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Introducción: la diabetes mellitus tipo 2 es una enfermedad crónica que puede causar estrés psicológico en el desarrollo de la enfermedad y como suceso estresante, mientras que la angustia por la diabetes se asocia con estresores como el descontrol de las concentraciones de glucosa, presencia de complicaciones agudas o crónicas, disciplina y apego en el tratamiento integral. El objetivo del estudio fue analizar la literatura científica disponible sobre el estrés psicológico y angustia por diabetes en relación con el con- trol glucémico en adultos con diabetes mellitus tipo 2. Materiales y métodos: para la búsqueda de literatura se utilizaron las bases de datos Pubmed, Medline, Biblioteca Virtual en Salud, CINAHL, EBSCO, Wiley y Google Académico. Se incluyeron artículos indexados en bases de datos con idioma inglés, español y portugués, de diseños descriptivos, correlacionales y experimentales publicados en el periodo 2010-2020. Los artículos se evaluaron a través de la lista de revisión del Joanna Briggs Institute. Resultados: se encontró que el estrés psicológico ocurre mayormente en mujeres y que la angustia por diabetes es predictora del control glucémico pobre, provoca un manejo inadecuado de la glucosa, aumenta la hemoglobina glucosilada y también es una de las causas de mortalidad en hombres. Conclusiones: los hallazgos muestran que existe mayor relación entre la angustia por diabetes y el control glucémico en estos pacientes
Introduction: type 2 diabetes mellitus is a chronic disease that can cause psychological stress in the development of the disease and as a stressful event, while diabetes distress is associated to stressors such as uncontrolled diabetes, presence of acute or chronic complications, discipline and adherence in comprehensive treatment. The aim of the study is to analyze the available scientific literature on psychological stress and diabetes distress in relation to glycemic control in adults with type 2 diabetes mellitus. Materials and methods: For the literature search, Pubmed, Medline, Virtual Health Library, CINAHL, EBSCO, Wiley and Google databases were used. Articles indexed with English, Spanish and Portuguese languages, with descriptive, correlational and experimental designs published in the period 2010 to 2020. The articles were evaluated through the Joanna Briggs Institute Check list. Results: 10 articles that met the inclusion criteria were analyzed, some studies showed an associated of psychological stress and diabetes distress with glycated hemoglobin, in addition, it was found that psychological stress is mostly in women and diabetes distress is a predictor of poor glycemic control, it causes inadequate glucose management, increases glycated hemoglobin and is also one of the causes of mortality in men. Conclusions: The findings show that there is a relationship mainly between diabetes distress and glycemic control in these patients.
Introdução: A diabetes mellitus tipo 2 é uma doença crônica que pode causar estresse psicológico no surgimento da doença e ser um evento estressante, enquanto que a angústia por diabetes está associada a estressores como os níveis glicose descontrolados, presença de complicações agudas ou crônicas, disciplina e aderência a um tratamento integral. O objetivo do estudo foi analisar a literatura científica disponível sobre o estresse psicológico e a angústia por diabetes em relação ao controle glicêmico em adultos com diabetes mellitus tipo 2. Materiais e métodos: As bases de dados Pubmed, Medline, Biblioteca Virtual en Salud, CINAHL, EBSCO, Wiley e Google foram utilizadas para a pesquisa bibliográfica. Foram incluídos artigos indexados em bases de dados em inglês, espanhol e português, com desenhos descritivos, correlacionais e experimentais publicados no período de 2010 a 2020. Os artigos foram avaliados através do Check List do Instituto Joanna Briggs. Resultados: Foram analisados 10 artigos que cumpriram com os critérios de inclusão, alguns estudos mostraram associação do estresse psicológico e angústia por diabetes com a hemoglobina glicosilada, além disso, descobriu-se que o estresse psicológico apresenta principalmente nas mulheres e a angústia por diabetes é um preditor de controle glicêmico deficiente, provocando manejo inadequado da glicose, aumentando a hemoglobina glicosilada e também, é uma das causas de mortalidade nos homens. Conclusões: Os resultados mostraram que existe uma maior relação entre a angustia por diabetes e o controle glicêmico nestes pacientes
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HumanosRESUMEN
Severe insulin resistance can be caused by rare genetic defects in the insulin receptor known as insulin receptoropathies. These genetic defects cause a wide spectrum of clinical manifestations ranging from mild syndromes to lethal disorders. Among those is the HAIR-AN an extreme subtype of polycystic ovary syndrome (PCOS). We present a case of a 29-year-old woman with amenorrhea, severe insulin resistance, hirsutism, and acanthosis nigricans who also developed endometrial cancer. She was found to carry a novel heterozygous nonsense mutation insulin receptor gene (INSR). The mutation was inherited from the mother. Levels of insulin receptor and AKT were measured using Western-Blot from peripheral blood mononuclear cells and were both decreased. Thus, we conclude that the identified mutation in the insulin receptor gene and lead to decreased activity of the downstream signaling of the insulin pathway.
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AIM: To identify Prediabetes (PreD) as early and serious diabetes step using clinical-biochemical characteristics in the population of the Primary Prevention Diabetes Buenos Aires (PPDBA) study. METHODS: PPDBA Study evaluated benefits of adopting healthy lifestyles to prevent T2D. It recruited people 45-75 years of age with PreD (impaired fasting glycaemia [IFG], impaired glucose tolerance [IGT] or both, American Diabetes Association criteria), using an opportunistic approach. They completed a FINDRISC questionnaire, and those with a score ≥13 points were invited to participate. When they accepted, we performed an oral glucose tolerance test (OGTT) with a complete lipid profile and HbA1c while physicians completed a clinical history. We recruited 367 persons, and depending on OGTT results, the sample was divided into normals (NGT), PreD, or with diabetes (last one was excluded in our analysis). Data were statistically analyzed using parametric and nonparametric tests and logistic regression to identify parameters associated with PreD. RESULTS: From the recruited (n = 367) 47.7% have NGT, 48.5% PreD and 3.8% unknown T2D (excluded). People with PreD were significantly older, with a higher percentage of overweight/obesity, BMI, and larger waist circumference than NGT. They also showed significantly higher fasting and 2 h post glucose load, HbA1c, and triglyceride levels. No significant differences were recorded in the blood pressure, lipid profile though both groups had abnormally high LDL-c values. They also had a larger percentage of TG/HDL-c ratios (insulin resistance indicator) (55% vs. 37.5%). Logistic regression analysis showed that PreD was significant associated with age, waist circumference, and triglyceride above target values. CONCLUSION: Our findings showed that clinical and biochemical parameters were significantly different between people with PreD and those with NGT. This evidence supports the concept that PreD is a serious dysfunction, which should be early diagnosed and treated properly to prevent its transition to T2D and its complications.
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Diabetes Mellitus Tipo 2 , Intolerancia a la Glucosa , Resistencia a la Insulina , Estado Prediabético , Humanos , Estado Prediabético/epidemiología , Hemoglobina Glucada , Glucemia/análisis , Triglicéridos , Diagnóstico Precoz , AyunoRESUMEN
PURPOSE: To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR - ) GIPR. METHODS: Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). RESULTS: A total of 74 patients (54% female) were included. Eighteen tumors (24%) were GIPR + . Gsp mutation was detected in 30 tumors (40%). GIPR + tumors were more frequently densely granulated adenomas (83% vs 47%, p = 0.028). There was no difference in clinical, biochemical, radiological, therapeutic (surgical cure or response to medical therapy), or other pathological features between GIPR + and GIPR - tumors. Twenty-eight out of 56 (50%) GIPR - tumors harbored a gsp mutation, whereas two out of 18 (11%) GIPR + tumors harbored a gsp mutation (p = 0.005). CONCLUSION: We described, for the first time, that GIPR + and gsp mutations are not mutually exclusive, but gsp mutations are less common in GIPR + tumors. GIPR + and GIPR - tumors have similar clinical, biochemical, radiological, therapeutic, and pathological features, with the exception of a high frequency of densely granulated adenomas among GIPR + tumors.
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Receptores de la Hormona Gastrointestinal , Humanos , Femenino , Masculino , Receptores de la Hormona Gastrointestinal/genética , Mutación , Anticuerpos Monoclonales , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
In recent years, bile acids (BA) have received great interest due to their pleiotropic biological activity and the presence of plasma membrane-bound and nuclear receptors. Moreover, BA in blood have been identified by metabolite screening approaches as biomarkers that are associated with various diseases and even with a human longevity phenotype. With the growing interest in the microbiota contribution to the health-disease trajectory, BA that undergo deconjugation and other modifications by bacteria in the large intestine have become a prime target as a microbiome diversity modifier. We here profiled BA by a quantitative and a semiquantitative approach in 15 healthy and phenotypically very similar young individuals for over a 36-h fasting period, an oral glucose tolerance test (OGTT), and an oral lipid tolerance test (OLTT). We demonstrate a remarkable heterogeneity of the responses and describe the different dynamics of the plasma changes that likely originate from different routes by which BA enters the peripheral blood, and that may represent a direct secretion from the liver into the blood and a route that reaches the blood as a spill-over after passing from the gallbladder through the intestine and the portal system. We discuss the finding that an individual transport process involved in the passage of BA could be a critical determinant in the kinetics of plasma appearance and the overall phenotypic variability found.
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A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia-which would have been missed with traditional binary diagnostic methods-enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.
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AIMS: To evaluate arterial stiffness indicators in people with prediabetes (PreD) and its possible pathogenesis. MATERIALS AND METHODS: Pulse wave velocity (PWV) was measured in 208 people with FINDRISC ≥ 13 (57 ± 8 years old, 68.7% women) and thereafter divided into those having either normal glucose tolerance (NGT) or PreD. In each subgroup we also identified those with/out insulin resistance (IR) measured by the triglyceride/HDL-c ratio (normal cut off values previously established in our population). Clinical and metabolic data were collected for all participants. PWV was compared between subgroups using independent t test. RESULTS: Women and men had comparable clinical and metabolic characteristics with obesity (BMI ≥ 30) and antihypertensive-statin treatment, almost half with either NGT or PreD. Whereas 48% of NGT people presented IR (abnormally high TG/HDL-c ratio), 52% had PreD. PWV was significantly higher only in those with a complete picture of metabolic syndrome (MS). CONCLUSIONS: Since PWV was significantly impaired in people with a complete picture of MS, clinicians must carefully search for early diagnosis of this condition and prescribe a healthy life-style to prevent development/progression of CVD. This proactive attitude would provide a cost-effective preventive strategy to avoid CVD's negative impact on patients' quality of life and on health systems due to their higher care costs.
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El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.
Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.
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Humanos , Resistencia a la Insulina , Prueba de Tolerancia a la Glucosa/métodos , Pronóstico , Curva ROC , HomeostasisRESUMEN
Existing mathematical models for the glucose-insulin (G-I) dynamics often involve variables that are not susceptible to direct measurement. Standard clinical tests for measuring G-I levels for diagnosing potential diseases are simple and relatively cheap, but seldom give enough information to allow the identification of model parameters within the range in which they have a biological meaning, thus generating a gap between mathematical modeling and any possible physiological explanation or clinical interpretation. In the present work, we present a synthetic mathematical model to represent the G-I dynamics in an Oral Glucose Tolerance Test (OGTT), which involves for the first time for OGTT-related models, Delay Differential Equations. Our model can represent the radically different behaviors observed in a studied cohort of 407 normoglycemic patients (the largest analyzed so far in parameter fitting experiments), all masked under the current threshold-based normality criteria. We also propose a novel approach to solve the parameter fitting inverse problem, involving the clustering of different G-I profiles, a simulation-based exploration of the feasible set, and the construction of an information function which reshapes it, based on the clinical records, experimental uncertainties, and physiological criteria. This method allowed an individual-wise recognition of the parameters of our model using small size OGTT data (5 measurements) directly, without modifying the routine procedures or requiring particular clinical setups. Therefore, our methodology can be easily applied to gain parametric insights to complement the existing tools for the diagnosis of G-I dysregulations. We tested the parameter stability and sensitivity for individual subjects, and an empirical relationship between such indexes and curve shapes was spotted. Since different G-I profiles, under the light of our model, are related to different physiological mechanisms, the present method offers a tool for personally-oriented diagnosis and treatment and to better define new health criteria.
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Epidemiological studies indicate an inverse association of coffee consumption with risk of type 2 diabetes mellitus. However, studies to determine the clinical effects of coffee consumption on the glucose metabolism biomarkers remain uncertain. The aim of this systematic review was to evaluate the effects of coffee consumption on glucose metabolism. A search of electronic databases (PubMed and Web of Science) was performed identifying studies published until September 2017. Eight clinical trials (nâ¯=â¯247 subjects) were identified for analyses. Participants and studies characteristics, main findings, and study quality (Jadad Score) were reported. Short-term (1-3â¯h) and long-term (2-16 weeks) studies were summarized separately. Short-term studies showed that consumption of caffeinated coffee may increase the area under the curve for glucose response, while for long-term studies, caffeinated coffee may improve the glycaemic metabolism by reducing the glucose curve and increasing the insulin response. The findings suggest that consumption of caffeinated coffee may lead to unfavourable acute effects; however, an improvement on glucose metabolism was found on long-term follow-up.
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Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.
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Adiposidad/efectos de los fármacos , Suplementos Dietéticos , Secreción de Insulina/efectos de los fármacos , Vitamina D/farmacología , Vitaminas/farmacología , Animales , Hipotálamo/metabolismo , RatasRESUMEN
OBJECTIVES: The fructosamine test is used in the monitoring of diabetes mellitus, particularly in cases with restrictions on the use of glycated hemoglobin (mainly in the setting of altered red blood cell lifespan and interference by hemoglobin variants). It could also provide additional information on shorter-term glycemic control. The objective of the study is to establish the reference range of the fructosamine in the Brazilian population. DESIGN AND METHODS: The reference interval was defined as suggested by the Clinical and Laboratory Standards Institute (CLSI). The study participants were from a Brazilian cohort (The Longitudinal Study of Adult Health - ELSA-Brasil) with baseline data collected between 2008 and 2010. A total of 466 subjects were selected after exclusion of diabetic individuals, and those with altered glycemic markers and renal function tests. RESULTS: The reference interval was 186-248⯵mol/L for women and 196-269⯵mol/L for men. Fructosamine levels were higher in men than in women (pâ¯=â¯0.006) and in the non-white population (pâ¯=â¯0.034) and had a negative correlation with the body mass index (râ¯=â¯-0.117; pâ¯=â¯0.011). CONCLUSIONS: The reference intervals for fructosamine were affected by sex. Reference intervals stratified by sex would be more adequate in the interpretation of the fructosamine test.
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The present study evaluated the effects of maternal dyslipidaemia on blood pressure (BP), cardiorespiratory physiology and biochemical parameters in male offspring. Wistar rat dams were fed either a control (CTL) or a dyslipidaemic (DLP) diet during pregnancy and lactation. After weaning, both CTL and DLP offspring received standard diet. On the 30th and 90th day of life, blood samples were collected for metabolic analyses. Direct measurements of BP, respiratory frequency (RF), tidal volume (VT) and ventilation (VE) under baseline condition, as well as during hypercapnia (7 % CO2) and hypoxia (KCN, 0·04 %), were recorded from awake 90-d-old male offspring. DLP dams exhibited raised serum levels of total cholesterol (TC) (4·0-fold), TAG (2·0-fold), VLDL+LDL (7·7-fold) and reduced HDL-cholesterol (2·4-fold), insulin resistance and hepatic steatosis at the end of lactation. At 30 d of age, the DLP offspring showed an increase in the serum levels of TC (P<0·05) and VLDL+LDL (P<0·05) in comparison with CTL offspring. At 90 d of age, DLP offspring exhibited higher mean arterial pressure (MAP, approximately 34 %). In the spectral analysis, the DLP group showed augmented low-frequency (LF) power and LF:high-frequency (HF) ratio when compared with CTL offspring. In addition, the DLP animals showed a larger delta variation in arterial pressure after administration of the ganglionic blocker (P=0·0003). We also found that cardiorespiratory response to hypercapnia and hypoxia was augmented in DLP offspring. In conclusion, the present data show that maternal dyslipidaemia alters cardiorespiratory physiology and may be a predisposing factor for hypertension at adulthood.
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Sistema Cardiovascular/fisiopatología , Dislipidemias/sangre , Fenómenos Fisiologicos Nutricionales Maternos , Efectos Tardíos de la Exposición Prenatal , Sistema Respiratorio/fisiopatología , Animales , Presión Sanguínea , Colesterol/sangre , Hígado Graso/fisiopatología , Femenino , Hipertensión/fisiopatología , Resistencia a la Insulina , Masculino , Embarazo , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
ABSTRACT Objective Our goal was to investigate which glucose measurement from the 75-g oral glucose tolerance test (OGTT) has more capability of predicting large for-gestational-age (LGA) newborns of mothers with gestational diabetes mellitus (GDM). Subjects and methods The study group consisted of 118 consecutively pregnant women with singleton pregnancy, patients of Outpatients Department of the Endocrinology, Diabetes, and Metabolic Disorders Clinic. All were prospectively screened for GDM between 24th and 28th week of pregnancy and followed to delivery. Outcome measures included: patients’ ages, pre-pregnancy BMI, BMI before delivery, FPG, 1 and 2 hour OGTT glucose values, haemoglobin A1c at third trimester, gestational week of delivery, mode of delivery and baby birth weight. Results From 118 pregnancies, 78 (66.1%) women were with GDM, and 40 (33.9%) without GDM. There were statistically significant differences (30.7 versus 5.0%, p < 0.01) between LGA newborns from GDM and control group, respectively. Gestation week of delivery and fasting glucose levels were independent predictors for LGA (Beta = 0.58 and Beta = 0.37 respectively, p < 0.01). Areas under the receiver operator characteristic curve (AUC) were compared for the prediction of LGA (0.782 (0.685-0.861) for fasting, 0.719 (0.607-0.815) for 1-hour and 0.51 (0.392-0.626) for 2-hour OGTT plasma glucose levels). Conclusion Fasting and 1-hour plasma glucose levels from OGTT may predict LGA babies in GDM pregnancies.
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Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Glucemia/análisis , Diabetes Gestacional/metabolismo , Macrosomía Fetal/diagnóstico , Edad Gestacional , Prueba de Tolerancia a la Glucosa/métodos , Peso al Nacer , Índice de Masa Corporal , Tamaño Corporal/fisiología , Diabetes Gestacional/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Curva ROCRESUMEN
OBJECTIVES: To evaluate (a) the prevalence of cystic fibrosis-related diabetes mellitus (CFRD) in a non-Caucasian population treated in a University Hospital in São Paulo, Brazil; and (b) if annual screening of patients with cystic fibrosis (CF) ≥ 10 yr of age, with oral glucose tolerance test (OGTT), resulted in early detection of CFRD. SUBJECTS AND METHODS: A cross-sectional study was performed with retrospective/prospective analysis of CF patients ≥10 yr of age. Various parameters were analyzed. Patients previously diagnosed with CFRD had their parameters collected at the time of diabetes diagnosis; others were submitted to annual OGTTs, with the parameters collected at the time of their last OGTT. RESULTS: A total of 60 subjects [29 females/31 males; mean age 19.1 yr (±7.6)] were analyzed. In our group of CF patients, we found that 30% had CFRD, 26.7% had altered response to OGTT, and 43.3% had normal glucose tolerance. Analysis of those patients with CFRD showed that the mean age at the time of diagnosis of CFRD, in patients diagnosed by OGTT screening, was 13.5 yr (±2.9) vs. 22.3 yr (±5.4) among those previously diagnosed by clinical suspicion (p < 0.001). CONCLUSIONS: The prevalence of CFRD in our patients is high, similar to the data from Caucasian populations, and significantly higher than previously reported in Brazil. Screening with OGTT resulted in earlier diagnosis of CFRD by 8 yr. These data may help convince national CF centers that CFRD is frequent, and that screening should be mandatory.
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Fibrosis Quística/fisiopatología , Diabetes Mellitus Tipo 1/diagnóstico , Adolescente , Adulto , Brasil/epidemiología , Niño , Estudios Transversales , Fibrosis Quística/sangre , Fibrosis Quística/microbiología , Fibrosis Quística/terapia , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/etiología , Diagnóstico Precoz , Femenino , Prueba de Tolerancia a la Glucosa , Hospitales Universitarios , Humanos , Masculino , Servicio Ambulatorio en Hospital , Prevalencia , Estudios Prospectivos , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/fisiopatología , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/fisiopatología , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Higher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group. METHODS: A prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n=10) and South Asian (n=8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated. RESULTS: Age (Caucasians (CAU) 21.5±0.7 years vs South Asians (SA) 21.4±0.7 years (mean±SEM)) and body mass index (CAU 22.7±0.7 kg/m(2) vs SA 22.1±0.8 kg/m(2)) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851±99.8 mmol/l vs SA 1235±155.0 mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed. CONCLUSION: Healthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.
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Pueblo Asiatico , Péptido 1 Similar al Glucagón/sangre , Insulina/sangre , Población Blanca , Adulto , Área Bajo la Curva , Glucemia/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Masculino , Valores de Referencia , SurinameRESUMEN
In this paper we used a mathematical model to explore the effects of impaired ATP production and glucose sensitivity on the electrical response and insulin secretion of human β-cells. The model was extended by the addition of explicit empirical equations that describe recent experimental observations, namely, the increase of ATP as a function of glucose concentration and the oscillations in ATP at high glucose levels. Simulations were performed at selected glucose concentrations from an oral glucose tolerance test in normal subjects to evaluate the response of the human β-cell in normal and pathological scenarios. Our simulations reproduced experimental observations, such as the impaired insulin secretion as a consequence of β-cell dysfunction and restoration of electrical activity by the use of a sulfonylurea. Our results suggest that both reduced glucose sensitivity and impaired ATP production could be related to the pathogenesis of type 2 diabetes.
En este artículo usamos un modelo matemático para explorar los efectos de alteraciones en la producción de ATP y sensibilidad a la glucosa en la respuesta eléctrica y la secreción de insulina en células β humanas. El modelo fue extendido al añadir ecuaciones empíricas explícitas que describen recientes observaciones experimentales, como el incremento en el ATP como función de la concentración de glucosa y las oscilaciones en el ATP a altos niveles de glucosa. Se realizaron simulaciones a niveles de glucosa alcanzados durante una prueba de tolerancia a la glucosa para evaluar la respuesta de la célula β humana en escenarios normales y patológicos. Nuestras simulaciones reprodujeron varias observaciones experimentales, tales como la secreción de insulina alterada como consecuencia de la disfunción de la célula β y la restauración de la actividad eléctrica al aplicar una sulfonilurea. Nuestros resultados sugieren que tanto una reducción en la sensibilidad a la glucosa como la alteración en la producción de ATP podrían estar relacionadas a la patogénesis de la diabetes tipo 2.
RESUMEN
BACKGROUND: The insertion/deletion polymorphism in the gene encoding the angiotensin-converting enzyme (ACE I/D) was associated with arterial hypertension and obesity in adults, but the data in children are scarce and yielded contrasting results. We assessed the impact of the ACE I/D on blood pressure and obesity related traits in a Brazilian cohort of obese children and adolescents. METHODS AND RESULTS: ACE I/D was genotyped in 320 obese children and adolescents (64% of girls) aged 7-16years, referred for a weight-loss program. We observed an association of the D-allele with blood pressure and with pre-hypertension/hypertension in boys (odds ratio 2.44, 95% C.I. 1.34-4.68, p=0.005 for a codominant model). The D-allele, insulin resistance and body fat mass had independent and additive effects and explained 14% of the variance of pre-hypertension/hypertension. The BMI, waist circumference, and body fat mass were significantly higher in DD/ID boys than in II boys (p<0.005). Allelic associations with obesity related traits were independent of the association with blood pressure. No genotype associations were observed in girls. CONCLUSIONS: The D-allele of the ACE I/D polymorphism was associated with arterial hypertension and with obesity related traits in boys, but not in girls, in a cohort of obese children and adolescents. These associations were independent of each other, as well as of the effects of other confounding traits such as insulin secretion, insulin sensitivity and glucose tolerance. Our results are in agreement with experimental evidences suggesting that the renin-angiotensin system plays a role in the regulation of visceral adipose tissue accumulation.
Asunto(s)
Adiposidad/genética , Hipertensión/genética , Mutación INDEL , Obesidad/genética , Peptidil-Dipeptidasa A/genética , Adolescente , Presión Arterial/genética , Niño , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipertensión/enzimología , Grasa Intraabdominal/enzimología , Grasa Intraabdominal/patología , Masculino , Obesidad/enzimología , Obesidad/fisiopatología , Polimorfismo GenéticoRESUMEN
OBJECTIVES: To assess the association of weight loss and insulin sensitivity, glucose tolerance, and metabolic syndrome (MS) in obese adolescents following weight loss treatment, and to determine the threshold amount of weight loss required to observe improvements in these measures. STUDY DESIGN: A randomized, controlled behavioral weight loss trial was conducted with 113 obese adolescents. Changes in fasting insulin, homeostasis model assessment of insulin resistance, whole body insulin sensitivity index (WBISI), body mass index (BMI), and MS criteria were assessed at baseline and at month 4. RESULTS: There was significant improvement in all measures of insulin sensitivity at month 4. Mean fasting insulin dropped from 22.3 to 16.6 µU/mL (P < .0001). Homeostasis model assessment of insulin resistance decreased significantly from 4.9 to 3.7 (P = .001) and WBISI increased significantly from 2.87 to 3.98 (P < .0001). An 8% reduction in BMI led to a significant improvement in WBISI (P = .03) and was the optimal threshold. Fewer individuals met criteria for MS after weight loss (P = .0038), although there were no significant changes in the individual features of the syndrome. CONCLUSIONS: In this trial, weight loss at month 4 was associated with improved insulin sensitivity in obese adolescents. An approximate decrease in BMI of 8% was the threshold level at which insulin sensitivity improved. As more weight loss programs are designed for obese adolescents, it will be important to have reasonable weight loss goals that will yield improvements in metabolic and cardiovascular disease risk factors.