Post-prandial hypoglycemia results from a non-glucose-dependent inappropriate insulin secretion in Roux-en-Y gastric bypassed patients.

BACKGROUND: After Roux-en-Y gastric bypass (RYGB), hypoglycemia can occur and be associated with adverse events such as intense malaise and impaired quality of life. OBJECTIVE: To compare insulin secretion, sensitivity, and clearance between two groups of patients, with or without hypoglycemia, after an oral glucose tolerance test (OGTT 75-g), and also to compare real-life glucose profiles within these two groups. SETTING: Bariatric surgery referral center. METHODS: This study involves a prospective cohort of 46 consecutive patients who complained of malaise compatible with hypoglycemia after RYGB, in whom an OGTT 75-g was performed. A plasma glucose value of lower than 2.8 mmol/L (50 mg/dl) between 90 and 120 min after the load was considered to be a significant hypoglycemia. The main outcome measures were insulin sensitivity, beta-cell function, and glycemic profiles during the test. Glucose parameters were also evaluated by continuous glucose monitoring (CGM) in a real-life setting in 43 patients. RESULTS: Twenty-five patients had plasma glucose that was lower than 2.8 mmol/L between 90 and 120 from the load (HYPO group). Twenty-one had plasma glucose that was higher than 2.8 mmol/L (NONHYPO group). The HYPO patients were younger, had lost more weight after RYGB, were less frequently diabetic before surgery, and displayed higher early insulin secretion rates compared with the NONHYPO patients after the 75-g OGTT, and they had lower late insulin secretion rates. The HYPO patients had lower interstitial glucose values in real life, which suggests that a continuum exists between observations with an oral glucose load and real-life interstitial glucose concentrations. CONCLUSIONS: This study suggests that HYPO patients after RYGB display an early increased insulin secretion rate when tested with an OGTT. CGM shows that HYPO patients spend more time below 3.3 mmol/L when compared with NONHYPO patients. This phenotype of patients should be monitored carefully after RYGB.

Glucose Profiles in Pregnant Women After a Gastric Bypass : Findings from Continuous Glucose Monitoring.

BACKGROUND: The diagnosis of gestational diabetes mellitus (GDM) usually requires an oral glucose tolerance test, but this procedure seems inappropriate after gastric bypass surgery (Roux-en-Y gastric bypass (RYGB)) due to specific altered glycemic responses. We aimed here at describing continuous glucose monitoring (CGM) profile of pregnant women after RYGB. METHODS: CGM was performed in 35 consecutive pregnant women after RYGB at 26.2 ± 5 weeks of gestation. RESULTS: After RYGB, pregnant women display high postprandial interstitial glucose (IG) peaks and low IG before and 2 h after meals. The postprandial IG peak is reached early, within 54 ± 9 min. The maximum IG values reach 205 mg/dl, and the percentage of time above 140 mg/dl (6.6 ± 7 %) is similar to what is described in GDM women. CONCLUSIONS: This study is the first to describe CGM profile in pregnant women after RYGB. CGM features are similar to those of non-pregnant post-RYGB patients, characterized by wide and rapid changes in postprandial IG, and high exposure to hyperglycemia. The exposure to hyperglycemia is similar to what is reported in GDM although the time to postprandial peak is shorter. CGM could be an additional useful approach to screen for glucose intolerance during pregnancy after RYGB.

High glycemic variability assessed by continuous glucose monitoring after surgical treatment of obesity by gastric bypass.

BACKGROUND: Obesity surgery elicits complex changes in glucose metabolism that are difficult to observe with discontinuous glucose measurements. We aimed to evaluate glucose variability after gastric bypass by continuous glucose monitoring (CGM) in a real-life setting. METHODS: CGM was performed for 4.2 ± 1.3 days in three groups of 10 subjects each: patients who had undergone gastric bypass and who were referred for postprandial symptoms compatible with mild hypoglycemia, nonoperated diabetes controls, and healthy controls. RESULTS: The maximum interstitial glucose (IG), SD of IG values, and mean amplitude of glucose excursions (MAGE) were significantly higher in operated patients and in diabetes controls than in healthy controls. The time to the postprandial peak IG was significantly shorter in operated patients (42.8 ± 6.0 min) than in diabetes controls (82.2 ± 11.1 min, P = 0.0002), as were the rates of glucose increase to the peak (2.4 ± 1.6 vs. 1.2 ± 0.3 mg/mL/min; P = 0.041). True hypoglycemia (glucose <60 mg/dL) was rare: the symptoms were probably more related to the speed of IG decrease than to the glucose level achieved. Half of the operated patients, mostly those with a diabetes background before surgery, had postprandial glucose concentrations above 200 mg/dL (maximum IG, 306 ± 59 mg/dL), in contrast to the normal glucose concentrations in the fasting state and 2 h postmeal. CONCLUSIONS: Glucose variability is exaggerated after gastric bypass, combining unusually high and early hyperglycemic peaks and rapid IG decreases. This might account for postprandial symptoms mimicking hypoglycemia but often seen without true hypoglycemia. Early postprandial hyperglycemia might be underestimated if glucose measurements are done 2 h postmeal.

Paraganglioma after maternal transmission of a succinate dehydrogenase gene mutation.

CONTEXT: Inactivating mutations of SDHD, which is mapped to 11q23 and encodes the cybS subunit of succinate dehydrogenase, predispose to hereditary paraganglioma (PGL) and/or pheochromocytoma. So far no disease was shown to occur in case of maternal transmission of a SDHD mutation, suggesting the existence of genomic imprinting. A hypothetic model, involving the loss of the maternal copy of a tumor suppressor gene mapped to 11p15 in the tumoral tissue, has been proposed to explain this mode of inheritance. OBJECTIVE: Our objective was to investigate the possibility of maternal transmission of SDHD-linked PGL. DESIGN: A three-generation family carrying the SDHD W43X mutation was studied at the clinical, pathological, and genetical levels. RESULTS: The germline's mutation was probably inherited from the grandfather. In the second generation, three carriers (two females and one male), who had the same at risk 11q13-q23 haplotype, developed multiple cervical PGLs. In the third generation, one boy received the mutation from his mother and developed a glomus tympanicum PGL at 11 yr. He shared only the 11q23 haplotype with the other affected members of the family. Methylation analysis of the differentially methylated region upstream of the maternally expressed H19 gene, mapped to 11p15, showed that the seventh CTCF binding site is hypermethylated in the germline of the affected boy suggesting a gain of imprinting. CONCLUSION: Our data show that maternal transmission of a SDHD-linked PGL, even if a rare event, can occur. Therefore, we propose that children who inherited a pathogenic mutation from their mother should be considered as at risk of PGL.