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The Journal of Clinical Endocrinology and Metabolism logoLink to The Journal of Clinical Endocrinology and Metabolism
. 2008 Oct 28;94(1):39–44. doi: 10.1210/jc.2008-1263

Increased Glucagon-Like Peptide-1 Secretion and Postprandial Hypoglycemia in Children after Nissen Fundoplication

Andrew A Palladino 1, Samir Sayed 1, Lorraine E Levitt Katz 1, Paul R Gallagher 1, Diva D De León 1
PMCID: PMC2630870  PMID: 18957502

Abstract

Context: Postprandial hypoglycemia (PPH) is a frequent complication of Nissen fundoplication in children. The mechanism responsible for the PPH is poorly understood, but involves an exaggerated insulin response to a meal and subsequent hypoglycemia. We hypothesize that increased glucagon-like peptide-1 (GLP-1) secretion contributes to the exaggerated insulin surge and plays a role in the pathophysiology of this disorder.

Objective: The aim of the study was to characterize glucose, insulin, and GLP-1 response to an oral glucose load in children with symptoms of PPH after Nissen fundoplication.

Design: Ten patients with suspected PPH and a history of Nissen fundoplication and eight control subjects underwent a standard oral glucose tolerance test at The Children’s Hospital of Philadelphia. Blood glucose (BG), insulin, and intact GLP-1 levels were obtained at various time points.

Participants: Children ages 4 months to 13 years old were studied.

Main Outcome Measures: Change scores for glucose, insulin, and intact GLP-1 were recorded after an oral glucose tolerance test.

Results: All cases had hypoglycemia after the glucose load. Mean BG at nadir (± sd) was 46.7 ± 11 mg/dl for cases (vs. 85.9 ± 21.3 mg/dl; P < 0.0005). Mean change in BG from baseline to peak (± sd) was 179.3 ± 87.4 mg/dl for cases (vs. 57.8 ± 39.5 mg/dl; P = 0.003). Mean change in BG (± sd) from peak to nadir was 214.4 ± 85.9 mg/dl for cases (vs. 55.9 ± 41.1 mg/dl, P < 0.0005). Mean change in insulin (± sd) from baseline to peak was 224.3 ± 313.7 μIU/ml for cases (vs. 35.5 ± 22.2 μIU/ml; P = 0.012). Mean change in GLP-1 (± sd) from baseline to peak was 31.2 ± 24 pm (vs. 6.2 ± 9.5 pm; P = 0.014).

Conclusions: Children with PPH after Nissen fundoplication have abnormally exaggerated secretion of GLP-1, which may contribute to the exaggerated insulin surge and resultant hypoglycemia.


Children with post-prandial hypoglycemia after Nissen fundoplication have abnormally exaggerated secretion of glucagon-like peptide-1, which may contribute to the amplified insulin surge and resultant hypoglycemia.


Dumping syndrome is a frequent complication of Nissen fundoplication, a surgery performed for severe gastroesophageal reflux. It has been estimated that up to 30% of children with Nissen fundoplication develop dumping syndrome (1). In children, this syndrome is characterized by severe postprandial hypoglycemia (PPH), or late dumping syndrome, with absent or less severe gastrointestinal symptoms of early dumping syndrome. If unrecognized, hypoglycemia can lead to seizures, developmental delays, and permanent brain damage. The mechanism responsible for the PPH is not fully understood, but is thought to involve reduced postprandial gastric relaxation and accelerated gastric emptying (2), resulting in the precipitous emptying of hyperosmolar, carbohydrate-containing solutions from the stomach into the upper small bowel (3) and subsequent hyperglycemia. Although the occurrence of postprandial hyperglycemia has been blamed for the later hypoglycemia, our observations in children with PPH after Nissen fundoplication have shown that peak insulin levels after a meal are proportionally higher than the degree of hyperglycemia (4), suggesting that other factors may contribute to the hyperinsulinemia. Recently, PPH has been recognized to be a severe complication of gastric bypass surgery (5,6). An exaggerated incretin and insulin response has been described to be part of the pathophysiology in these patients (7,8), as well as pancreatic islet hyperplasia (5,6). Similarly, studies in adults with PPH after partial gastrectomy have implicated excessive release of glucagon-like peptide-1 (GLP-1) leading to exaggerated insulin release as a potential cause of the PPH observed in this population (7,9,10,11).

GLP-1 is an insulinotropic (incretin) hormone secreted by intestinal L cells that potentiate glucose-stimulated insulin release by pancreatic ß-cells (for a complete review, see Ref. 12). In addition to enhancing glucose-stimulated insulin secretion, GLP-1 has other actions that are complementary to the incretin effect, including inhibition of glucagon secretion (13,14), hepatic glucose production (15,16), gastric emptying (17,18), and appetite (19,20). Furthermore, in animal models, exogenous administration of GLP-1 receptor agonists has been shown to result in increased pancreatic β-cell mass (12). The major physiological stimulus to L cells is nutrient ingestion, with circulating levels of GLP-1 rising by 2- to 3-fold in response to a mixed meal in adult human subjects (21). The regulation of GLP-1 secretion by ingested nutrients is complex and is thought to involve indirect vagal pathways as well as direct luminal stimulation of intestinal L cells (22). The secretion of GLP-1 is related to the rate of gastric emptying (9,23). The nutrient composition of the meal influences GLP-1 secretion as well; thus, simple carbohydrates and fats stimulate GLP-1 secretion, whereas pure complex carbohydrates and protein do not appear to do so in humans when taken individually (24,25).

We hypothesize that in children with Nissen fundoplication, the rapid emptying of a meal into the intestine results in inappropriately increased GLP-1 secretion, thereby triggering an exaggerated insulin surge and subsequent hypoglycemia. If our hypothesis proves true, GLP-1 may be a target for future therapies for affected children.

Subjects and Methods

Subjects

Ten subjects, aged 4 months to 13 yr, suspected of having PPH were recruited from the outpatient and inpatient endocrinology services at The Children’s Hospital of Philadelphia. Nine of the 10 subjects had a Nissen fundoplication for severe gastroesophageal reflux; one subject had a history of gastric pull-through surgery for a tracheoesophageal fistula. We recruited eight control subjects, six of whom were children undergoing evaluation for possible hypoglycemia not due to dumping syndrome, and two subjects with severe gastroesophageal reflux were studied before Nissen fundoplication and gastrostomy tube placement with no history of hypoglycemia. Exclusion criteria for case subjects consisted of fasting hypoglycemia, liver disease and malabsorption, and bowel abnormalities. Exclusion criteria for control subjects consisted of type 1 diabetes mellitus, type 2 diabetes mellitus, insulin resistance, and obesity (body mass index > 25 kg/m2). The study was approved by The Children’s Hospital of Philadelphia institutional review board, and consent was obtained from all participants.

Methods

All subjects were admitted to the Clinical and Translational Research Center inpatient unit the night before the study. The following day, they were administered an oral glucose tolerance test (OGTT). All subjects received 1.75 g/kg (75 g maximum) of glucose (Glucola; Thermo Fisher Scientific-NERL Clinical Diagnostics, East Providence, RI) either by mouth or via gastrostomy tube. For the formula tolerance test, subjects received between 3 and 12 ounces of Pediasure (Abbott Laboratories, Columbus, OH) or their home formula orally or via gastrostomy tube. Blood glucose and insulin levels were obtained at 0, 10, 20, 30, 60, 90, 120, and 180 min. GLP-1 levels were obtained at 0, 10, 20, 30, 60, and 120 min.

Assays

Venous blood glucose was measured using a Siemens Rapid Point 400 Blood Gas analyzer (Siemens Healthcare Diagnostics, Deerfield, IL). The analyzer has a resolution of 1 mg/dl (0.06 mmol/liter) and a within-run sd of ± 4 mg/dl (0.22 mmol/liter).

Plasma insulin was measured using the in vitro diagnostic grade insulin ELISA from ALPCO Diagnostics (Salem, NH). The assay has an analytical sensitivity of 0.798 μIU/ml (5.7 pmol/liter) and an intraassay coefficient of variation of less than 5%.

Plasma intact GLP-1 was measured using the GLP-1 ELISA kit (Millipore; Linco Research, St. Charles, MO). The kit has an analytical sensitivity of 2 pm and an intraassay coefficient of variation of less than 10%. Ten microliters of dipeptidyl peptidase IV inhibitor (Millipore) per milliliter of blood were added to samples immediately after collection to stop the degradation of GLP-1.

Statistical analysis

We performed a cross-sectional analysis of metabolic variables at baseline and in response to a glucose load in all subjects. In addition, the same metabolic parameters in response to a formula meal were analyzed in subjects with PPH. Change scores were calculated for blood glucose change from baseline to peak, blood glucose change from peak to nadir, insulin change from baseline to peak, and GLP-1 change from baseline to peak. Histograms and Kolmogorov-Smirnov one-sample tests indicated that several of the scores had skewed distributions. Results are therefore presented as median and range, as well as mean ± sd, and nonparametric tests are used. Differences between the two groups in these change scores were examined using Mann-Whitney tests. The strength of the linear relationship between these change scores was examined using Spearman correlation coefficients.

Results

Case subjects were comprised of 10 children (0 female) aged 4 months to 13 yr (47 ± 43 months) (Table 1), suspected of having PPH after Nissen fundoplication (n = 9) or gastric pull-through surgery (n = 1). The mean duration from surgery to the time of the study was 38 ± 45 months. Eight control subjects (four female) aged 15 to 69 months (39 ± 17 months) were recruited. The final diagnoses of the control subjects were: ketotic hypoglycemia (n = 5), possible defect in fatty acid oxidation (n = 1), and gastroesophageal reflux (n = 2). There was no statistically significant difference between the ages of the case subjects compared with control subjects.

Table 1.

Demographics of cases and controls including OGTT and formula tolerance test route of administration and formula information

Age (months) Gender Weight (kg) OGTT via FTT via Formula Formula volume (ml) Grams of carbohydrate/100 ml of formula Final diagnosis
Case no.
1 41 M 14.4 PO PO Pediasure 90 12.7 PPH
2 81 M 24 PO PO Pediasure 250 12.7 PPH
3 33 M 11.8 GT GT Elecare 200 7 PPH
4 4 M 6 GT PPH
5 34 M 14 PO PO Neocate 120 7.7 PPH
6 28 M 9 PO PO Pediasure 120 12.7 PPH
7 22 M 11.8 PO/GT PPH
8 45 M 14.5 PO/NG PO/NG Pediasure 350 12.7 PPH
9 24 M 10.6 PO/GT PO/GT Peptamen Jr. 135 13.7 PPH
10 155 M 36.6 GT GT Nutren 2.0 200 19 PPH
11 43 M 13.7 PO Peptamen Jr. 96 13.7 PPH
Controls
1 64 M 14 NG GERD
2 30 F 9.6 PO GERD
3 15 M 9.9 PO KH
4 55 F 17.6 PO KH
5 56 M 20 PO KH
6 32 F 10 PO KH
7 29 M 12 PO Possible FAO disorder
8 34 F 14.2 PO KH

FTT, Formula tolerance test; PO, per os (by mouth); GT, gastrostomy tube; NG, nasogastric; KH, ketotic hypoglycemia; FAO, fatty-acid oxidation; M, male; F, female; GERD, gastroesophageal reflux disease. 

In the postabsorptive state, case and control subjects received 1.75 g/kg of glucose either by mouth or via gastrostomy tube. Baseline blood glucose levels were not different in cases and controls [79 ± 7.9 mg/dl (4.4 ± 0.44 mmol/liter) vs. 84 ± 5.8 mg/dl (4.7 ± 0.32 mmol/liter); P = 0.17]. Blood glucose rose more quickly and to a higher level in case subjects compared with controls. Mean change in blood glucose from baseline to peak (± sd) was 179.3 ± 87.4 mg/dl (10 ± 4.9 mmol/liter) in cases compared with 57.8 ± 39.5 mg/dl (3.2 ± 2.2 mmol/liter) in controls (P = 0.003). Similarly, after peaking, blood glucose dropped more significantly in cases compared with controls. Mean change in blood glucose (± sd) from peak to nadir was 214.4 ± 85.9 mg/dl (11.9 ± 4.8 mmol/liter) in cases compared with 55.9 ± 41.1 mg/dl (3.1 ± 2.3 mmol/liter) in controls (P < 0.0005). Blood glucose was significantly higher (P < 0.05) in cases compared with controls at 30 and 60 min (Fig. 1A). Hypoglycemia occurred in all cases at a median time of 120 min after the glucose load (Table 2). None of the control subjects had hypoglycemia during the study. Mean blood glucose at nadir (± sd) was 46.7 ± 11 mg/dl (2.6 ± 0.6 mmol/liter) for cases compared with 85.9 ± 21.3 mg/dl (4.8 ± 1.2 mmol/liter) for controls (P < 0.0005).

Figure 1.

Figure 1

A, Mean blood glucose values ± sem in cases (solid triangles) and controls (solid circles) at time points 0, 10, 20, 30, 60, 90, 120, and 180 min after OGTT. A significant difference between cases and controls is reached at 30 and 60 min (P < 0.05). B, Mean plasma insulin values ± sem in cases and controls at time points 0, 10, 20, 30, 60, 90, 120, and 180 min after OGTT. A significant difference between cases and controls is reached at 30 and 60 min (P < 0.05). C, Mean intact plasma GLP-1 values ± sem in cases and controls at time points 0, 10, 20, 30, 60, 90 (cases only), and 120 min after OGTT. Intact GLP-1 levels were not measured at 90 min in controls. A significant difference between cases and controls is reached at 30 min (P < 0.05).

Table 2.

Glucose, insulin, and GLP-1 data after OGTT in cases compared with controls

Cases
Controls
P value
Median time (min) Mean ± sd (median: range) Median time (min) Mean ± sd (median: range)
Glucose
 Baseline 0 79 ± 7.9 mg/dl (78: 64–90) 0 84 ± 5.8 mg/dl (86.5: 74–91) 0.17
 Peak 30 261.1 ± 82 mg/dl (258: 168–416) 30 141.8 ± 41.5 mg/dl (151: 85–201) 0.001
 Nadir 120 46.7 ± 11 mg/dl (47.5: 23–57) 120 85.9 ± 21.3 mg/dl (77.5: 59–121) <0.0005
Insulin
 Baseline 0 4 ± 1.9 μ IU/ml (3: 3–8) 0 4 ± 1.3 μ IU/ml (3: 3–6) 0.92
 Peak 30 228.3 ± 313.7 μ IU/ml (142.6: 10.5–1047) 30 33.7 ± 24.7 μ IU/ml (38.4: 3–62.3) 0.005
GLP-1
 Baseline 0 10.7 ± 11.1 pm (8.2: 1.1–33.7) 0 7.8 ± 2.5 pm (7.1: 5.8–12.5) 0.63
 Peak 10 41.9 ± 24.7 pm (43.3: 13.1–75.4) 10 14 ± 9.5 pm (11.5: 6.4–33.2) 0.014

Baseline plasma insulin levels were not different in the two groups [4 ± 1.9 μIU/ml (28.7 ± 13.6 pmol/liter) vs. 4 ± 1.3 μIU/ml (28.7 ± 9.3 pmol/liter), P = 0.92]. After a glucose load, plasma insulin levels increased, reaching a peak at median time of 30 min in both groups. Plasma insulin levels were significantly higher in cases compared with controls at 30 min [124.2 ± 85.7 μIU/ml (891.1 ± 614.9 pmol/liter) in cases compared with 32.9 ± 25.7 μIU/ml (236.1 ± 184.4 pmol/liter) in controls; P = 0.05] and at 60 min [205.5 ± 347.7 μIU/ml (1474.5 ± 2494.7 pmol/liter) in cases compared with 17.9 ± 13.5 μIU/ml (128.4 ± 96.9 pmol/liter) in controls; P = 0.043] (Fig. 1B). The mean change in insulin (± sd) from baseline to peak was 224.3 ± 313.7 μIU/ml (1609.4 ± 2250.8 pmol/liter) in cases compared with 35.5 ± 22.2 μIU/ml (254.7 ± 159.3 pmol/liter) in controls (P = 0.012). In one of the subjects, insulin reached a peak level of 1047.2 μIU/ml (7513.7 pmol/liter). Plasma insulin levels were appropriately suppressed after the hypoglycemia, suggesting normal regulation of insulin secretion by glucose.

We explored the pattern of GLP-1 secretion in these children with PPH, hypothesizing that increased GLP-1 secretion resulting from the rapid gastric emptying contributes to the exaggerated insulin response. Baseline intact GLP-1 levels were not different in cases vs. controls (10.7 ± 11.1 pm vs. 7.8 ± 2.5 pm; P = 0.63). Intact GLP-1 levels rise modestly after a glucose load in control children, from a baseline level of 7.8 ± 2.5 pm to a peak level of 14 ± 9.9 pm at median time of 10 min. In contrast to this modest response in normal children, children with PPH exhibit a higher and more prolonged response. Intact GLP-1 levels are higher in cases compared with controls over all time points after the glucose load, reaching a significant difference at 30 min (27.5 ± 15.8 pm in cases compared with 10 ± 5.5 pm in controls; P = 0.022) (Fig. 1C). GLP-1 peak and nadir glucose were strongly correlated (Spearman r = −0.8; P = 0.001). The mean change in GLP-1 (± sd) from baseline to peak was 31.2 ± 24 pm in cases compared with 6.2 ± 9.5 pm in controls (P = 0.014). There were no statistically significant differences identified in the responses of subjects that received glucose either by mouth or by gastrostomy tube.

A formula tolerance test was performed in nine children (eight with Nissen fundoplication, one with gastric pull-through) with a history of PPH. Due to limitations on the allowable amount of blood to be drawn, we were unable to obtain a full set of labs on all case subjects. Control data were not obtained. Subjects received Pediasure or their home formula by mouth or via gastrostomy tube (Table 1). In response to the formula ingestion, blood glucose peaked at a median time of 20 min with a mean peak blood glucose (± sd) of 209.4 ± 87.1 mg/dl (11.6 ± 4.8 mmol/liter) (Fig. 2). The change in blood glucose from baseline to peak was 134.3 ± 91.4 mg/dl (7.5 ± 5.1 mmol/liter), and from peak to nadir was 147.9 ± 95.5 mg/dl (8.2 ± 5.3 mmol/liter). The mean peak insulin level (± sd) was 275.9 ± 334.4 μIU/ml (1979.6 ± 2399.3 pmol/liter). The change in insulin levels from baseline to peak was 272.6 ± 334.3 μIU/ml (1955.9 ± 2398.6 pmol/liter). Intact GLP-1 was measured in eight of our cases. The peak value for intact GLP-1 (± sd) was 51.4 ± 30.1 pm. The change in intact GLP-1 from baseline to peak was 41.1 ± 31.1 pm. There were no statistically significant differences identified in the responses of subjects that received formula either by mouth or gastrostomy tube.

Figure 2.

Figure 2

Mean blood glucose (solid circles, solid line), plasma insulin (solid square, gray line), and plasma intact GLP-1 (solid triangle, dashed line) values ± sem in cases at time points 0, 10, 20, 30, 60, 90, 120, and 180 min (glucose and insulin only at 180 min) after a formula tolerance test. This graph demonstrates the temporal relationship between glucose, insulin, and GLP-1 in children with Nissen fundoplication after a formula bolus.

The response of GLP-1 to a mixed meal in children with PPH after Nissen fundoplication is similar to their GLP-1 response after an oral glucose load.

Discussion

Our results show that children with PPH after Nissen fundoplication experience increased insulin levels and hypoglycemia compared with controls after an enteric glucose load. Additionally, they have an abnormally exaggerated secretion of GLP-1. This increased secretion may contribute to the exaggerated insulin surge and resultant hypoglycemia. The higher glucose levels after OGTT in our postsurgical patients may also contribute to higher GLP-1-mediated insulin release. Formula tolerance tests in cases also showed exaggerated secretion of both insulin and GLP-1 similar to that seen with an oral glucose load, suggesting that the rapid transport of nutrients in addition to glucose to the small intestine is capable of stimulating the L cells, resulting in abnormally elevated levels of GLP-1 and subsequently elevated insulin levels. The fact that these children received mostly liquid meals after the surgery may further exacerbate the problem because it is known that a liquid meal results in significantly more GLP-1 release than a solid meal of identical composition (26).

There is no evidence of an underlying disorder of fasting adaptation in the population studied. Fasting adaptation was evaluated as part of their initial evaluation and was found to be normal. In addition, baseline levels for all of the parameters studied were no different than those from the control subjects. Furthermore, in response to the hypoglycemia, insulin secretion was appropriately suppressed.

Most studies to date have focused on the beneficial effects of GLP-1 as an insulinotropic hormone. Little is known about the potential role of GLP-1 in the pathogenesis of hypoglycemic disorders. In patients with type 2 diabetes mellitus, acute (27,28) or chronic (29) sc administration of GLP-1 has not been associated with hypoglycemia. However, iv or sc administration of GLP-1 combined with iv glucose has been shown to induce hypoglycemia in healthy subjects (28,30). In fasted healthy subjects, sc injection of GLP-1 resulted in a fall of plasma glucose concentrations below the normal range (31). Increased levels of endogenous GLP-1 in pathological conditions have also been associated with a hypoglycemic response. In one report, a GLP-1- and somatostatin-secreting tumor resulted in postprandial hyperglycemia followed by symptomatic hypoglycemia in a 45-yr-old woman (32). Additionally, the elevated plasma levels of GLP-1 observed in partially gastrectomized adult subjects and in adult individuals after gastric bypass surgery in response to an oral glucose load or mixed meal have been proposed to be responsible for the PPH observed in this population by stimulating insulin secretion (7,8,9,10,11). To our knowledge, this is the first report in children of increased secretion of GLP-1. These findings support a potential role for GLP-1 in the pathogenesis of PPH after Nissen fundoplication in a pediatric population.

Limitations of our study include the absence of a control group for the formula tolerance test and history of fasting hypoglycemia in our control group for the OGTT. One important advantage of our study is the inclusion of children of comparable age because the metabolic response to oral glucose is likely to be influenced by the age of the subject. Because our study population consists of children, it is difficult to justify subjecting healthy control subjects to an invasive study such as an OGTT for which there would be no direct benefit to the subject. Glucose responses to the OGTT in our control population are not different from those of historical controls (33,34). There are very limited data on stimulated intact GLP-1 levels in normal adults, and these data do not exist in children. The intact GLP-1 response to a glucose load in our control population is similar to the levels reported for normal adult subjects in response to a mixed meal and to an oral glucose load (21,35).

The observation that GLP-1 secretion is significantly increased in children with PPH has important pathophysiological implications. An interesting question that should be addressed with further studies is the role of the elevated GLP-1 levels in non-β-cell targets. It has been previously reported (36) that in children with PPH after Nissen fundoplication there is inadequate glucagon response to hypoglycemia resulting in sustained hypoglycemia. It is possible that in addition to contributing to the exaggerated insulin response, GLP-1 contributes to the hypoglycemia by its effects on other targets, such as suppression of glucagon secretion or increase of peripheral glucose uptake. Furthermore, there have been reports of refusal to eat in children with dumping syndrome after Nissen fundoplication (37); given the central appetite suppressive effects of GLP-1 (19,20), its elevated levels in response to meals can explain this symptom.

Therapies that have been tried in the treatment of dumping syndrome include cornstarch, pectin, octreotide, and dietary manipulations (1,38,39,40). These therapies have had mixed results. We have had some success with the use of acarbose, an α-glucosidase inhibitor that delays the absorption of complex carbohydrates (4). However, the gastrointestinal side effects of this drug make it unfavorable for many children. Thus, many children require a regimen of continuous enteral feedings to avoid hypoglycemia but continue to be at high risk of hypoglycemic events if feedings are abruptly stopped. If the GLP-1 surge is responsible for the exaggerated insulin surge and other potential effects resulting in hypoglycemia, it is plausible that an antagonist of the GLP-1 receptor may be a potential therapy for these children.

Our data show that children with symptoms of PPH after Nissen fundoplication exhibit an exaggerated increase in secretion of GLP-1 in response to both glucose and formula boluses, which may contribute to the exaggerated insulin surge and resultant hypoglycemia. To our knowledge, this is the first study in children implicating GLP-1 in the pathogenesis of hypoglycemia. Further studies to determine the relationship between the exaggerated GLP-1 response and the subsequent hypoglycemia are needed.

Acknowledgments

The authors acknowledge the contribution of Clinical Translational and Research Center (CTRC) staff, particularly, the inpatient nurses and the biochemical laboratory technicians, as well as the nurses in The Children’s Hospital of Philadelphia Hyperinsulinism Center.

Footnotes

This work was supported by National Institutes of Health Grant 1K23 DK073663-01 (to D.D.D.L.) and by The Children’s Hospital of Philadelphia CTRC (Grant UL1-RR-024134) from the National Center for Research Resources.

Author Disclosure Summary: A.A.P., S.S., L.E.L.K., P.R.G., and D.D.D.L. have nothing to disclose.

First Published Online October 28, 2008

Abbreviations: GLP-1, Glucagon-like peptide-1; OGTT, oral glucose tolerance test; PPH, postprandial hypoglycemia.

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