prediabete S (CETUS)

Participants Exclusion criteria Inclusion criteria Individuals with diabetes 1) 1) Over 18 years On insulin treatment 2) Glycated haemoglobin 39-47 2) 3) On a ketogenic diet or consuming mmol/mol and/or fasting plasma nutritional ketone supplements glucose between 5.6-6.9 mmol/L Involved in extensive endurance 4) training or competitive athletics Pregnancy 5) Malignant tumours 6)

Baseline characteristics Characteristics Mean ± SD/ frequency Age (years) 55 ± 14 Sex Men 12 Women 6 BMI (kg/m 2 ) 28.4 ± 5.9 Waist circumference (cm) 98.6 ± 15.8 Hip circumference (cm) 106 ± 13 Systolic blood pressure (mmHg) 135 ± 27 Diastolic blood pressure (mmHg) 88.1 ± 12.8 39 ± 0.3 Glycated haemoglobin (mmol/L)

Clinical visit protocol Participants (n=18) No exercise No exercise No alcohol No alcohol Wash out period 7-10 days First clinical visit Second clinical visit Ketone ester supplement/ Baseline Ketone ester supplement/ Baseline Placebo Placebo Blood samples at 30 minutes Baseline bloods Blood samples at 30 minutes Baseline bloods interval up to 150 minutes interval up to 150 minutes

Study aims Primary aim: To investigate the effect of a single drink of ketone ester supplement on glucose levels in adults with prediabetes Secondary aim: To investigate its impact on pancreatic hormones and incretins

Statistical methods  Area under the curve for the primary (i.e., glucose) and secondary (i.e., pancreatic hormones and incretins) endpoints  Paired t tests and Cohen’s effect size were calculated to difference in means of the endpoints after ketone supplement versus placebo  Repeated measures ANOVA was conducted to determine the change in endpoints over time and to measure the interaction between the drinks and time

Ketone levels

Glucose levels

AUC of pancreatic hormones and incretins Hormones Placebo (n=18) KE βHB (n=18) p d Insulin (pmol/L) 28035 ± 6154 35189 ± 8732 0.02 0.61 C-peptide (nmol/L) 74 ± 8 100 ± 15 <0.01 0.89 Amylin (ng/L) 16859 ± 4203 17416 ± 4500 0.84 0.15 Glucagon (ng/L) 22994 ± 4890 22983 ± 4678 0.98 0.04 1479 ± 146 1965 ± 242 GIP (pmol/L) <0.01 0.77 GLP-1 (pmol/L) 9643 ± 968 9679 ± 899 0.91 0.02

Pancreatic hormones and incretins

Summary  A single drink of ketone supplement lowers glucose levels by 14.5% in prediabetes  A statistically significant interaction effect (drink x time) was observed for insulin, C-peptide, and GIP

Acknowledgements Food and Health Program seed funding (University of Auckland)