Key result
Roux-en-Y gastric bypass lowers HbA1c by ~14 mmol/mol in patients with type 2 diabetes.
Why the study?
Roux-en-Y gastric bypass markedly improves glycemia in type 2 diabetes, but the underlying mechanisms and changes over time remain incompletely understood.
Does Roux-en-Y gastric bypass surgery improve metabolic, neuroendocrine, and adipose profiles over 2 years in patients with obesity and type 2 diabetes?
RCT (n=35)
randomized
No
Does Roux-en-Y gastric bypass surgery improve metabolic, neuroendocrine, and adipose profiles over 2 years in patients with obesity and type 2 diabetes?
Absolute Event Rate: 41% vs 55%
p-value: p=< 0.001
Roux-en-Y gastric bypass induces rapid glycemic improvement potentially mediated by early neuroendocrine changes, followed by long-term improvements in adipose tissue insulin sensitivity and weight loss.
RYGB may sustain glycemic control in obese T2D via phased mechanisms; extends mechanistic insights but leaves open causality and generalizability.
CONTEXT: 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. OBJECTIVE: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB. DESIGN AND SETTING: Follow-up of single-center randomized study. PATIENTS: Thirteen patients with obesity and T2D compared to 22 healthy subjects. INTERVENTIONS: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB. RESULTS: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (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). CONCLUSIONS: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (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.
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Almby et al. (2021) conducted an RCT in Type 2 diabetes and obesity (n=35). Roux-en-Y gastric bypass surgery (RYGB) vs. Baseline / healthy subjects was evaluated on Hemoglobin A1c (p=< 0.001). Roux-en-Y gastric bypass surgery in patients with type 2 diabetes reduced hemoglobin A1c from a mean of 55 to 41 mmol/mol by 104 weeks (P < 0.001).
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