Clinical Insulin Resistance Group

Research at the Clinical Insulin Resistance Group is focused on uncovering the molecular pathways involved in the transition from health to insulin resistance and metabolic disease related to overweight and obesity in humans. In our clinical studies, we use gold-standard protocols to deeply phenotype individuals at risk of type 2 diabetes. Using gold-standard tools to characterise whole-body glucose regulation, abdominal fat distribution and liver fat, we find a wide range of phenotypic variation in obesity and prediabetes. Current projects: 1. The effect of weight cycling on insulin resistance and fatty liver in human 2. Metabolomic and lipidomic screens of liver and muscle insulin resistance in human obesity uncovering bio-markers to predict response to the first-line medication in type 2 diabetes, metformin (in collaboration with Dr O'Sullivan, Dr Koay and Dr Yang, The University of Sydney) 3. A randomised clinical trial (https://clinicaltrials.gov/ct2/show/NCT03558867) to test the efficacy of an algorithm-based (personalised) diet in combination with metformin on glycaemia in individuals with prediabetes and type 2 diabetes (in collaboration with Prof Elinav and Prof Segal, The Weizmann Institute of Science). 4. Reverse engineering insulin secretion in health and disease (in collaboration with Dr Danny Ben-Zvi, The Hebrew University of Jerusalem) - Masters project available in clinical study settings (July 2019)

Harari A, Coster ACF, Jenkins A, Xu A, Greenfield JR, Harats D, Shaish A, Samocha-Bonet D. Obesity and insulin resistance are inversely associated with serum and adipose tissue carotenoid concentrations in adults. J Nutr 2019 (Accepted July 2019)

Tang A, Coster ACF, Tonks KT, Heilbronn LK, Pocock N, Purtell L, Govendir M, Blythe J, Zhang J, Xu A, Chisholm DJ, Johnson NA, Greenfield JR and Samocha-Bonet D. Longitudinal changes in insulin resistance in normal weight, overweight and obese individuals. J Clin Med 2019 May 8;8(5). pii: E623. doi: 10.3390/jcm8050623

Samocha-Bonet D, Debs S, Greenfield JR. Prevention and Treatment of Type 2 Diabetes – A Pathophysiological-Based Approach. Trends Endocrinol Meta 2018; 29(6): 370-379 doi: 10.1016/j.tem.2018.03.014

 Kozan P, Blythe J, Greenfield J, Samocha-Bonet D. The Effect of Buffering High Acid Load Meal with Sodium Bicarbonate on Postprandial Glucose Metabolism in Humans—A Randomized Placebo-Controlled Study. Nutrients 2017; 9(8): 861.

 Chen DL, Brown R, Liess C, Poljak A, Xu A, Zhang J, Trenell M, Jenkins A, Chisholm D, Samocha-Bonet D, Macefield VG, Greenfield JR. Muscle sympathetic nerve activity is associated with liver insulin sensitivity in obese non-diabetic men. Front Endocrinol 2017; 8: 101.

Tonks KT, White CP, Centre JR, Samocha-Bonet D, Greenfield JR. Bone turnover is suppressed in insulin resistance, independent of adiposity. J Clin Endocrinol Metab 2017 102 (4) 1112-1121.

Tam CS, Chaudhuri R, Hutchison AT, Samocha-Bonet D, Heilbronn LK. Skeletal muscle extracellular matrix remodelling after short-term overfeeding in healthy humans. Metabolism 2017 Feb; 67:26-30.  

MacKie GM, Samocha-Bonet D, Tam C.  Does weight cycling promote obesity and metabolic disease? Obesity Research & Clinical Practice 2017 11(2) 131-139 Review.

Tonks KT, Coster ACF, Christopher MJ, Chaudhuri R, Xu A, Gagnon-Bartsch J, Chisholm DJ, James DE, Meikle PJ, Greenfield JR, Samocha-Bonet D. Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans. Obesity 2016. 24(4):908-16.

Chen DL, Liess C, Poljak A, Xu A, Zhang J, Thoma C, Trenell M, Milner B, Jenkins AB, Chisholm DJ, *Samocha-Bonet D, *Greenfield JR Phenotypic characterization of insulin-resistant and insulin-sensitive obesity. J Clin Endocrinol Metab 2015 100(11):4082-91. 

Williams RS, Kozan P, Samocha-Bonet D The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans. Biochimie 2016 S124: 171-7  

Williams RS, Heilbronn LK, Chen DL, Coster AC, Greenfield JR, Samocha-Bonet D Dietary acid load, metabolic acidosis and insulin resistance - lessons from cross-sectional and overfeeding studies in humans. Clin Nutr Aug 12. pii: S0261-5614(15)00218-6. doi: 10.1016/j.clnu.2015.08.002. 

Samocha-Bonet D, Chisholm DJ, Holst JJ, Greenfield JR  L-glutamine and whole protein restore first-phase insulin response and increase glucagon-like peptide-1 in type 2 diabetes patients  Nutrients 2015 7(4):2101-8

Samocha-Bonet D, Chisholm DJ, Gribble FM, Coster AC, Carpenter KH, Jones GR, Holst JJ, Greenfield JR Glycemic Effects and Safety of L-Glutamine Supplementation with or without Sitagliptin in Type 2 Diabetes Patients-A Randomized Study PLoS One 2014 9(11):e113366. 

Samocha-Bonet D, Dixit VD, Kahn CR, Leibel RL, Lin X, Nieuwdorp M, Pietiläinen KH, Rabasa-Lhoret R, Roden M, Scherer PE, Klein S, Ravussin E. Metabolically healthy and unhealthy obese - the 2013 Stock Conference report. Obes Rev 2014 15(9):697-708.

Samocha-Bonet D, Tam CS, Campbell LV, Heilbronn LK. Raised circulating fetuin-A after 28-day overfeeding in healthy humans Diabetes Care 2014 37:e15-16 

Heilbronn LK, Campbell LV, Xu A, Samocha-Bonet D Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans. PLoS One 2013 8:e78864

Heilbronn LK, Coster ACF, Campbell LV, Greenfield JR, Lange K, Christopher MJ, Meikle PJ, Samocha-Bonet D. The effect of short term overfeeding on serum lipids in healthy humans. Obesity 2013 21:E649-659 

Hocking S, Samocha-Bonet D, Milner K-L, Greenfield JR, Chisholm DJ. Adiposity and Insulin Resistance in Humans: The Role of the Different Tissue and Cellular Lipid Depots. Endo Rev 2013; 34:463-500.

Samocha-Bonet D, Chisholm DJ, Tonks K, Campbell LV, Greenfield JR. Insulin-sensitive obesity in humans - a 'favorable fat' phenotype? Trends Endocrinol Metab 2012; 23:116-124.

Samocha-Bonet D, Campbell LV, Mori TA, Croft KD, Greenfield JR, Turner N, Heilbronn LK. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans. PLoS One 2012; 7:e36320.

Tam CS, Viardot A, Clement K, Tordjman J, Tonks K, Greenfield JR, Campbell LV, Samocha-Bonet D, Heilbronn LK. Short-term overfeeding may induce peripheral insulin resistance without altering subcutaneous adipose tissue macrophages in humans. Diabetes 2010; 59:2164-2170.

Samocha-Bonet D, Heilbronn LK, Lichtenberg D, Campbell LV. Does skeletal muscle oxidative stress initiate insulin resistance in genetically predisposed individuals? Trends Endocrinol Metab 2010; 21(2):83-87.

Samocha-Bonet D, Campbell LV, Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK. A family history of type 2 diabetes increases risk factors associated with overfeeding. Diabetologia 2010; 53:1700-1708.