The twin cycle hypothesis Substantial weight loss in people with - PowerPoint PPT Presentation

The twin cycle hypothesis Substantial weight loss in people with type 2 diabetes will: Pancreas Liver Decrease fat – Decrease fat – normalise the insulin improve insulin action and response to eating and normalise overnight blood sugar

The Counterpoint study – Type 2 diabetes, 800kcal diet 10 Fasting glucose (mmol/l) 8 6 4 0 2 4 6 8 Week 20 15 Insulin sensitivity Liver 15 10 Fat % Index 10 5 5 0 0 0 2 4 6 8 0 2 4 6 8 a 0.8 12 insulin secretion First phase 0.6 Pancreas 9 Fat % 0.4 6 0.2 3 0.0 0 2 4 6 8 0 2 4 6 8 Week Week

Reversibility of type 2 diabetes 100 % Insulin suppression 80 of HGP 60 40 The pathophysiological 20 defects in the liver and 0 Week 0 Week 1 Week 4 Week 8 pancreas are reversible – First phase insulin response 1.0 if diabetes duration <4yr 0.8 (nmol/min/m 2 ) 0.6 0.4 0.2 0.0 0 2 4 6 8 0 1 4 8 Can long duration type 2 diabetes also be reversed?

The Counterbalance Study – Counteracting BetA cell failure by Long term Action to Normalize Calorie intakE Questions: Can people with longer duration type 2 diabetes reverse to normal? Is the reversal of type 2 diabetes durable if body weight remains stable?

Protocol for CounterBalance study Stepped return to normal eating T2DM < 4 yr Very low calorie diet Weight maintenance T2DM > 8 yr 8 10 0 1 4 8 10 + 6 months Weeks

Counterbalance Subjects Diabetes duration 0-4y 8-23y (n=15) (n=14) Age (yr) 52.1 ± 2.6 61.6 ± 2.0 Weight (kg) 99.0 ± 3.7 96.9 ± 3.8 BMI (kg/m 2 ) 34.6 (27.6-38.0) 33.0 (29.4-45.7) FPG (mmol/l) 9.6 ± 0.7 13.4 ± 0.8 HbA1c (mmol/mol) 55 ± 2 70 ± 4 Fasting insulin 17.4 (3.9-48.9) 7.0 (4.1-31.9) Steven et al Diabetic Med 2015

Results: weight loss during diet Weight loss: 14.6 ± 0.8 % vs. 14.5 ± 0.7 % p=0.662

Fasting plasma glucose during diet Steven et al Diabetic Med 2015

By diabetes duration <4 y 8-12 y >12 y 5.8 mM 6.2 mM 10.6 mM Spearman 0.501; p=0.006 Steven et al Diabetic Med 2015