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1.
Diabetologia ; 61(8): 1829-1837, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29732475

RESUMO

AIMS/HYPOTHESIS: Incretin effect-the potentiation of glucose-stimulated insulin release induced by the oral vs the i.v. route-is impaired in dysglycaemic states. Despite evidence from human islet studies that NEFA interfere with incretin function, little information is available about the effect in humans. We tested the impact of acute bidirectional NEFA manipulation on the incretin effect in humans. METHODS: Thirteen individuals with type 2 diabetes and ten non-diabetic volunteers had a 3 h OGTT, and, a week later, an i.v. isoglycaemic glucose infusion (ISO; OGTT matched). Both pairs of studies were repeated during an exogenous lipid infusion in the non-diabetic volunteers, and following acipimox administration (to inhibit lipolysis) in people with diabetes. Mathematical modelling of insulin secretion dynamics assessed total insulin secretion (TIS), beta cell glucose sensitivity (ß-GS), glucose-induced potentiation (PGLU) and incretin-induced potentiation (PINCR); the oral glucose sensitivity index was used to estimate insulin sensitivity. RESULTS: Lipid infusion increased TIS (from 61 [interquartile range 26] to 78 [31] nmol/m2 on OGTT and from 29 nmol/m2 [26] to 57 nmol/m2 [30] on ISO) and induced insulin resistance. PINCR decreased from 1.6 [1.1] to 1.3 [0.1] (p < 0.05). ß-GS, PGLU and glucagon, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) responses were unaffected. Acipimox (lowering NEFA by ~55%) reduced plasma glucose and TIS and enhanced insulin sensitivity, but did not change ß-GS, PINCR, PGLU or glucagon, GLP-1 or GIP responses. As the per cent difference, incretin effect was decreased in non-diabetic participants and unchanged in those with diabetes. CONCLUSIONS/INTERPRETATION: Raising NEFA selectively impairs incretin effect and insulin sensitivity in non-diabetic individuals, while acute NEFA reduction lowers plasma glucose and enhances insulin sensitivity in people with diabetes but does not correct the impaired incretin-induced potentiation.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Insulina/metabolismo , Adolescente , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 2/patologia , Polipeptídeo Inibidor Gástrico/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Teste de Tolerância a Glucose , Humanos , Incretinas/metabolismo , Células Secretoras de Insulina/metabolismo , Lipídeos/química , Pessoa de Meia-Idade , Pirazinas/farmacologia , Fatores de Tempo , Adulto Jovem
2.
Endocr Res ; 43(2): 73-79, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29083246

RESUMO

OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic. METHODS: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers. RESULTS: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 µIU/mL and mean BMI 26.2 ± 3.3 kg/m2. Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205). CONCLUSION: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.


Assuntos
Resistência à Insulina , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/sangue , Tiroxina/efeitos adversos , Adulto , Estudos Transversais , Feminino , Técnica Clamp de Glucose , Humanos , Tireotropina/efeitos dos fármacos
3.
Head Neck ; 37(1): 97-102, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24339184

RESUMO

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) usually emerges as a set of signs and symptoms that, either alone or in combination with standard treatment, may lead to malnutrition and weight loss. METHODS: This study evaluated patients with SCCHN before day 0 and 30 days after the end of treatment, with/without tumor resection. Each individual patient underwent analyses of body composition and resting metabolic rate, as well as assessment of serum glucose, insulin, leptin, adiponectin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), IL-1ß, and insulin sensitivity. RESULTS: There was body mass loss during treatment and significant reduction in body fat and free fat mass. Early nutritional monitoring and tumor resection before treatment led to a better nutritional status and reduced inflammatory state. CONCLUSION: Early nutritional monitoring and resection of the tumor by surgery may be important factors for patients to better tolerate treatment.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Adiponectina/sangue , Adulto , Idoso , Glicemia/metabolismo , Composição Corporal , Índice de Massa Corporal , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Nível de Saúde , Humanos , Insulina/sangue , Resistência à Insulina , Interleucina-1beta/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fator de Necrose Tumoral alfa/sangue
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