A 51-year-old male patient with type 2 diabetes (BMI 50.2 kg/m², A1C 8.0%) treated with metformin, sulfonylurea, and insulin underwent a laparoscopic RYGB for morbid obesity.

On the second postoperative day, a leakage from the gastro-jejunostomy was suspected because of fever and abdominal pain. Acute reoperation showed no firm signs of leakage, but nevertheless a percutaneous gastric tube was inserted into the bypassed gastric remnant. The tube served as the only route of nutrition during the following 3 weeks, after which the patient again was allowed peroral feeding through the gastric pouch according to a standard nutrition protocol (1,200 kcal/day). Treatment with insulin and metformin was temporarily required after the reoperation but could be discontinued 3 weeks postoperatively.

We examined the patient 5 weeks postoperatively, at which time the patient was fed perorally but still had the gastric tube. The patient had lost 14 kg (BMI 45.2 kg/m²). Informed consent was obtained prior to examination.

On 2 consecutive days at 8.30 A.M. after an overnight fast (8 h), a standard 200-ml liquid meal (Nutridrink; Nutricia) containing 300 kcal, with 16% protein, 49% carbohydrate, and 36% fat, was given over a period of 10 min, on the first day through the gastric tube and on the second day perorally. Blood samples were drawn from an antecubital vein at 15- to 30-min intervals (Fig. 1).

Plasma concentrations and iAUC for glucose, insulin, C-peptide, glucagon, total glucagon-like peptide-1 (GLP-1), intact glucose-dependent insulinotropic polypeptide (GIP), PYY, and FFAs after peroral and gastroduodenal feeding are shown in Fig. 1.

Plasma glucose concentration peaked earlier and returned more rapidly to fasting values after peroral than gastroduodenal feeding, as illustrated by a markedly reduced 2-h plasma glucose concentration (7.8 vs. 11.1 mmol/l). iAUC_Glu was noticeably lower after peroral feeding. The peak values of plasma insulin and C-peptide were higher after peroral than gastroduodenal feeding (fourfold and twofold, respectively) and iAUC_insulin and iAUC_Cpeptide were also clearly elevated. IGI was improved after peroral feeding (115 vs. 72 pmol/mmol), and the iAUC_Cpeptide/Glu ratio was more than twofold increased (0.90 vs. 0.40 nmol/mmol). HOMA-IR remained unchanged on the 2 examination days (3.3 vs. 3.5).

GLP-1 plasma concentration peaked simultaneously after peroral and gastroduodenal feeding, but the peak value was more than threefold increased (87 vs. 28 pmol/l), and iAUC_GLP-1 was nearly fivefold increased after peroral feeding. Insulin and GLP-1 correlated strongly after peroral (r = 0.92, P < 0.001) but not gastroduodenal (r = 0.55, P = 0.08) feeding. Plasma concentrations of glucagon and intact GIP were similar on both days. Responses of PYY and FFAs are depicted in the figure.

Rapid improvement in glucose tolerance after RYGB surgery is a clinical reality (²). Here, we report important differences in β-cell function and glucose metabolism after peroral compared with gastroduodenal feeding in a patient with RYGB and a gastrostomy, where differences in insulin sensitivity, weight loss, and caloric restriction can be ruled out as explanations for the improved glucose tolerance.

Our results show marked improvement in glucose tolerance with near normalization of 2-h postprandial plasma glucose value and a 33% reduction in iAUC_Glu after peroral feeding compared with gastroduodenal feeding. In contrast, during gastroduodenal feeding glucose tolerance was diabetic with a 2-h postprandial plasma glucose value ∼11 mmol/l. The improvement was accompanied by a twofold increase in β-cell secretory response (AUC_Cpeptide/Glu), which was associated with a fivefold increase in iAUC_GLP-1. Insulin and GLP-1 concentrations during peroral feeding were strongly correlated, which is suggestive of a causal relationship. Interestingly, the insulin and C-peptide response curves found after gastroduodenal feeding resemble the responses found in type 2 diabetic patients, whereas the response curves after peroral feeding are similar to those found in healthy control subjects (⁴). The emptying time is likely to be slower after feeding into the bypassed gastric remnant, which could explain the slower peak in plasma glucose observed after gastroduodenal feeding but would also, per se, be expected to result in decreased postprandial glucose excursions.

The observed improvements in glucose tolerance and GLP-1 secretion are in concordance with earlier findings from patients examined before and after RYGB surgery (^{5, B6, B7, B8, B9, B10, B11, B12}–¹³). Regarding GIP, some studies have demonstrated increased (⁷,¹⁰) and others decreased (⁹,¹³) responses after RYGB. In our patient, GIP responses were similar on the 2 days, suggesting that changes in GIP were not responsible for the differences in insulin secretion and glucose tolerance. Also glucagon responses were similar.

In conclusion, our results suggest that RYGB has a direct beneficial effect on postprandial glucose metabolism, most likely due to an increased insulin secretion caused by the massive increase in GLP-1 that is probably due to the rapid exposure of L-cells in the distal small intestine to nutrients (¹⁴). It has been suggested that duodenal exclusion inherent in the RYGB somehow might be responsible for the improvement in glucose tolerance (¹⁵). In this respect, it is of interest that the secretion of the upper jejunal hormone, GIP, was similar during peroral or gastroduodenal feeding.

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No potential conflicts of interest relevant to this article were reported.