Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D) but underlying mechanisms and changes over time are incompletely understood.Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB.Follow-up of single-center randomized study.Thirteen patients with obesity and T2D compared to 22 healthy subjects.Blood chemistry, adipose biopsies and heart rate variability were obtained before and 4, 24 and 104 weeks post-RYGB.After RYGB, glucose-lowering drugs were discontinued and HbA1c fell from mean 55 to 41 mmol/mol by 104 weeks (p<0.001). At 4 weeks, morning cortisol (p<0.05) and ACTH (p=0.09) were reduced by 20%. Parasympathetic nerve activity (HRV-derived) increased at 4 weeks (p<0.05) and peaked at 24 weeks (p<0.01). CRP and white blood cells were rapidly reduced (p<0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation and adipogenesis was upregulated (p<0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (p<0.01).We propose this order of events: 1) rapid glucose lowering (days). 2) attenuated cortisol axis activity and inflammation, increased parasympathetic tone (weeks). 3) Body fat and weight loss, increased adipose glucose uptake and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.
Kristina E Almby, Petros Katsogiannos, Maria J Pereira, F Anders Karlsson, Magnus Sundbom, Urban Wiklund, Prasad G Kamble, Jan W Eriksson