CALIBER Phase 1: A Pilot Study in Normal-weight and Overweight Adults. (CALIBER)

CALIBER (Carbohydrates, Lipids and Biomarkers of Traditional and Emerging Cardiometabolic Risk Factors) Phase 1: A Pilot Study in Normal-weight and Overweight Adults.

Pilot study to compare the impact of following a low-carbohydrate, high-fat diet versus following a high-carbohydrates, moderate-fat diet (UK dietary guidelines) on cardiometabolic risk markers and associated behaviours in a normal-weight and overweight adult population.

Cardiometabolic diseases (CMD), such as type 2 diabetes and cardiovascular disease (CVD), are globally amongst the highest contributors to morbidity and mortality with high (cost) implications to the overall economy and health care systems. A number of risk markers have been associated with CMDs, including blood serum markers, low levels of lean mass and high levels of body fat, including increased waist circumference. Dietary factors and nutritional status have long been linked with specific markers of cardiometabolic (CM) risk. The quantity and quality of dietary carbohydrates has been associated with increased serum triglycerides levels, increased body fat mass, increased waist circumference and visceral fat around the organs in particular. They also seem to increase food cravings. Whilst official dietary guidelines in the UK and elsewhere still recommend a high carbohydrate and low fat diet as standard, these recommendations have increasingly been challenged. Evidence has been mounting that very-low carbohydrate (ketogenic) and low carbohydrate diets can ameliorate CM risk factors, especially when a personalised rather than a one-size-fits-all approach is being taken. Response to carbohydrate load and adherence to dietary interventions can vary widely dependent on individual substrate and energy metabolism and insulin-resistant status. The majority of dietary interventions with ketogenic and low-carbohydrate diets has focused on weight loss as the primary outcome in overweight and obese individuals. However, in recent years evidence has been mounting that the location and quality of adipose tissue (AT) play a more important role in manifestation of CM risk than quantity of AT alone. Detrimental health behaviours, such as low-quality diet and low levels of physical activity seem to be important contributors to this. Further studies can provide vital insights into the links between diet, location-specific adipose tissue, CM risk factors and health-related behaviours. Therefore this 8-weeks randomised pilot study will investigate the impact of either following a low-carbohydrate, high-fat diet versus following a high-carbohydrates, moderate-fat diet (UK dietary guidelines) on cardiometabolic risk markers and associated behaviours in a normal-weight and overweight adult population aged 19 - 64 at potential risk of CMD.

Due to the nature of the low-carbohydrate, high-fat and high-carbohydrate, moderate-fat diets masking is not feasible.

Total cholesterol, HDL-C, LDL-C, non-HDL cholesterol, small-dense LDL-C and triglycerides measured in mmol/L

Inclusion Criteria cohort 1: BMI 18.5 - 29.9kg/m2 Aged 19 - 64 White-Caucasian Score of ≥4 from a combination of risk markers, including Fasting glucose concentration >5.5mmol/L = 3 points Waist >102cm or 40 inches = 2 points (males) Waist >94 cm or 37 inches = 1 point (males) Waist >88cm or 34inches = 2 points (females) Waist >80 cm or 31 inches = 1 point (females) Systolic blood pressure>130mmHg = 1 point Diastolic BP >85mmHg = 1 point HDL cholesterol concentration <1.0mmol/L = 2 points Serum triglyceride concentration >1.3mmol/L = 1 point. Exclusion Criteria cohort 1: Smoker Vegetarian or vegan Suffering from food allergies or intolerances Drinking alcohol above recommended UK government guidelines Previous diagnosis of CM disease Taking lipid-lowering medication Taking blood pressure-lowering medication Taking blood glucose-lowering medication Taking dietary supplements Suffering from an eating disorder Current or previous renal impairment Inclusion Criteria cohort 2: BMI 18.5 - 29.9kg/m2 Aged 19 - 64 White-Caucasian Exclusion Criteria cohort 2: Smoker Vegetarian or vegan Suffering from food allergies or intolerances Drinking alcohol above recommended UK government guidelines Previous diagnosis of CM disease Taking lipid-lowering medication Taking blood pressure-lowering medication Taking blood glucose-lowering medication Taking dietary supplements Suffering from an eating disorder Current or previous renal impairment

Brehm, B. et al. (2003) A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women J Clin Endocrinol Metab 88(4), 1617

Buyken, A., Goletzke, J., Joslowski, G., Felbick, A., Cheng, G., Herder, C. and Brand-Miller, J. (2014) Association between carbohydrate quality and inflammatory markers: systematic review of observational and interventional studies Am J Clin Nutr 99(4),

De Larochellière, E. et al. (2014) Visceral/epicardial adiposity in nonobese and apparently healthy young adults: association with the cardiometabolic profile Ath

Fischer, K., Pick, J., Moewes, D. and Nöthlings, U. (2015) Qualitative aspects of diet affecting visceral and subcutaneous abdominal adipose tissue: a systematic review of observational and controlled intervention studies Nutr Rev 73(4), 191-215

Gadgil, M., Appel, L., Yeung, E., Anderson, C., Sacks, F. and Miller, E. (2013) The effects of carbohydrate, unsaturated fat, and protein intake on measures of insulin sensitivity: results from the OmniHeart trial Diabetes Care 36 (5), 1132-1137

Hu, T. and Bazzano, L. (2014) The low-carbohydrate diet and cardiovascular risk factors: evidence from epidemiologic studies Nutr Metab Cardiovasc Dis 24(4), 337-343

Hu, T., Yao, L., Reynolds, K., Niu, T., Li, S., Whelton, P., He, J., Steffen, L. and Bazzano, L. (2016) Adherence to low-carbohydrate and low-fat diets in relation to weight loss and cardiovascular risk factors Obes Sci Pract, 2(1), 24-3

Ko, B., Park, K., Shin, S., Zaichenko, L., Davis, C., Crowell, J., Joung, H. and Mantzoros, C (2016) Diet quality and diet patterns in relation to circulating cardiometabolic biomarkers Clin Nutr. 35(2), 484-90

Lee, M., Wu, Y. and Fried, S. (2013) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications Mol Aspects Med 34 (1), 1-11

Lennerz, B., Alsop, D., Holsen, L., Stern, E., Rojas, R., Ebbeling, C., Goldstein, J.and Ludwig, D. (2013) Effects of dietary glycemic index on brain regions related to reward and craving in men Am J Clin Nutr 98(3), 641-647

Allam-Ndoul, B., Guénard, F., Garneau, V., Cormier, H., Barbier, O., Pérusse, L., et al. (2016) Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status. Nutrients 8(6)

Lin, Z., Gong, Q., Wu, C., Yu, J., Lu, T., Pan, X., Lin, S. and Li, X. (2012) 'Dynamic change of serum FGF21 levels in response to glucose challenge in human J Clin Endocrinol Metab, 97(7), E1224-1228.