Hippocrates Prize Prof A. Kokkinos (Greece)

15th Meeting of the Mediterranean Group for the Study of Diabetes Comparison of Roux-en-Y gastric bypass and sleeve gastrectomy in the improvement of insulin sensitivity Kokkinos A1, Liaskos C1, Liatis S1, Tentolouris N1, Alexiadou K1, Perrea D1, Diamantis T2, Katsilambros N1 1First Department of Propaedeutic Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 2First Department of Surgery, Medical School, National and Kapodistrian University of Athens, Athens, Greece 15th Meeting of the Mediterranean Group for the Study of Diabetes Athens, 27-29 April, 2017

INTRODUCTION ● Bariatric surgery: the most effective method for the long-term treatment of morbid obesity Sjöström L et al, N Engl J Med 2007;357:741-752

THE SOS STUDY ● Reduction in mortality by 30% ● Important reduction in incidence and increase in recovery rate for all cardiovascular risk factors ● Impressive beneficial effects on T2DM Sjöström L, Int J Obes (Lond) 2008;32:S93-S97

● 150 overweight and obese T2DM patients randomized to: - Intensive medical therapy - Roux-en-Y gastric bypass (RYBG) or sleeve gastrectomy (SG) ● Primary endpoint: HbA1c ≤6% with or without medication Schauer P et al, N Engl J Med 2017;376:641-651

Schauer P et al, N Engl J Med 2017;376:641-651

INTRODUCTION ● Glycemia improvement a result of: - Increase in insulin sensitivity (weight loss) - Specific effects associated with distinct surgical modalities (incretin response)

STUDY AIM To compare the effect of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on weight loss, insulin sensitivity, and postprandial glycemia and insulinemia

METHODS ● 12 morbidly obese patients undergoing RYGB, 15 undergoing SG ● No known T2DM, diabetes medications ● Matched for age and BMI ● Examined preoperatively, and at 3 and 6 months

METHODS (2) ● Test meal (200 ml ice-cream, 450 kcal) ● Blood samples at times 0’ and every 30 min until 180’ postprandially ● Glucose, insulin, HOMA-IR ● Area under the curve (AUC) for the postprandial response

Baseline characteristics RESULTS Baseline characteristics RYGB SG P Gender (♀/♂) 10/2 13/2 Age (years) 37.3 ± 8.1 40.7 ± 8.3 ns Weight (kg) 137.3 ± 18.8 135.0 ± 20.8 BMI (kg/m2) 48.7 ± 6.1 50.8 ± 7.2 Waist (cm) 127.8 ± 10.2 128.4 ± 14.8 Hip (cm) 141.0 ± 13.7 143.5 ± 13.8 WHR 0.93 ± 0.12 0.90 ± 0.11 Glucose (mg/dl) 95.8 ± 9.5 118.6 ± 38.5 Insulin (mU/l) 29.3 ± 21.5 26.2 ± 12.4 HOMA-IR 6.7 ± 5.6 8.4 ± 6.6

3 months RYGB SG P 6 months ΔBMI% -19.0 ± 3.9 -17.8 ± 5.1 ns -27.2 ± 4.6 -25.9 ± 5.1 Δglucose AUC% -8.6 ± 12.3 -13.8 ± 20.8 -12.8 ± 12.9 -21.4 ± 17.4 Δinsulin AUC% -51.5 ± 13.2 -39.2 ± 28.3 -57.1 ± 18.1 -54.3 ± 18.3 ΔHOMA-IR% -53.1 ± 32.1 -62.1 ± 19.0 -60.2 ± 20.8 -64.6 ± 19.0

CONCLUSIONS ● Both RYGB and SG lead to substantial decreases in weight, postprandial glycemia, insulinemia and insulin resistance ● The main drive behind metabolic improvements seems to be weight loss per se, not differences between the two surgical modalities

Further directions ● More patients ● 12 months, 2 years ● Gut hormones (GLP-1, PYY, Ghrelin)

GUT PEPTIDE RESPONSES AFTER RYGB ● 16 RYGB patients, test meal during the early postoperative period Le Roux CW et al, Ann Surg 2007;246:780-785

Alamuddin N et al, Obes Surg 2016;Dec 21 [e-pub ahead of print]