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 characteristics Baseline 4-wks post surgery 24-wks post surgery Adipocyte in-vitro data Baseline 4-wks post surgery 24-wks post surgery 
BMI (kg/m237.3 ± 4A 32.9 ± 3.3B 28.3 ± 3.5C Adipocyte diameter (µm) 110 ± 5.3A 72.3 ± 10.3B 92.5 ± 5.4C 
Weight (kg) 105.5 ±14.5A 93.4 ± 11.4B 80.1 ± 11.1C Glucose uptake (fL/cell/sec)    
Waist hip ratio (cm) 0.99 ± 0.07a 0.97 ± 0.07a 0.93 ± 0.07b basal 19.5 ± 4.3 16.6 ± 6.7 20.3 ± 3.8 
Body fat (%) 41.2 ± 8.9A 38.6 ± 8.9B 30.7 ± 10.4C 25 µU/ml Insulin 23.1 ± 6.3 19.2 ± 7.6 29.8 ± 6.7 
HbA1c (mmol/mol) 48 ± 6a 39 ± 7b 37 ± 4b 1000 µU/ml Insulin 31.4 ± 4.7 25.7 ± 10.7 39.4 ± 6.9 
Fasting glucose (mmol/L) 7.4 ± 0.9A 5.8 ± 0.6B 5.4 ± 04C Lipolysis (nmol gly-cerol/10E5 cells/h)    
HOMA-IR 6.63 ± 0.5A 2.59 ± 1.3B 1.32 ± 0.5C 0.5 µM Iso 58.4 ± 16.2 53.2 ± 9.3 51.3 ± 12.9 
Matsuda index 1.38 ± 0.3A 2.77 ± 0.9B 4.90 ± 2.1C 0.5 µM Iso + 1µU/ml insulin 33.1 ± 6.5 27.3 ± 6.9 41.7 ± 10.7 
Modified QUICKI 0.29 ± 0.01A 0.33 ± 0.3B 0.38 ± 0.03C 0.5 µM Iso + 100 µU/ml insulin 26.4 ± 4.3 21.6 ± 5.4 33.1 ± 9.1 
        
Clinical and metabolic characteristics Baseline 4-wks post surgery 24-wks post surgery Adipocyte in-vitro data Baseline 4-wks post surgery 24-wks post surgery 
BMI (kg/m237.3 ± 4A 32.9 ± 3.3B 28.3 ± 3.5C Adipocyte diameter (µm) 110 ± 5.3A 72.3 ± 10.3B 92.5 ± 5.4C 
Weight (kg) 105.5 ±14.5A 93.4 ± 11.4B 80.1 ± 11.1C Glucose uptake (fL/cell/sec)    
Waist hip ratio (cm) 0.99 ± 0.07a 0.97 ± 0.07a 0.93 ± 0.07b basal 19.5 ± 4.3 16.6 ± 6.7 20.3 ± 3.8 
Body fat (%) 41.2 ± 8.9A 38.6 ± 8.9B 30.7 ± 10.4C 25 µU/ml Insulin 23.1 ± 6.3 19.2 ± 7.6 29.8 ± 6.7 
HbA1c (mmol/mol) 48 ± 6a 39 ± 7b 37 ± 4b 1000 µU/ml Insulin 31.4 ± 4.7 25.7 ± 10.7 39.4 ± 6.9 
Fasting glucose (mmol/L) 7.4 ± 0.9A 5.8 ± 0.6B 5.4 ± 04C Lipolysis (nmol gly-cerol/10E5 cells/h)    
HOMA-IR 6.63 ± 0.5A 2.59 ± 1.3B 1.32 ± 0.5C 0.5 µM Iso 58.4 ± 16.2 53.2 ± 9.3 51.3 ± 12.9 
Matsuda index 1.38 ± 0.3A 2.77 ± 0.9B 4.90 ± 2.1C 0.5 µM Iso + 1µU/ml insulin 33.1 ± 6.5 27.3 ± 6.9 41.7 ± 10.7 
Modified QUICKI 0.29 ± 0.01A 0.33 ± 0.3B 0.38 ± 0.03C 0.5 µM Iso + 100 µU/ml insulin 26.4 ± 4.3 21.6 ± 5.4 33.1 ± 9.1 

Data 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.

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