Role of the Entero-Insular Axis in the Pathogenesis of Idiopathic Reactive Hypoglycemia: A Pilot Study.
BACKGROUND
Idiopathic reactive hypoglycemia (IRH) is characterized by recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after meals. The underlying mechanisms remain obscure.


OBJECTIVE
This study aimed to investigate the response of the glucoregulatory and gastrointestinal hormones to an oral glucose load (OGTT) in individuals with documented IRH.


METHODS
This was a cross-sectional study composed of outpatients referred to "Federico II" University of Naples.


METHODS
We enrolled subjects with IRH documented by a mixed meal under ordinary life conditions and healthy subjects as controls.


METHODS
We measured plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), GIP, and glucagon response to a 75-g OGTT in cases and controls.


RESULTS
Ten IRH and eight control subjects were enrolled. During the OGTT, mean plasma glucose tended to be lower in IRH than in control subjects, reaching a statistically significant difference at 240 minutes (T240) (43 ± 1.6 vs 72 ± 0.3 mg/dL; P = .001). Accordingly, the insulin response was higher in IRH than in control subjects (P < .019) with a statistically significant difference (46%) at T90 (P = .045) and was associated with significantly lower glucagon levels in the late phase of the OGTT: at T120 (P = .031) and T180 (P = .048) in IRH than in control subjects. A greater GLP-1 response was found among IRH compared with control subjects (P = .005); GLP-1 peak was 2-fold higher in IRH individuals (9.77 ± 2.52 pmol/L) than in the control group (4.19 ± 0.53 pmol/L; P = .041). In the IRH group, GLP-1 peak inversely correlated with the nadir of plasma glucose (r = -0.66; P = .039). A multivariate analysis confirmed that GLP-1 peak independently predicted the plasma glucose nadir (β = -0.593; P = .026).


CONCLUSIONS
GLP-1 may play a significant role in the pathogenesis of idiopathic IRH.
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Roberta
R
Lupoli
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Mariella
M
Cotugno
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Ettore
E
Griffo
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Gabriella
G
Nosso
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Gabriele
G
Riccardi
Department of Clinical Medicine and Surgery, "Federico II" University, 80131 Naples, Italy.
Brunella
B
Capaldo
D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000473:pathology*; D007328:Insulin / Q000097:blood; D008297:Male; D010865:Pilot Projects
D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon