Insulin response to oral stimuli and glucose effectiveness increased in neuroglycopenia following gastric bypass

Abstract

Objective: Hyperinsulinemic hypoglycemia with neuroglycopenia is a rare complication following Roux-en-Y gastric bypass (RYGB) surgery for weight management. Insulin secretion and action in response to oral and intravenous stimuli in persons with and without neuroglycopenia following RYGB are evaluated in this study.

Methods: Cross-sectional cohort studies were performed at a single academic institution to assess insulin secretion and action during oral mixed meal tolerance test and intravenous glucose tolerance test (IVGTT).

Results: Insulin secretion was increased more following oral mixed meal than intravenous glucose in individuals with neuroglycopenia compared to the asymptomatic group. Reduced insulin clearance did not contribute to higher insulinemia. Glucose effectiveness at zero insulin, estimated during the IVGTT, was also higher in those with neuroglycopenia. Insulin sensitivity did not differ between groups.

Conclusions: Increased beta-cell response to oral stimuli and insulin-independent glucose disposal may both contribute to severe hypoglycemia after RYGB.

Figure 1

Mixed meal tolerance test (MMTT)-derived data and calculated values for (A) glucose (mg×dl^-1), (B) C-peptide (ng×ml^-1), (C) insulin (μU×ml^-1), (D) the corrected insulin response to glucose (CIR₃₀, 10×mU×ml×mg^-2),(E) C-peptide/glucose ratio (×10^-4), (F) insulin/glucose ratio (μU×10²×mg^-1), (G) insulin secretion rate (ISR, pmol×(kg×min)^-1), and (H) the composite insulin sensitivity index (CISI, dl×ml×(μU×mg)^-1) are provided. P-values were calculated by linear mixed models repeated measures analysis [A-C and E-G]. Boxplots with median (line), mean (x), interquartile range (box) and minimum and maximum (whiskers) are shown [D and H]. P-values were calculated by independent sample t-tests [D] and nonparametric variations (Mann-Whitney U-test) [H].

Figure 2

Intravenous glucose tolerance test (IVGTT)-derived values for (A) glucose (mg×dl^-1), (B) insulin (μU×ml^-1), (C) insulin/glucose ratio (μU×10²×mg^-1), (D) acute insulin response to glucose (AIRg, μU×min×ml^-1), (E) insulin sensitivity index [S_I, l0³× (mU×min)^-1], (F) disposition index (DI), (G) the relationship between AIRg and S_I, in individuals with neuroglycopenia (●) or in asymptomatic (○) persons, (H) glucose effectiveness at zero insulin (GEZI, min^-1) and (I) glucose effectiveness (S_g, min^-1),are provided. P-values were calculated by linear mixed models repeated measures analysis [A-C]. Boxplots with median (line), mean (x), interquartile range (box) and minimum and maximum (whiskers) are shown with P-values calculated by nonparametric variations (Mann-Whitney U-test) [D-F and H-I]. *P<0.05 versus asymptomatic group.

Figure 3

Comparison of neuroglycopenic subjects without diabetes prior to RYGB (NG-No-DM) (●) and asymptomatic (ASx) subjects (○). Mixed meal tolerance test (MMTT) [A-G] and Intravenous Glucose Tolerance Test (IVGTT)-derived [H-L] values for (A) glucose (mg×dl^-1), (B) C-peptide (ng×ml^-1), (C) insulin (μU×ml^-1), (D) C-peptide/glucose ratio (×10^-4), (E) insulin/glucose ratio (μU×10²×mg^-1), (F) insulin secretion rate (ISR, pmol×(kg×min)^-1), (G) the corrected insulin response to glucose (CIR₃₀, 10×mU×ml×mg^-2), (H) acute insulin response to glucose (AIRg, μU×min×ml^-1), (I) insulin sensitivity index [S_I, 10³× (mU×min)^-1], (J) disposition index (DI), (K) glucose effectiveness at zero insulin (GEZI, min^-1), and (L) glucose effectiveness (S_G, min^-1) are provided. P-values were calculated by linear mixed models repeated measures analysis [A-F]. Boxplots with median (line), mean (x), interquartile range (box) and minimum and maximum (whiskers) are shown. P-values were calculated by independent sample t-tests [G] and nonparametric variations (Mann-Whitney U-test) [H-L].

Figure 4

Comparison of participants with neuroglycopenia who manifest glucose concentratons less than or equal to 60 mg/dl during mixed meal tolerance test (NG-hypo-MMTT) (●) and asymptomatic (ASx) subjects (○). Mixed meal tolerance test (MMTT) [A-G] and Intravenous Glucose Tolerance Test (IVGTT)-derived [H-L] values for (A) glucose (mg×dl^-1), (B) C-peptide (ng×ml^-1), (C) insulin (μU×ml^-1), (D) C-peptide/glucose ratio (×10^-4), (E) insulin/glucose ratio (μU×10²×mg^-1), (F) insulin secretion rate (ISR, pmol×(kg×min)^-1), (G) the corrected insulin response to glucose (CIR₃₀, 10×mU×ml×mg^-2), (H) acute insulin response to glucose (AIRg, μU×min×ml^-1), (I) insulin sensitivity index [S_I, 10³× (mU×min)^-1], (J) disposition index (DI), (K) glucose effectiveness at zero insulin (GEZI, min^-1), and (L) glucose effectiveness (S_G, min^-1) are provided. P-values were calculated by linear mixed models repeated measures analysis [A-F]. Boxplots with median (line), mean (x), interquartile range (box) and minimum and maximum (whiskers) are shown. P-values were calculated by independent sample t-tests [G] and nonparametric variations (Mann-Whitney U-test) [H-L].