Caracterización del metabolismo óseo mineral en pacientes con enfermedad renal crónica en hemodiálisis en el Servicio de Salud Metropolitano Sur, Santiago de Chile / Bone mineral metabolism in patients with chronic kidney disease on dialysis in Southern Metropolitan Santiago

Background: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a condition of dialysis patients associated with both morbidity and mortality. Management is based on clinical guidelines with goals that are hard to comply with. Aim: To describe and compare biochemical variables associated with this disorder in two different time periods. Material and Methods: Revision of medical records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48% females), dialyzed during 2012 in Southern Metropolitan Santiago. Information about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was retrieved. Results: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml respectively (p < 0.05). The figures for serum calcium corrected by albumin were 9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7 and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4 and 42.5 mg²/dl² (p < 0.05). Of note, the proportion patients with serum calcium below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to 2012. The proportion of patients with biochemical variables within recommended ranges was lower in 2012 than in 2009. Conclusions: There was a low proportion of patients with bone metabolism parameters within ranges recommended by clinical guidelines. These parameters were worst in 2012.

Glutathione: Glutathione Sulfide Redox Imbalance in Early Impaired Fasting Glucose.

Aim: The current study aims to examine the balance between glutathione and glutathione sulfide and how this was disturbed in patients with impaired fasting glucose (IFG) level. The study also included 8-hydroxy-2’-deoxyguanosine to provide a more comprehensive picture of the overall redox state. Methodology: A cross-sectional analysis of ninety medication free participants without reported history of cardiovascular disease and/or diabetes mellitus was undertaken with data collected from the Diabetes Complications Research Initiative database at Charles Sturt University. Fasting blood glucose, HbA1c and cholesterol as standard markers for diabetes mellitus and associated complications were measured in addition to the emerging biomarkers glutathione (GSH), glutathione disulfide (GSSG), and urinary 8- hydroxy-2’-deoxyguanosine (8OHdG). Results: The IFG group had a mean blood glucose level above 6.1mmol/L being significantly higher compared to control (P<0.001). Traditional clinical markers were all within the normal range for both groups. However the GSH/GSSG ratio (8.53±5.4 vs 6.62±2.2, P=.04) was significantly lower in the IFG group. GSH and 8OHdG, being markers for oxidative stress, were not significantly different between the two groups. Conclusion: The free radical related changes in metabolic redox pathways are linked to oxidative stress and related pathologies but may not be associated with disease progression, providing an explanation why conflicting results are presented in the literature concerning any individual biomarkers and risk of diabetes. Our study included individuals with no medication use and mild hyperglycemia (impaired fasting glucose) and indicates a pro-oxidant response to mild-moderate hyperglycemia with a moderate rise in oxidative DNA damage.

A link between sleep loss, glucose metabolism and adipokines

The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH) secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

Hepatitis C y diabetes mellitus tipo 2: un estudio prospectivo / Hepatitis C and type 2 diabetes mellitus: a prospective study

Se ha establecido una relación epidemiológica entre hepatitis C crónica (HCV) Y Diabetes Mellitus tipo 2. El objetivo del presente estudio fue determinar de forma prospectiva la prevalencia de Diabetes Mellitus(DM) e intolerancia a la Glucosa en ayunas (IGA) en pacientes con hepatitis C crónica no tratados o naive, en comparación con la población general y con pacientes con enfermedades hepáticas de diferente etiología. Se incluyo una muestra de 13 pacientes que acudieron a la consulta de la Fundación Zuliana del Hígado desde Enero del año 2008 hasta Diciembre del año 2009 en el estudio. La prevalencia de DM e IGA fue de 38% comparado con 8% de la Población general (Centro Venezolano de información y estadística) y 25% del grupo control de 16 pacientes con enfermedades hepáticas de otras etiologías. De los 13 pacientes, cinco fueron Genotipo 1b, uno genotipo 1a y siete Genotipo 2a. De los pacientes con DM o IGA, dos fueron Genotipo 1b, uno 1a y dos 2a. De los cinco pacientes con DM o IGA cuatro tenían antecedente familiares de Diabetes. En conclusión, pacientes con HCV crónica tienen una mayor prevalencia de DM e IGA en comparación con la población general y con pacientes afectados por enfermedades hepáticas de otra etiología. El Genotipo no tuvo relación en este estudio con la DM o la IGA; los marcadores antropométricos de Obesidad estuvieron asociados en tres de los cinco pacientes lo cual sumado a la historia familiar de Diabetes siguiere una relación multifactorial en la patogénesis de la DM en los pacientes con HCV.

An epidemiologic link between chronic Hepatitis C (HCV) and Type 2 Diabetes mellitus (DM) has been established. The objective of the present study was to prospectively determine the prevalence of Diabetes Mellitus (DM) and impaired fasting glucose (IFG) in patients with hepatitis C not treated or naive, in comparison with the general population and patients with other hepatic diseases. A sample of 13 patients who went to the outpatient clinic of the Zuliana Foundation of the Liver, from January of year 2008 to December of year 2009 was included in the study. The prevalence of DM and IGA was of 38% compared with 8% of the general Population (Center Venezuelan of information and statistic) and 25% of the group control of 16 patients with other hepatic diseases. Of 13 patients five were Genotype 1b, one genotype 1a and seven Genotype 2a. Of the patients with DM or IGA, two were Genotype 1b, one 1a and two 2a. Of the five patients with DM or IGA four had family history of Diabetes. In conclusion, patients with chronic HCV have a greater prevalence of DM and IGA in comparison with the general population and patients affected by different hepatics diseases. There was not relation in this study between the Genotype with the DM or the IGA; the anthropomorphic markers of Obesity were associated in three of the five patients, which added to the familiar history of Diabetes will follow a multifactorial relation in the pathogenesis of the DM in the patients with HCV.

Dietary glycemic load, glycemic index, and refined grains intake are associated with reduced beta-cell function in prediabetic Japanese migrants / Associação entre carga glicêmica da dieta, índice glicêmico e consumo de cereais refinados e função reduzida das células-beta em migrantes japoneses com pré-diabetes

Objective: To investigate the association between carbohydrate intakes and β-cell function (HOMA-β) in Japanese-Brazilians with impaired glucose tolerance (IGT). Methods: Dietary intakes were assessed by a validated food frequency questionnaire in a cross-sectional survey carried out in 2000. The associations between diet and HOMA-β were verified in 270 newly diagnosed IGT in multiple linear regression models. Results: The mean (SD) age was 58 (11) years and the mean HOMA-β was 65 (47). The glycemic load was inversely associated with HOMA-β, β1 -0.140 (95%CI = -1.044; -0.078), p = 0.023. The inverse association was also observed for refined grains intakes: -0.186 (95%CI = -0.4862; -0.058), p = 0.012. After adjustments for body mass index, the glycemic index was inversely associated with HOMA-β: -0.1246 (95%CI = -2.2482, -0.0257), p < 0.001. Conclusions: These data suggested that dietary glycemic load, glycemic index, and refined grains intakes are associated with reduced β-cell function, and the quality of dietary carbohydrates may be relevant for maintaining β-cell function among individuals with IGT.

Objetivo: Investigar a associação entre o consumo de carboidratos e função das células-β (HOMA-β) em nipo-brasileiros portadores de tolerância à glicose diminuída (TGD). Métodos: O consumo alimentar habitual foi avaliado por meio do questionário quantitativo de frequência alimentar previamente validado em estudo transversal conduzido em 2000. A associação entredieta e HOMA-β foi verificada em 270 indivíduos portadores de TGD em modelos de regressão logística ajustados. Resultados: A média (DP) de idade foi 58 (11) anos e do HOMA-β foi 65 (47). A carga glicêmica foi inversamente associada ao HOMA-β, β1 -0.140 (95%CI = -1.044; -0.078), p = 0,023. Associação inversa com o consumo de cereais refinados também foi observada: -0.186 (95%CI = -0.4862; -0.058), p = 0,012. Após ajuste pelo índice de massa corpórea, foi verificada a associação inversa entre índice glicêmico e HOMA-β: -0.1246 (95%CI = -2.2482, -0.0257), p < 0,001. Conclusões: Os dados indicam que a carga glicêmica da dieta, o índice glicêmico e o consumo de cereais refinados estão associados a uma função reduzida das células-β e que aqualidade dos carboidratos da dieta habitual pode ser relevante na manutenção da função de células-β entre indivíduos portadores de TGD.

Características clínicas y metabólicas de los estados de intolerancia a la glucosa y glicemia de ayuno alteradas / Clinical and metabolic features of subjects with glucose intolerance and high fasting glucose levels

Background: Subjects with glucose intolerance or high fasting glucose levels have a higher cardiovascular risk and frequently become diabetic. Aim: Toassess clinical and metabolic characteristics of patients with glucose intolerance or high fasting glucose levels. Material and methods: Fasting and post glucose load serum glucoseand insulin levels were measured in 1404 people, aged 42,0 ± 14,2 years (81% women) with high diabetic risk. We categorized subjects in different alterations of blood glucose, accordingto 2006 American Diabetes Association categories. Insulin resistance (RI), insulin secretion (ß %) and insulin disposition (ID), were calculated using fasting blood glucose and insulin levels, using the homeostasis model assessment (HOMA I and II). Results: Sixty percent of studied subjects had first grade relatives with diabetes mellitus and 1097 (78%) were categorized as normal (N), 45 (3%) as Diabetes Mellitus (DM), 161 (11%) as high fasting glucose levels (GAA) and 103 (7%) as glucose intolerant (ITG). Fifty three of the 106 subjects with GAA (50%), were also glucose intolerant. Subjects with GAA had similar insulinsensitivity and lower ß cell function than N (insulin disposition 58 ± 12 and 111 ± 32%, respectively, p <0.01). ITG had less insulin sensitivity than N (HOMA-IR 2.6 ± 1.50 ± and 2.0 ± 1.30, respectively) and only a mild decrease in ß cell function (insulin disposition 96 ± 26 and 111 ± 32% respectively, p < 0.01). Patients GAA plus ITG had similar alterations than those with DM (HOMA-IR 3.8 ± 2.2 and 4.4 ± 3.7 respectively; insulin disposition 57 ± 10 and 56.0 ± 26% respectively. Conclusions: Patients with higher fasting glucose levels behavedifferently from those with glucose intolerance. High fasting glucose levels are highly prevalent in subjects with high risk of DM and must be considered as risk indicator in preventive programs for diabetes mellitus.

Avaliação da prevalência do diabetes e da hiperglicemia de estresse no infarto agudo do miocárdio / The prevalence of diabetes and stress hyperglycemia in the acute myocardial infarction patients

OBJETIVOS: Determinar a prevalência do diabetes melito (DM) e da hiperglicemia de estresse (HE) em pacientes com infarto agudo do miocárdio (IAM) admitidos em unidade de emergência cardiológica. MÉTODOS: Análise retrospectiva de 2.262 pacientes com IAM, avaliando, além da prevalência de diabetes referido, o diagnosticado e a hiperglicemia de estresse. RESULTADOS: Apesar de referido em 12,1 por cento dos pacientes (H: 10,7 por cento, M: 15,8 por cento), o DM ocorria efetivamente em 24,8 por cento (H: 22,9 por cento, M: 29,7 por cento) e a HE em 13,6 por cento (H: 14,3 por cento, M: 11,7 por cento) dos indivíduos dessa população. Portanto, alterações glicêmicas ocorreram em 37,4 por cento dos indivíduos com IAM (H: 37,2 por cento, M: 41,4 por cento). Nos pacientes com DM, observou-se maior precocidade etária do IAM, maior prevalência de óbitos (DM: 20,7 por cento, ND:13,8 por cento, HE: 13,4 por cento) e de procedimentos cirúrgicos (ND: 33,8 por cento, HE: 18,0 por cento, DM: 21,7 por cento). CONCLUSÃO: A elevada prevalência de DM e hiperglicemia de estresse observada em nosso estudo indica que as alterações glicêmicas constituem um dos mais importantes fatores de risco para o IAM.

OBJECTIVES: To evaluate in our population the real prevalence of diabetes (DM) and stress hyperglycemia (HE) in patients with myocardial infarction (IAM) admitted in a cardiologic emergency unit. METHODS: A retrospective analysis of 2262 patients with AMI evaluating the prevalence of DM (referred and diagnosed) and stress hyperglycemia. RESULTS: Besides 12,1 percent of subjects were previously referred to be diabetic (men: 10.7 percent and women: 15.8 percent), diabetes was effectively diagnosed in 24,8 percent (M: 22,9 percent, W: 29,7 percent) and stress hyperglycemia in 13,6 percent HE of the patients (M: 14,3 percent, W: 11,7 percent) indicating that glycemic alterations were effectively observed in 37.2. percent of the patients with IAM (M: 37,2 percent, W: 41,4 percent). In DM subjects IAM events occurred earlier, total intra-hospital mortality was higher (DM: 20.7 percent, ND: 13,8 percent, HE: 13,4 percent) and less surgical procedures were performed (ND 33.8 percent, DM: 21.7 percent, HE: 18.0 percent). CONCLUSION: The elevated DM and stress hyperglycemia prevalence observed in our study indicates that glycemic alterations is one of the most important risk factors for IAM.

Insulin resistance and hypertension / 华中科技大学学报（医学）（英德文版）

The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance (IR) under the disorder of glucose metabolism and hypertension were studied. By glucose tolerance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucose tolerance curve (AUCG) to area under insulin release curve (AUCI) were calculated and analyzed. The results showed that ISI was decreased to varying degrees in the patients with hypertension, the mildest in the group of NGT with hypertension, followed by the group of IGT without hypertension, the group of IGT with hypertension and DM (P = 0). There was very significant difference in the ratio of AUCG/AUCI between the hypertensive patients with NGT and controls (P = 0). It was concluded that a significant IR existed during the development of IGT both in hypertension and nonhypertension. The increase of total insulin secretion (AUCI) was associated with nonhypertension simultaneously. IR of the hypertensive patients even existed in NGT and was worsened with the deterioration of glucose metabolism disorder, but the AUCI in the HT group changed slightly. A relative deficiency of insulin secretion or dysfunction of beta-cell of islet existed in IGT and DM of the hypertensive patients.

A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 + or - 4 percent (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2) phosphorylation, to 83 + or - 5 percent (P<0.05) in liver and to 77 + or - 4 percent (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding

Incidencia de intolerancia a los carbohidratos en pacientes de la consulta externa: estudio clínico prospectivo / Carbohydrate intolerance: its frequency in patients who attend to the out-patient care unit. Prospective trial

En este estudio se evaluaron a 117 pacientes sin diagnóstico previo de alguna enfermedad que alterara el metabolismo de los carbohidratos, a los que se aplicó una encuesta conteniendo diversos factores de riesgo y se realizaron las siguientes mediciones: talla, peso, circunferencia de cintura y cadera, presión arterial. Se les clasificó en tres grupos según el número de puntos de la encuesta: bajo 0-5, mediano 6-10 y alto riesgo más de 11 puntos. Por último, se les practicó una curva de tolerancia oral a la glucosa (CTOG). El 17.9 por ciento (20) correspondió al sexo masculino mientras que el 82.9 por ciento (97) correspondió al sexo femenino. El antecedente de riesgo más importante para diabetes mellitus fue tener un familiar de 1º y 2º grado, tener más de 40 años, no realizar ejercicio regularmente, tener un índice de masa corporal > 27, multiparidad e índice cintura cadera > 0.84. La incidencia de intolerancia a los carbohidratos fue de 23.9 por ciento, con diabetes mellitus 8.5 por ciento y 67.5 por ciento de individuos normales. Se observó que a los individuos ubicados en los grupos de mediano y alto riesgo según la encuesta es necesario considerar la realización de la CTOG. La glucosa plasmática en ayunas no fue el examen de escrutinio ideal. Se recomienda la aplicación de la encuesta como método de detección temprana, así como la CTOG como método de escrutinio después de la encuesta

Monosodium glutamate (MSG) - obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been descrebed in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/Kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age. At 3 months, the IVGTT was performed by injecting glucose (0.75 g/Kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU. Kg(-1). min (-1) of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups. After the glucose load, increased values of glycemia (p<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasm insulin levels were 39.9 + 4 muU/ml in control and 66.4 + 5.3 muU/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111 percent higher in MSG-obese than in control rats. When insulinemia was clamped, at 102 or 133 muU/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 + 0.8 mg. kg (-1). min(-1) for control rats while 2.1 + 0.3 mg. kg(-1). min(-1) was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg. min. dl(-1), was 13.7 + 2.3 vs 3.3 + 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.

Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus.

Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.