Two-year follow-up after gastric bypass surgery : sustained beneficial effect on metabolic health and hormonal dynamics in subjects with type 2 diabetes

• Background and aims: Gastric bypass surgery (GBP) not only reduces weight but improves glycaemic control in type 2 diabetes (T2DM) patients as well. To explore the mechanisms behind this, we studied the metabolic effects of GBP over time using an integrative approach.Materials and methods: We conducted a prospective study of 13 subjects with T2DM since 4 ±3 years, treated with oral glucose lowering drugs (GLD), recruited before their GBP surgery (3M/ 10F, age 51 ± 9 years). Subjects were assessed at preoperative baseline (BL) and four weeks (4W), six months (6M) and two years (2Y) post-operatively. During visits, fasting hormone and metabolite levels were measured, as well as resting heart rate variability (HRV) followed by subcutaneous adipose tissue (AT) biopsies, a 30 min 5 gram IV-arginine challenge (ARG) and a 180 min oral glucose tolerance test (OGTT).Results: All but one subject discontinued their GLD after surgery and remained without antidiabetic drugs at 2Y follow-up. HbA1c was reduced after surgery and remained at non-diabetic levels at 2Y (see Table. SD=standard deviation. SEM=standard error of the mean. P-value from Student’s T-test). Fasting insulin was reduced significantly 4W after surgery (28.0 ±10.8 mE/L vs 14.4 ±10.8 mE/L) and even lower at 6M (8.9 ±5.6 mE/L) and 2Y (8.0 ±6.2 mE/L). Fasting cortisol was significantly lower than BL at 4W, but significantly increased relative to BL levels at 6M. ACTH was lower than BL at 4W and 6M (borderline significant), but returned to BL levels at 2Y. Insulin excursions after arginine stimulation were markedly reduced 4W after surgery and remained so at 6M and 2Y (data not shown). At all time points after surgery, peak p-glucose during OGTT occurred earlier, as did the consequent drop in glucose levels. The secretion of insulin during OGTT mirrored this pattern. Total GLP-1 levels during OGTT (area under the curve=AUC) increased significantly 4W after surgery and remained increased at 6M and 2Y. AUC for GIP during OGTT had decreased significantly 4W after surgery and continued to do so for 6M and 2Y. Both GLP-1 and GIP however showed an earlier peak in secretion. HOMA-IR improved after surgery (see Table) and remained so at 2Y. Total body fat decreased with GBP (Table), as did adipocyte cell size vs BL (diameter 110.7±11.2 μm) at 4W (94.9±13.1 μm, p=0.013), 6M (101.6±13.1 μm, p=0.0035) and 2Y (93.1±12.7 μm, p<0.001).Conclusion: GBP improves glucose control in T2DM and reduces the need for GLD. Beneficially effects on metabolic parameters and adipocyte morphology are still seen after 2Y of follow-up. A marked increase in AUC for GLP-1 whereas AUC for GIP decreases after surgery, although both have an earlier peak in secretion during OGTT. A decrease in morning cortisol is seen at 4W after GBP, but no concomitant rise in ACTH, suggesting a central mechanism might affect cortisol and in turn contribute to early improvements in glucose homeostasis.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

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