Early Changes in Glucose Homeostasis after Gastric Bypass Surgery in Patients with T2DM—Role of Adipose Tissue Mechanisms?

Abstract

Gastric bypass (GBP) surgery can effectively prevent or treat type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be important, but causality is not shown. We studied the relationship between early changes in whole-body and AT metabolism in obese T2D patients. Methods: Eight T2D patients with BMI 30-45 (M/F 3/5, age 49 ± 10) underwent GBP following 4 week low calorie diet. Assessments: OGTT, AT biopsies to measure gene expression in AT and in adipocytes size, glucose uptake (GU), lipolysis and insulin action. Results: At 4 and 24 weeks post-GBP, all subjects but one stopped diabetes medication. The Matsuda index increased compared to baseline, while HOMA-IR, fasting glucose, HbA1c and insulin levels decreased (p <0.01 for all). In adipocytes, basal, isoprenaline-stimulated or insulin-inhibited lipolysis rates and basal or insulin-stimulated GU did not change significantly. Mean adipocyte size was reduced, more at 4 than 24 weeks. At 4 week, expression of genes involved in fatty acid oxidation, CPT1b; cell proliferation, E2F1; and adiponectin were increased, whereas leptin was reduced (p<0.for all). Conclusion: Glycemic control and insulin sensitivity clearly improved 4 weeks after GBP, but adipocyte insulin sensitivity in vitro did not improve despite a reduction in adipocyte size. Thus the mechanisms for rapid improvement of T2D after GBP may occur mainly in other tissues than adipose.Clinical and metabolic characteristicsBaseline4-wks post surgery24-wks post surgeryAdipocyte in-vitro dataBaseline4-wks post surgery24-wks post surgeryBMI (kg/m2)37.3 ± 4A32.9 ± 3.3B28.3 ± 3.5CAdipocyte diameter (µm)110 ± 5.3A72.3 ± 10.3B92.5 ± 5.4CWeight (kg)105.5 ±14.5A93.4 ± 11.4B80.1 ± 11.1CGlucose uptake (fL/cell/sec)Waist hip ratio (cm)0.99 ± 0.07a0.97 ± 0.07a0.93 ± 0.07bbasal19.5 ± 4.316.6 ± 6.720.3 ± 3.8Body fat (%)41.2 ± 8.9A38.6 ± 8.9B30.7 ± 10.4C25 µU/ml Insulin23.1 ± 6.319.2 ± 7.629.8 ± 6.7HbA1c (mmol/mol)48 ± 6a39 ± 7b37 ± 4b1000 µU/ml Insulin31.4 ± 4.725.7 ± 10.739.4 ± 6.9Fasting glucose (mmol/L)7.4 ± 0.9A5.8 ± 0.6B5.4 ± 04CLipolysis (nmol gly-cerol/10E5 cells/h)HOMA-IR6.63 ± 0.5A2.59 ± 1.3B1.32 ± 0.5C0.5 µM Iso58.4 ± 16.253.2 ± 9.351.3 ± 12.9Matsuda index1.38 ± 0.3A2.77 ± 0.9B4.90 ± 2.1C0.5 µM Iso + 1µU/ml insulin33.1 ± 6.527.3 ± 6.941.7 ± 10.7Modified QUICKI0.29 ± 0.01A0.33 ± 0.3B0.38 ± 0.03C0.5 µM Iso + 100 µU/ml insulin26.4 ± 4.321.6 ± 5.433.1 ± 9.1Data are means ± SD. Body fat % measured by bioimpedance. Different letters indicated significant differences between the visits; lower case letter: p < 0,; upper case letter: p < 0,01. Iso, isoprenaline. Disclosure P. Katsogiannos: None. G.J. Boersma: None. P.G. Kamble: None. M.J. Pereira: None. P. Lundkvist: None. A. Karlsson: None. M. Sundbom: None. J.W. Eriksson: Employee; Spouse/Partner; Amgen Inc.. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp.. Research Support; Self; Bristol-Myers Squibb Company.