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1.
Surg Obes Relat Dis ; 17(1): 55-63, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33039341

RESUMO

BACKGROUND: Postbariatric hypoglycemia (PBH) is a potentially serious complication after Roux-en-Y gastric bypass (RYGB), and impaired counterregulatory hormone responses have been suggested to contribute to the condition. OBJECTIVES: We evaluated counterregulatory responses during postprandial hypoglycemia in individuals with PBH who underwent RYGB. SETTING: University hospital. METHODS: Eleven women with documented PBH who had RYGB underwent a baseline liquid mixed meal test (MMT) followed by 5 MMTs preceded by treatment with (1) acarbose 50 mg, (2) sitagliptin 100 mg, (3) verapamil 120 mg, (4) liraglutide 1.2 mg, and (5) pasireotide 300 µg. Blood was collected at fixed time intervals. Plasma and serum were analyzed for glucose, insulin, glucagon, epinephrine, norepinephrine, pancreatic polypeptide (PP), and cortisol. RESULTS: During the baseline MMT, participants had nadir blood glucose concentrations of 3.3 ± .2 mmol/L. At the time of nadir glucose, there was a small but significant increase in plasma glucagon. Plasma epinephrine concentrations were not increased at nadir glucose but were significantly elevated by the end of the MMT. There were no changes in norepinephrine, PP, and cortisol concentrations in response to hypoglycemia. After treatment with sitagliptin, 8 individuals had glucose nadirs <3.2 mmol/L (versus 4 individuals at baseline), and significant increases in glucagon, PP, and cortisol responses were observed. CONCLUSIONS: In response to postprandial hypoglycemia, individuals with PBH who underwent RYGB only had minor increases in counterregulatory hormones, while larger hormone responses occurred when glucose levels were lowered during treatment with sitagliptin. The glycemic threshold for counterregulatory activation could be altered in individuals with PBH, possibly explained by recurrent hypoglycemia.


Assuntos
Derivação Gástrica , Hipoglicemia , Obesidade Mórbida , Glicemia , Feminino , Derivação Gástrica/efeitos adversos , Humanos , Hipoglicemia/etiologia , Insulina , Obesidade Mórbida/cirurgia
2.
Obes Surg ; 30(3): 1038-1045, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31907828

RESUMO

BACKGROUND: Early dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention. METHODS: Eleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks, and pasireotide 300 µg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period. RESULTS: During the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4 bpm, p < 0.0001) within 30 min after meal intake, while hypoglycemia occurred in the later postprandial period. The HR increase was accompanied by significant increases in serum albumin, plasma norepinephrine, blood glucose, serum insulin, and plasma GLP-1 concentrations. The postprandial HR changes were positively correlated with the changes in insulin and GLP-1 concentrations. Treatment with acarbose and pasireotide both reduced HR, plasma norepinephrine, and serum insulin, and pasireotide also decreased plasma GLP-1. CONCLUSIONS: RYGB-operated individuals with PBH also have large early postprandial HR increases, hemoconcentration, and sympathetic activation, consistent with early dumping. Moreover, hormone excursions associated with PBH appear to be related to measures of early dumping, suggesting a causal relationship between early dumping and PBH. TRIAL REGISTRATION: NCT02527993.


Assuntos
Derivação Gástrica , Hipoglicemia , Obesidade Mórbida , Glicemia , Feminino , Derivação Gástrica/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon , Humanos , Hipoglicemia/etiologia , Insulina , Obesidade Mórbida/cirurgia , Período Pós-Prandial
3.
Obes Surg ; 30(4): 1605-1610, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31709494

RESUMO

Post-bariatric hypoglycemia (PBH) can be a serious complication after Roux-en-Y gastric bypass (RYGB), and treatment with somatostatin analogs has been suggested. We investigated the acute effects of three different doses of pasireotide (75 µg, 150 µg, and 300 µg) on the postprandial glucose metabolism in five RYGB-operated individuals with PBH using a mixed meal test. All three doses prevented hypoglycemia but were associated with a notable increase in postprandial hyperglycemia. Moreover, all doses greatly diminished insulin, C-peptide, and glucagon-like peptide-1 responses. Considering its strong hyperglycemic potential, we suggest that pasireotide should be administered carefully in RYGB-operated individuals with PBH, and if necessary, a 75 µg dose seems sufficient to prevent hypoglycemia.


Assuntos
Derivação Gástrica , Hipoglicemia , Obesidade Mórbida , Glicemia , Derivação Gástrica/efeitos adversos , Humanos , Hipoglicemia/prevenção & controle , Insulina , Obesidade Mórbida/cirurgia , Somatostatina/análogos & derivados
4.
Diabetes Obes Metab ; 21(9): 2142-2151, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31144430

RESUMO

AIM: To investigate the effects of acarbose, sitagliptin, verapamil, liraglutide and pasireotide on post-bariatric hypoglycaemia (PBH) after Roux-en-Y gastric bypass. MATERIALS AND METHODS: In a randomized crossover study, 11 women who had undergone Roux-en-Y gastric bypass and had documented hypoglycaemia were each evaluated during a baseline period without treatment and during five treatment periods with the following interventions: acarbose 50 mg for 1 week, sitagliptin 100 mg for 1 week, verapamil 120 mg for 1 week, liraglutide 1.2 mg for 3 weeks and pasireotide 300 µg as a single dose. Treatment effects were evaluated by a mixed-meal tolerance test (MMTT) and, for all treatment periods except pasireotide, by 6 days of continuous glucose monitoring (CGM). RESULTS: Treatment with acarbose and treatment with pasireotide both significantly lifted nadir glucose levels (mean ± SEM 3.9 ± 0.2 and 7.9 ± 0.4 vs 3.4 ± 0.2; P < .03) and reduced time in hypoglycaemia during the MMTTs. Acarbose reduced peak glucose levels and time in hyperglycaemia, whereas pasireotide greatly increased both variables. Acarbose and pasireotide reduced insulin and C-peptide levels, and pasireotide also diminished glucagon-like peptide-1 levels. Sitagliptin lowered nadir glucose values, while verapamil and liraglutide had no effect on hypoglycaemia. During the CGM periods, the treatments had no impact on hypoglycaemia, whereas acarbose and liraglutide reduced hyperglycaemia and glycaemic variability. CONCLUSIONS: In an experimental setting, treatment with acarbose and pasireotide reduced PBH. Acarbose appears to have an overall glucose-stabilizing effect, whereas pasireotide leads to increased and sustained hyperglycaemia.


Assuntos
Derivação Gástrica/efeitos adversos , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade Mórbida/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Acarbose/uso terapêutico , Adulto , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia , Estudos Cross-Over , Feminino , Derivação Gástrica/métodos , Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos , Humanos , Hipoglicemia/sangue , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/sangue , Período Pós-Prandial , Fosfato de Sitagliptina/uso terapêutico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Resultado do Tratamento , Verapamil/uso terapêutico
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