Endoscopic Duodenal-Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal-jejunal bypass liner (DJBL). Seventeen obese patients (BMI 30-50 kg/m(2)) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA(1c) and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment. At 24 weeks after implantation, patients had lost 12.7 +/- 1.3 kg (p < 0.01), while HbA(1c) had improved from 8.4 +/- 0.2 to 7.0 +/- 0.2 % (p < 0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6 +/- 0.5 vs. 9.0 +/- 0.5 vs. 8.6 +/- 0.5 mmol/L and 1,999 +/- 85 vs. 1,536 +/- 51 vs. 1,538 +/- 72 mmol/L/min, both p < 0.01). In parallel, the glucagon response decreased (23,762 +/- 4,732 vs. 15,989 +/- 3,193 vs. 13,1207 +/- 1,946 pg/mL/min, p < 0.05) and the GLP-1 response increased (4,440 +/- 249 vs. 6,407 +/- 480 vs. 6,008 +/- 429 pmol/L/min, p < 0.01). The GIP response was decreased at week 24 (baseline-115,272 +/- 10,971 vs. week 24-88,499 +/- 10,971 pg/mL/min, p < 0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation. The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.