Prevalence of hypoglycaemia in a random population after Roux-en-Y gastric bypass after a meal test.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinaemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. DESIGN: This is a cross-sectional study of patients 4 years after primary RYGB. METHODS: From a total population of 550 patients, a random sample of 44 patients completed the total test procedures. A standardized mixed meal was used as stimulus. Venous blood samples were collected at baseline, every 10 min during the first half hour and every 30 min until 210 min after the start. Symptoms were assessed by questionnaires. Hypoglycaemia is defined as a blood glucose level below 3.3 mmol/L. RESULTS: The prevalence of postprandial hypoglycaemia was 48% and was asymptomatic in all patients. Development of hypoglycaemia was more frequent in patients with lower weight at surgery (P = 0.045), with higher weight loss after surgery (P = 0.011), and with higher insulin sensitivity calculated by the homeostasis model assessment indexes (HOMA2-IR, P = 0.014) and enhanced beta cell function (insulinogenic index at 20 min, P = 0.001). CONCLUSION: In a randomly selected population 4 years after primary RYGB surgery, 48% of patients developed a hypoglycaemic event during an MMTT without symptoms, suggesting the presence of hypoglycaemia unawareness in these patients. The findings in this study suggest that the pathophysiology of PHH is multifactorial.

Prevalence and pathophysiology of early dumping in patients after primary Roux-en-Y gastric bypass during a mixed-meal tolerance test.

BACKGROUND: Early dumping is a poorly defined and incompletely understood complication after Roux-en-Y gastric (RYGB). OBJECTIVE: We performed a mixed-meal tolerance test in patients after RYGB to address the prevalence of early dumping and to gain further insight into its pathophysiology. SETTING: The study was conducted in a regional hospital in the northern part of the Netherlands. METHODS: From a random sample of patients who underwent primary RYGB between 2008 and 2011, 46 patients completed the mixed-meal tolerance test. The dumping severity score for early dumping was assessed every 30 minutes. A sum score at 30 or 60 minutes of ≥5 and an incremental score of ≥3 points were defined as indicating a high suspicion of early dumping. Blood samples were collected at baseline, every 10 minutes during the first half hour, and at 60 minutes after the start. RESULTS: The prevalence of a high suspicion of early dumping was 26%. No differences were seen for absolute hematocrit value, inactive glucagon-like peptide-1, and vasoactive intestinal peptide between patients with or without early dumping. Patients at high suspicion of early dumping had higher levels of active glucagon-like peptide-1 and peptide YY. CONCLUSION: The prevalence of complaints at high suspicion of early dumping in a random population of patients after RYGB is 26% in response to a mixed-meal tolerance test. Postprandial increases in both glucagon-like peptide-1 and peptide YY are associated with symptoms of early dumping, suggesting gut L-cell overactivity in this syndrome.

Satiety and gastrointestinal hormones during a Mixed Meal Tolerance Test after gastric bypass surgery: association with plasma amino acid concentrations.

BACKGROUND: Circulating amino acids have been associated with both appetite and the secretion of anorexigenic hormones in healthy and obese populations. This effect has not been investigated in subjects having undergone Roux-en-Y gastric bypass surgery (RYGB). OBJECTIVE: To investigate the association between postprandial plasma concentrations of amino acids and the anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY), the orexigenic hormone ghrelin, and satiety and hunger in post-RYGB subjects. SETTING: A Dutch surgical department. METHODS: Participants after primary RYGB were studied during a Mixed Meal Tolerance Test (MMTT). Satiety and hunger were assessed every 30 minutes on visual analogue scales. Blood samples were collected at baseline, every 10 minutes during the first half hour and every 30 minutes until 210 minutes after the start. The samples were assessed for 24 amino acids and 3 gastrointestinal hormones. Incremental areas under the curve (iAUCs) were calculated. Exploratory analyses were performed in which subjects were divided into high and low responders depending on the median iAUC. RESULTS: 42 subjects, aged 48 ± 11 (mean ± SD) years, 31 to 76 months post-RYGB and with total weight loss of 30 ± 9% completed the MMTT. Subjects with high satiety scores had more than a 25% higher net iAUC of PYY and GLP-1 and at least a 10% higher net iAUC of 10 amino acids compared to subjects with low scores (P < 0.05). The net iAUC of five of these amino acids (i.e. arginine, asparagine, histidine, serine and threonine) was more than 10% higher in subjects with high responses on GLP-1 and/or PYY (P < 0.05). CONCLUSIONS: Certain postprandial amino acids were associated with satiety and anorexigenic hormones and could therefore play a role in appetite regulation after RYGB; either by a direct effect on satiety, indirectly through gastrointestinal hormones, or both.

Archaeal and bacterial SecD and SecF homologs exhibit striking structural and functional conservation.

The majority of secretory proteins are translocated into and across hydrophobic membranes via the universally conserved Sec pore. Accessory proteins, including the SecDF-YajC Escherichia coli membrane complex, are required for efficient protein secretion. E. coli SecDF-YajC has been proposed to be involved in the membrane cycling of SecA, the cytoplasmic bacterial translocation ATPase, and in the stabilizing of SecG, a subunit of the Sec pore. While there are no identified archaeal homologs of either SecA or SecG, many archaea possess homologs of SecD and SecF. Here, we present the first study that addresses the function of archaeal SecD and SecF homologs. We show that the SecD and SecF components in the model archaeon Haloferax volcanii form a cytoplasmic membrane complex in the native host. Furthermore, as in E. coli, an H. volcanii deltasecFD mutant strain exhibits both severe cold sensitivity and a Sec-specific protein translocation defect. Taken together, these results demonstrate significant functional conservation among the prokaryotic SecD and SecF homologs despite the distinct composition of their translocation machineries.