Systematic ileal transposition in Zucker rats shows advantage for long segment distal transposition.

INTRODUCTION: The possibility of achieving diabetes remission through bariatric surgery has dramatically changed treatment options for this disease. Ileal transposition (IT), specifically designed to provoke diabetes remission, has so far shown great success in rodent studies. However, it remains uncertain which combination of ileal length and origin produces best results. METHODS: Forty male Zucker rats underwent transposition of 25% distal, 50% distal, and 50% proximal ileum or sham surgery. Glucose control, insulin, and glucagon-like peptide (GLP)-1 serum levels were analyzed after 1, 3, and 6 months. Body weight was recorded weekly. RESULTS: In relation to sham-operated animals, the 50% distal IT presented with improved glucose tolerance after 1, 3, and 6 months (2-way analysis of variance [ANOVA]: P < .05, < .0001, and < .0001, respectively). The 25% distal and 50% proximal IT only showed improved glucose control after 3 months, suggesting a fading effect in long-term observation (2-way ANOVA: P < .0001 for both). Glucose-stimulated GLP-1 levels were steadily elevated only in the 2 distal IT groups (Mann-Whitney sham versus 50% distal, P < .01, < .01, and < .05; sham versus 25% distal, P < .01, = .001, < .05 for 1, 3, and 6 months, respectively). IT had no impact on serum insulin levels. CONCLUSION: The current study restates the findings of improved glucose tolerance and GLP-1 stimulation after IT, but is the first to demonstrate a fading glycemic effect in long-term observation. Systematic comparison of length and ileal origin revealed that long and distal transposition delivers best results.

Long segment ileal transposition leads to early amelioration of glucose control in the diabetic obese Zucker rat.

INTRODUCTION: Fast delivery of food to the terminal ileum is thought to be pathophysiologically responsible for type 2 diabetes remission after obesity surgery. Imitating this effect, ileal transposition (IT) is designed as initiating diabetes remission for non-obese patients. AIM: To date, it is not clear which length of the transposed segment achieves the best glucose lowering results. As previous rodent data mostly rely on a 10 cm IT, the current study evaluated a long segment IT (20 cm) in the diabetic obese Zucker rat. MATERIAL AND METHODS: Twenty male diabetic obese Zucker rats (Crl:ZUC-Lepr(fa)) were randomly assigned to undergo either a long segment (20 cm; ∼ 50% of ileum) IT or sham surgery. Glucose control was determined by an oral glucose tolerance test (OGTT) on day -7, 0, 14 and 20. Analysis of the incretin hormones glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and insulin was included in the first and third OGTT. RESULTS: Ileal transposition animals showed an early improvement of glucose control after 14 days (area under the curve: IT vs. baseline 314.7 ±229.0 mmol/l × min vs. 564.6 ±268.5 mmol/l × min; p < 0.05). Compared to sham animals, glucose-stimulated GLP-1 and PYY levels were raised (5.75 ±3.73 pmol/l vs. 18.52 ±14.22 pmol/l, p < 0.05; 129.7 ±64.62 pmol/l vs. 164.0 ±62.26 pmol/l, p < 0.05). Body weight gain from postoperative day 5 was greater for sham animals (50.22 ±20.93 γ vs. 16.4 ±25.93 g; p < 0.01). CONCLUSIONS: Long segment IT shows a rapid rise in GLP-1 and PYY levels, thus leading to early amelioration of glucose control.