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 terapêuticoRESUMO
BACKGROUND: Roux-en-Y gastric bypass surgery is widely applied to ameliorate morbid obesity, including diabetes in people with type 2 diabetes. The latter vanish a few days after surgery for many, but not in all patients before any weight reduction has occurred. The explanation for this change in metabolic status is poorly understood, but the observation may suggest that the fate obesity and diabetes is only partly linked after surgery. METHODS: The trajectories of weight reduction measured as reduced body mass index (BMI) in 741obese subjects with and without diabetes were evaluated. Evaluation was performed on three groups: 1) subjects that were non-diabetic before and after surgery; 2) subjects that were diabetics before surgery but non-diabetics after surgery; and 3) subjects that were diabetics before surgery and remained diabetics after surgery. The diabetic state was established at HbA1c above 48 mmol/mol. RESULTS: The trajectories differ significantly between groups and any sub-populations of groups, the latter identified by the distance between individual trajectories using a k-means procedure. The results suggest that different domains in the enormous genetic network governing basic metabolism are perturbed in obesity and diabetes, and in fact some of the patients are affected by two distinct diseases: obesity and diabetes mellitus type 2. CONCLUSION: Although RYGB "normalized" many glycaemic parameters in some of the diabetic subjects apparently converting to a non-diabetics state, other diabetic subjects stay diabetic in the context of the new gut anatomy after surgery. Thus, the obesity part of the glycaemic derangement may have been ameliorated, but some defects of the diabetic state had not.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Derivação Gástrica , Obesidade/complicações , Glicemia , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Obesidade/metabolismo , Obesidade/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production. METHODS: We determined glucose absorption and metabolism and the rate of lipolysis before and 3 months after RYGB in obese glucose-tolerant individuals using the double-tracer technique during a mixed meal. RESULTS: After RYGB, the postprandial plasma glucose profile changed, with a higher peak glucose concentration followed by a faster return to lower than basal levels. These changes were brought about by changes in glucose kinetics: (1) a more rapid appearance of ingested glucose in the systemic circulation, and a concomitant increase in insulin and glucagon-like peptide-1 secretion; (2) postprandial glucose disappearance was maintained at a high rate for a longer time after RYGB. Endogenous glucose production was similar before and after surgery. Postoperative glucagon secretion increased and showed a biphasic response after RYGB. Adipose tissue basal rate of lipolysis was higher after RYGB. CONCLUSIONS/INTERPRETATION: A rapid rate of absorption of ingested glucose into the systemic circulation, followed by increased insulin secretion and glucose disappearance appears to drive the changes in the glucose profile observed after RYGB, while endogenous glucose production remains unchanged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01559792. FUNDING: The study was part of the UNIK program: Food, Fitness & Pharma for Health and Disease (see www.foodfitnesspharma.ku.dk ). Funding was received from the Novo Nordisk foundation and the Strategic Research Counsel for the Capital Area and Danish Research Agency. The primary investigator received a PhD scholarship from the University of Copenhagen, which was one-third funded by Novo Nordisk.
Assuntos
Derivação Gástrica , Absorciometria de Fóton , Índice de Massa Corporal , Feminino , Glucose/metabolismo , Humanos , MasculinoRESUMO
AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones, including GLP-1, is altered. METHODS: Eleven severely obese glucose-tolerant individuals underwent three hyperglycaemic clamps with arginine bolus and co-infusion of either GLP-1, glucose-dependent insulinotropic polypeptide (GIP) or saline before, and at 1 week and 3 months after RYGB. In addition, an OGTT was performed before and 3 months after surgery. RESULTS: After RYGB, insulin sensitivity improved at 1 week and 3 months, while insulin stimulation and glucagon suppression in response to the clamp with saline co-infusion were largely unaltered. The influence of i.v. GLP-1 and GIP on insulin and glucagon secretion was also unchanged postoperatively. In response to the postoperative OGTT at 3 months, insulin and GLP-1, but not GIP, secretion increased. Furthermore, the glucose profile during the OGTT was altered, with a substantial reduction in 2 h plasma glucose and a paradoxical hypersecretion of glucagon. CONCLUSIONS/INTERPRETATION: After RYGB, insulin hypersecretion is linked to the oral, but not the i.v., route of administration and is associated with exaggerated release and preserved insulinotropic action of GLP-1, while both the secretion and action of GIP are unchanged. The results highlight the importance of increased GLP-1 secretion for improving postoperative glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT01559779.
Assuntos
Glicemia/metabolismo , Derivação Gástrica , Polipeptídeo Inibidor Gástrico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Obesidade Mórbida/metabolismo , Pâncreas/metabolismo , Fragmentos de Peptídeos/metabolismo , Adulto , Feminino , Glucagon/metabolismo , Técnica Clamp de Glucose/métodos , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/metabolismo , Resistência à Insulina , Secreção de Insulina , Masculino , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Período Pós-Prandial , Resultado do TratamentoRESUMO
This is a case report of a hospitalised 31-year-old female with rhabdomyolysis following a single 20-minute training session wearing a whole-body electromyostimulation (WB-EMS) suit. The patient presented with severe muscle pain, dark-coloured urine, and among others elevated levels of plasma creatine kinase and myoglobin. This case report demonstrate that unaccustomed WB-EMS training may be harmful. Therefore, healthcare professionals as well as those using and operating the WB-EMS applications should be aware of the potential adverse events to the equipment, e.g. severe rhabdomyolysis.
Assuntos
Terapia por Estimulação Elétrica , Rabdomiólise , Feminino , Humanos , Adulto , Rabdomiólise/etiologia , Rabdomiólise/terapia , Terapia por Estimulação Elétrica/efeitos adversosRESUMO
A 31-year-old woman was admitted to the local department of endocrinology for control of known anti-TPO positive hypothyroidism during pregnancy. The clinician noticed a remarkable hyperpigmentation. Primary adrenal insufficiency was diagnosed and treatment with cortico- and mineralosteroids commenced. Diagnosis of primary adrenal insufficiency during pregnancy is challenging as many symptoms overlap with normal symptoms of pregnancy. The usual diagnostic criteria cannot be used due to the altered hormone concentrations during pregnancy.
Assuntos
Doença de Addison , Hiperpigmentação , Hipotireoidismo , Feminino , Gravidez , Humanos , Adulto , Gestantes , Doença de Addison/complicações , Doença de Addison/diagnóstico , Doença de Addison/tratamento farmacológico , Hospitalização , Hiperpigmentação/diagnóstico , Hiperpigmentação/etiologia , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológicoRESUMO
A 42-year-old man of Chinese descent, known to have Graves' disease, presented with muscle weakness. Neurological examination showed paralysis of the arms and legs, with intact sensory function, while blood-test revealed hypokalaemia and thyrotoxicosis. The neurological symptoms resolved quickly after correction of the serum potassium level. Thyrotoxic periodic paralysis is a rare, reversible complication of hyperthyroidism is characterised by hypokalaemia, hyperthyroidism and paralysis.
Assuntos
Doença de Graves , Hipertireoidismo , Hipopotassemia , Paralisia Periódica Hipopotassêmica , Adulto , Doença de Graves/complicações , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Hipopotassemia/etiologia , Paralisia Periódica Hipopotassêmica/diagnóstico , Perna (Membro) , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Paralisia/etiologia , ParesiaRESUMO
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/cirurgiaRESUMO
BACKGROUND: Weight loss after bariatric surgery varies widely between individuals, partly due to genetic differences. In addition, genetic determinants of abdominal obesity have been shown to attenuate weight loss after dietary intervention with special attention paid to the rs1358980-T risk allele in the VEGFA locus. Here we aimed to test if updated genetic risk scores (GRSs) for adiposity measures and the rs1358980-T risk allele are linked with weight loss following gastric bypass surgery. METHODS: Five hundred seventy six patients with morbid obesity underwent Roux-en-Y gastric bypass. A GRS for BMI and a GRS for waist-hip-ratio adjusted for BMI (proxy for abdominal obesity), respectively, were constructed. All patients were genotyped for the rs1358980-T risk allele. Associations between the genetic determinants and weight loss after bariatric surgery were evaluated. RESULTS: The GRS for BMI was not associated with weight loss (ß = -2.0 kg/100 risk alleles, 95% CI -7.5 to 3.3, p = 0.45). Even though the GRS for abdominal obesity was associated with an attenuated weight loss response adjusted for age, sex and center (ß = -14.6 kg/100 risk alleles, 95% CI -25.4 to -3.8, p = 0.008), it was not significantly associated with weight loss after adjustment for baseline BMI (ß = -7.9 kg/100 risk alleles, 95% CI -17.5 to 1.6, p = 0.11). Similarly, the rs1358980-T risk allele was not significantly associated with weight loss (ß = -0.8 kg/risk allele, 95% CI -2.2 to 0.6, p = 0.25). DISCUSSION: GRSs for adiposity derived from large meta-analyses and the rs1358980-T risk allele in the VEGFA locus did not predict weight loss after gastric bypass surgery. The association between a GRS for abdominal obesity and the response to bariatric surgery may be dependent on the association between the GRS and baseline BMI.
Assuntos
Obesidade Abdominal/genética , Redução de Peso/genética , Adulto , Alelos , Cirurgia Bariátrica , Índice de Massa Corporal , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Relação Cintura-QuadrilRESUMO
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-PrandialRESUMO
Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.
Assuntos
Biomarcadores/urina , Obesidade/urina , Estresse Oxidativo/genética , 8-Hidroxi-2'-Desoxiguanosina/química , Adulto , DNA/isolamento & purificação , DNA/urina , Feminino , Derivação Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/cirurgia , RNA/isolamento & purificação , RNA/urinaRESUMO
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 & derivadosRESUMO
OBJECTIVE: Changes in the secretion of gut-derived peptide hormones have been associated with the metabolic benefits of Roux-en-Y gastric bypass (RYGB) surgery. In this study, the effects of RYGB on anthropometrics, postprandial plasma hormone responses, and mRNA expression in small intestinal mucosa biopsy specimens before and after RYGB were evaluated. METHODS: In a cross-sectional study, 20 individuals with obesity undergoing RYGB underwent mixed meal tests and upper enteroscopy with retrieval of small intestinal mucosa biopsy specimens 3 months before and after surgery. Concentrations of circulating gut and pancreatic hormones during mixed meal tests as well as full mRNA sequencing of biopsy specimens were evaluated. RESULTS: RYGB-induced improvements of body weight and composition, insulin resistance, and circulating cholesterols were accompanied by significant changes in postprandial plasma responses of pancreatic and gut hormones. Global gene expression analysis of biopsy specimens identified 2,437 differentially expressed genes after RYGB, including changes in genes that encode prohormones and G protein-coupled receptors. CONCLUSIONS: RYGB affects the transcription of a wide range of genes, indicating that the observed beneficial metabolic effects of RYGB may rely on a changed expression of several genes in the gut. RYGB-induced changes in the expression of genes encoding signaling peptides and G protein-coupled receptors may disclose new gut-derived treatment targets against obesity and diabetes.
Assuntos
Derivação Gástrica/métodos , Microbioma Gastrointestinal/genética , Expressão Gênica/genética , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The prevalence of metabolically healthy obese (MHO) subjects among morbidly obese subjects is poorly described. AIM: To describe the prevalence of metabolically healthy subjects in a group of morbidly obese referred for bariatric surgery. METHODS: Descriptive cross-sectional study, 1209 subjects (825 women/384 men) mean body mass index (BMI) of 45.6 (range: 35-72.6) kg/m2 and mean age of 42.9 (range: 18-72) years were included. Metabolically unhealthy obese subjects had at least two metabolic risk factors: systolic blood pressure >130 mmHg or diastolic blood pressure >85 mmHg or use of antihypertensive medication, diagnosed diabetes with a HbA1c >6.5% (>48 mmol/mol) or use of antidiabetic medication, high plasma triglycerides or low plasma high-density lipoprotein, or use of lipid-lowering medication. MHO subjects had one or no metabolic risk factors. RESULTS: Thirty-four percent (413/1209) were characterized as MHO subjects. The MHO stage was characterized by female sex, younger age, and lower neck and waist circumferences. The odds ratio of metabolic unhealthy was 1.12 (1.07-1.17, P < 0.001) and 1.02 (1.01-1.04, P < 0002) for every 1 cm increase in neck and waist circumferences, respectively, and 0.94 (0.91-0.97, P < 0.001) for every 1 U increase in BMI and 1.04 (1.03-1.05, P < 0.001) for every 1 year increase in age. CONCLUSIONS: Among severely obese subjects, 34% were classified as having a metabolically healthy state, which was more likely to occur in females, younger individuals and was associated with a lower neck and waist circumferences, younger age, and higher BMI. Whether a group of MHO subjects will remain healthy lifelong is unknown.
Assuntos
Nível de Saúde , Obesidade Mórbida/metabolismo , Adulto , Fatores Etários , Cirurgia Bariátrica , Índice de Massa Corporal , Estudos Transversais , Dinamarca/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pescoço/anatomia & histologia , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Prevalência , Fatores de Risco , Fatores Sexuais , Circunferência da Cintura , Adulto JovemRESUMO
BACKGROUND: The weight loss after bariatric surgery shows considerable individual variation. Twin studies of response to dietary interventions and studies of bariatric surgery patients suggest that genetic differences may play a role. This study aimed to examine the effect of three genetic risk scores on the inter-individual variation in excess body mass index loss (EBMIL) after Roux-en-Y gastric bypass. Furthermore, we searched among known adiposity-related single nucleotide polymorphisms (SNPs) for genetic determinants of the inter-individual variation in EBMIL. METHODS: Patients with morbid obesity underwent Roux-en-Y gastric bypass and were genotyped (n = 577). Two genetic risk scores for weight loss after bariatric surgery and a genetic risk score for body mass index were calculated. Associations between the genetic risk scores and EBMIL were evaluated. Lasso regression was performed on 126 SNPs known to be associated with adiposity. RESULTS: The average EBMIL was 76.9% (range 21.7-149.2%). EBMIL was 81.1% (SD 20.6) and 73.9% (SD 21.7) in the high and low tertile groups of a genetic risk score for weight loss. Patients with a low genetic risk score for body mass index (in the lowest 5% percentile) had an EBMIL of 68.8% (SD 20.6, p = 0.018). Thirteen adiposity-related SNPs were identified to associate with EBMIL through lasso regression. DISCUSSION: A genetic risk score was associated with EBMIL after bariatric surgery, but may not yet be applicable to clinical practice. Patients genetically predisposed to low body mass index had lower weight loss after bariatric surgery.
Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/genética , Obesidade Mórbida/cirurgia , Redução de Peso/genética , Adiposidade/genética , Adulto , Variação Biológica da População/genética , Índice de Massa Corporal , Dinamarca , Feminino , Derivação Gástrica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Resultado do TratamentoRESUMO
CONTEXT: After Roux-en-Y gastric bypass (RYGB) surgery, postprandial plasma glucagon concentrations have been reported to increase. This occurs despite concomitant improved glucose tolerance and increased circulating plasma concentrations of insulin and the glucagon-inhibiting hormone glucagon-like peptide 1 (GLP-1). OBJECTIVE: To investigate whether RYGB-induced hyperglucagonemia may be derived from the gut. DESIGN AND SETTING: Substudy of a prospective cross-sectional study at a university hospital in Copenhagen, Denmark. PARTICIPANTS: Morbidly obese individuals undergoing RYGB (n = 8) with or without type 2 diabetes. INTERVENTIONS: Three months before and after RYGB, participants underwent upper enteroscopy with retrieval of gastrointestinal mucosal biopsy specimens. Mixed-meal tests were performed 1 week and 3 months before and after RYGB. MAIN OUTCOME MEASURES: The 29-amino acid glucagon concentrations in plasma and in mucosal gastrointestinal biopsy specimens were assessed using mass spectrometry-validated immunoassays, and a new monoclonal antibody reacting with immunoreactive glucagon was used for immunohistochemistry. RESULTS: Postprandial plasma concentrations of glucagon after RYGB were increased. Expression of the glucagon gene in the small intestine increased after surgery. Glucagon was identified in the small-intestine biopsy specimens obtained after, but not before, RYGB. Immunohistochemically, mucosal biopsy specimens from the small intestine harbored cells costained for GLP-1 and immunoreactive glucagon. CONCLUSION: Increased concentrations of glucagon were observed in small-intestine biopsy specimens and postprandially in plasma after RYGB. The small intestine harbored cells immunohistochemically costaining for GLP-1 and glucagon-like immunoreactivity after RYGB. Glucagon derived from small-intestine enteroendocrine l cells may contribute to postprandial plasma concentrations of glucagon after RYGB.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Derivação Gástrica/métodos , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucagon/sangue , Insulina/sangue , Intestinos/fisiologia , Obesidade Mórbida/sangue , Adolescente , Adulto , Enteroscopia de Balão , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Polipeptídeo Inibidor Gástrico/sangue , Hemoglobinas Glicadas/análise , Humanos , Masculino , Refeições , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Período Pós-Prandial , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
Roux-en-Y gastric bypass (RYGB) is an efficient treatment for morbid obesity and reduces obesity-related co-morbidities. With the growing number of patients undergoing gastric bypass, complications now demand further attention. Postprandial hyperinsulinemic hypoglycemia (PHH) after Roux-en-Y gastric bypass is a complex condition, characterized by increased glucose variability including both hyperglycemic and hypoglycemic values. PHH seems to be more prevalent than previously suggested and is highly dependent on the choice of diagnostic tool, which has not yet been standardized. Questionnaires, an oral glucose tolerance test, a mixed meal tolerance test, and continuous glucose monitoring have been used, each with their own advantages. The condition is further complicated by a large group of asymptomatic cases. Patients with symptoms of PHH after gastric bypass are characterized by exaggerated insulin and glucagon-like peptide-1 responses compared to asymptomatic operated patients. The counter-regulatory mechanisms responsible for preventing hypoglycemia appear to be altered. The cause of these changes is not entirely understood, and it remains difficult to identify patients at risk of developing hypoglycemia. Known risk factors are female sex, longer time since surgery, and lack of prior diabetes. Management of the hypoglycemic episodes is difficult, and only dietary modifications consisting of frequent and less carbohydrate-rich meals seem to be efficient. Medical treatments and surgical procedures have been attempted in few studies and still warrant further examination.
Assuntos
Derivação Gástrica/efeitos adversos , Hiperinsulinismo/etiologia , Hipoglicemia/etiologia , Obesidade Mórbida/cirurgia , Biomarcadores , Glicemia/metabolismo , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Hiperinsulinismo/diagnóstico , Hiperinsulinismo/terapia , Hipoglicemia/diagnóstico , Hipoglicemia/terapia , Insulina/metabolismo , Masculino , Monitorização Ambulatorial , Obesidade Mórbida/sangue , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Período Pós-Prandial , Fatores de Risco , Fatores SexuaisRESUMO
The combination of gastric bypass, colectomia, lack of substitution with minerals and vitamins, and alcohol consumption led to severe complications in a 57-year-old man. He was submitted to different hospitals 25 times and seen in polyclinics 39 times with no improvement in symptoms of postprandial neurohypoglycaemia, ortostatic hypotension and pronounced hypocalcaemia. The importance of frequent controls after gastric bypass in centres with specialists knowing the common complications after the operation and the need for nutritionel supplements is hereby emphasised.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Derivação Gástrica/efeitos adversos , Hipocalcemia/etiologia , Hipoglicemia/etiologia , Suplementos Nutricionais , Humanos , Hipocalcemia/prevenção & controle , Hipoglicemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Concerns regarding nutritional deficiencies have recently emerged after Roux-en-Y gastric bypass (RYGB). METHODS: A total of 835 subjects underwent RYGB, age 43.3 years, body mass index (BMI) 47.2 kg/m(2). Hematological and calcium metabolic variables were measured before, 6, 12, and 24 months after surgery. Daily supplement of 800 mg calcium, 800 U vitamin D, a multivitamin, and a vitamin B12 injection (1 mg) every third month was recommended. In subjects with low ferritin and decreasing hemoglobin levels, oral, or intravenous iron was administered. RESULTS: Hemoglobin concentration decreased from before surgery to month 24 for both men (9.3 ± 0.05 vs. 8.3 ± 0.08 mmol/L, p < 0.001) and women (8.4 ± 0.03 vs. 7.7 ± 0.06 mmol/L, p < 0.001). At 24 months, anemia was present in 25.8 % of women and 22.1 % of men. Predictors of anemia in both sexes were baseline hemoglobin (p < 0.001), excessive weight loss in men, and younger age in women (p < 0.001). Plasma ferritin levels decreased in both sexes (p < 0.01), whereas concentrations of folic acid and vitamin B12 increased from before surgery to 24 months after surgery (p < 0.001). Vitamin D increased from baseline to month 24 in both sexes (p < 0.01). In women, PTH increased from baseline to month 24 (p < 0.05) with no changes in calcium or magnesium. CONCLUSIONS: Supplementation of calcium and vitamin D was sufficient. Iron substitution did not prevent anemia, which especially affected premenopausal women. More attention should be given to iron substitution after RYGB.
Assuntos
Anemia/diagnóstico , Cálcio/metabolismo , Derivação Gástrica , Obesidade Mórbida/cirurgia , Adulto , Anemia/sangue , Anemia/tratamento farmacológico , Anemia/etiologia , Cálcio/sangue , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/terapia , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/fisiopatologiaRESUMO
AIM: To investigate whether Roux-en-Y gastric bypass surgery (RYGB) - an in vivo model for normalisation of hyperglycaemia - improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: Observational prospective study, 34 obese patients (T2D (n = 14)/IGT (n = 4), and NGT (n = 16)) were investigated before and six and 12months after RYGB. RESULTS: Mean carotid IMT was significantly reduced 12months after RYGB in patients with T2D/IGT (-0.041 mm (95% CI -0.069; -0.012, p = 0.005)) but not in patients with NGT (-0.010 mm (-0.039; 0.020, p = 0.52)). The between-group difference was not significant (p=0.13). Twelve months after RYGB, patients with respectively T2D/IGT and NGT demonstrated changes in weight: -29.9 kg, p<0.001/-30.6 kg, p < 0.001, HbA1c: -0.7%, p < 0.001/-0.1%, p = 0.33, systolic blood pressure: -2 mmHg, p = 0.68/-10 mmHg, p = 0.01 and diastolic blood pressure: -8 mmHg, p = 0.003/-11 mmHg, p < 0.001. 80% of T2D patients terminated antihyperglycaemic medication. CONCLUSION: Mean carotid IMT was significantly reduced 12months after RYGB in patients with T2D/IGT which provides evidence to support that the earliest atherosclerotic changes in the arterial wall are reversible. Although numerically different from the changes observed in patients with NGT, the between-group difference was not statistically significant.