Koch, Timothy R.

Objective: An endoscopically placed duodenal-jejunal bypass liner (DJBL) may provide a safe adjunctive therapy for those with poorly controlled type 2 diabetes mellitus (T2DM) and obesity. Background: Although some endoscopic therapies have been shown to improve glycemic indices secondary to weight loss, small bowel interventions may have direct metabolic effects. A meta-analysis of observational studies demonstrated reduction in HbA1c by 1.3% at 1 year after DJBL in patients with T2DM and obesity. Methods: This was a multicenter, double-blind, randomized, sham-controlled trial comparing DJBL to sham procedure with medical management and lifestyle modification. Primary endpoints included mean difference in changes in HbA1c at 12 months between arms, and device-related serious adverse events (SAEs). Secondary endpoints included percent total weight loss (%TWL) and subjects achieving HbA1c≤7% and TWL≥5% at 12 months. Results: Three hundred twenty subjects were randomized to DJBL (n=212) and sham (n=108). Baseline HbA1c and BMI were 8.79±0.92% and 38.45±5.75 kg/m 2 . On modified intent-to-treat analysis, change in HbA1c at 12 months was −1.10±1.45% and −0.28±1.54% for DJBL and sham groups, respectively ( P =0.0004). Rate of device-related SAEs was 9.4% including intolerance (3.7%), hemorrhage (2.8%), and hepatic abscess (2.3% stopping study early). At 12 months, DJBL group experienced greater weight loss compared with sham (7.7±9.6% TWL and 2.1±5.4% TWL, respectively; P <0.0001), with significantly more patients achieving HbA1c ≤ 7% (28.3% vs. 9.4%; P <0.0003) and TWL ≥ 5% (60.4% vs. 21.3%; P <0.0001). Conclusions: DJBL met primary glycemic control efficacy and primary safety endpoints, while providing clinically significant weight loss, and comorbidity improvement.

A 30-year-old female underwent vertical sleeve gastrectomy. Postoperatively, hypercupremia and elevated ceruloplasmin were identified. Further testing revealed normal blood levels of transaminases, alkaline phosphatase, and albumin. She stopped ingestion of multivitamins, began a copper-free multivitamin, and then began a low copper diet, but with no improvement in hypercupremia. Protein electrophoresis was normal with no M-spike. Urinary copper excretion was normal at 0.24 micromol/24 hours (normal: < 0.55), and there were no Kayser-Fleischer rings on slit lamp examination. Two years postoperatively, she lost 44% of excess preoperative weight and she began zinc sulfate before meals twice daily (115 mg elemental Zinc/day). At 2 months and 8 months later, plasma copper and ceruloplasmin had essentially normalized. Increased production of ceruloplasmin could have been a response to significant weight loss or the presence of nonalcoholic steatohepatitis. The mechanism of zinc’s beneficial effect is uncertain but may be related to suppressing hepatic synthesis of or secretion of ceruloplasmin.