The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance.

BACKGROUND: Puberty can affect vitamin D levels. OBJECTIVES: The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance. METHODS: A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013. RESULTS: Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty. CONCLUSION: Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal children.

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain) / Control metabólico y complicaciones crónicas durante un período de 3 años en una cohorte de pacientes diabéticos tipo 2 atendidos en asistencia primaria en la Comunidad de Madrid (España)

BACKGROUND: Our aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain). METHODS: From 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period. RESULTS: A significant decrease in serum glucose levels (143 ± 42 mg/dl vs 137 ± 43 mg/dl, p < 0.00), HbA1c (7.09 ± 1.2% vs 7.02 ± 1.2%, p < 0.00), total cholesterol (191.4 ± 38 mg/dl vs 181.5 ± 36 mg/dl, p < 0.00), LDL cholesterol (114.7 ± 31 mg/dl vs 105.5 ±30 mg/dl, p < 0.00) and triglyceride levels (144.5 ± 93 mg/dl vs 138 ± 84 mg/dl, p < 0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2 ± 14 mg/dl vs 49.9 ± 16 mg/dl, p < 0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%. CONCLUSION: Metabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up

ANTECEDENTES: Nuestro objetivo ha sido analizar el control metabólico y las complicaciones crónicas de pacientes con diabetes mellitus tipo 2 (DM2) que acudían regularmente a consultas de asistencia primaria durante 3 años de seguimiento en la Comunidad de Madrid (España). MÉTODOS: Desde 2007 a 2010, 153 médicos de asistencia primaria de 51 centros de salud familiares incluyeron prospectivamente 3268 pacientes con DM2. Se realizó un estudio de cohorte prospectivo con evaluación anual de la misma población durante 3 años. Se determinaron los objetivos de control y la incidencia de complicaciones crónicas de la diabetes. RESULTADOS: Se comprobaron descensos significativos de los niveles séricos de glucosa (143 ± 42 mg/dl frente a 137 ± 43 mg/dl, p < 0,00), HbA1c (7,09 ± 1,2% frente a 7,02 ± 1,2%, p < 0,00), colesterol total (191,4 ± 38 mg/dl frente a 181,5 ± 36 mg/dl, p < 0,00), colesterol LDL (114,7 ±31 mg/dl frente a 105,5 ± 30 mg/dl, p < 0,00) y triglicéridos (144,5 ± 93 mg/dl frente a 138 ± 84 mg/dl, p < 0,00) durante el período del estudio. Por el contrario, se observó una elevación significativa de los niveles de colesterol HDL (49,2 ± 14 mg/dl frente a 49,9 ± 16 mg/dl, p < 0,00). La incidencia de complicaciones diabéticas durante el período del estudio fue baja: enfermedad coronaria 6,2%, enfermedad arterial periférica 3%, ictus isquémico 2,8%, pie diabético 11,2%, nefropatía 5,9%, retinopatía 4,5% y neuropatía 3%. CONCLUSIÓN: El control metabólico de los pacientes con DM2 atendidos en asistencia primaria en la Comunidad de Madrid durante 3 años era adecuado e iba acompañado de un porcentaje bajo de complicaciones crónicas durante este período de seguimiento

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain).

BACKGROUND: Our aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain). METHODS: From 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period. RESULTS: A significant decrease in serum glucose levels (143±42mg/dl vs 137±43mg/dl, p<0.00), HbA1c (7.09±1.2% vs 7.02±1.2%, p<0.00), total cholesterol (191.4±38mg/dl vs 181.5±36mg/dl, p<0.00), LDL cholesterol (114.7±31mg/dl vs 105.5±30mg/dl, p<0.00) and triglyceride levels (144.5±93mg/dl vs 138±84mg/dl, p<0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2±14mg/dl vs 49.9±16mg/dl, p<0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%. CONCLUSION: Metabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up.

Parenteral nutrition-associated hyperglycemia in non-critically ill inpatients increases the risk of in-hospital mortality (multicenter study).

OBJECTIVE: Hyperglycemia may increase mortality in patients who receive total parenteral nutrition (TPN). However, this has not been well studied in noncritically ill patients (i.e., patients in the nonintensive care unit setting). The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS: This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality. RESULTS: The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47-21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA1c levels. CONCLUSIONS: Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality.

Fe de errores de «Estudio descriptivo de la evolución clínico-asistencial de la población con diabetes tipo 2 en la Comunidad de Madrid. Estudio de seguimiento diabético tipo 2» / Erratum to “Descriptive study on the outcome of clinical care of the type 2 diabetes population in the Community of Madrid. Type 2 diabetes follow-up (ESD-2)”

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Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty.

The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R(2)=0.10, p<0.05) and leptin levels (R(2)=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.

Insulin action in adipose tissue in type 1 diabetes.

BACKGROUND: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI), and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes. METHODS: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. (125)I-insulin binding and U-[(14)C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject. RESULTS: The duration of disease was negatively correlated with both (125)I-insulin binding capacity (r = -0.70, P < 0.05) and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively). Maximum specific (125)I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01). Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01). No correlation was found between BMI and insulin action. CONCLUSION: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a decrease in insulin action in these patients, and involving both receptor and postreceptor mechanisms.

Estudio descriptivo de la evolución clínico-asistencial de la población con diabetes tipo 2 en la Comunidad de Madrid. Estudio de seguimiento diabético tipo 2 (ESD-2) / Descriptive study on the outcome of clinical care of the type 2 diabetes population in the Community of Madrid. Type 2 diabetes follow-up (ESD-2)

Objetivos. El objetivo del estudio es conocer el grado de control de los factores de riesgo cardiovascular y la prevalencia de complicaciones crónicas de la población con diabetes mellitus tipo 2 (DM2) en la Comunidad de Madrid, en condiciones habituales de práctica asistencial diaria durante 3 años de seguimiento. Materiales y métodos. Para ello, hemos realizado un estudio epidemiológico, transversal y descriptivo, de los pacientes con DM2 seguidos en 51 centros de salud, con la participación de 134 profesionales sanitarios de todas las áreas sanitarias de la Comunidad de Madrid. La muestra se obtuvo mediante muestreo sistemático. Analizamos variables sociodemográficas, biológicas/ bioquímicas, de resultado y de procesos asistenciales. El tratamiento estadístico de los datos se realizó mediante el programa de análisis estadístico SPSS 15.0. Resultados. La muestra de pacientes estudiados estuvo constituida por 3.268 pacientes. El 50,3% eran varones y el 49,7%, mujeres, con una edad media de 68,8 ± 10,9 años, y un tiempo medio de evolución de diabetes mellitus de 7,9 ± 7,4 años y mediana de 6 años. Los resultados de comorbilidad mostraron principalmente que el 70,4% tenía la presión arterial elevada, y el 48,4%, obesidad. La presión arterial sistólica media fue de 131,7 ± 14,5 mmHg, y en el 35,3% de los diabéticos fue menor de 130 mmHg. La presión arterial diastólica media fue de 76,1± 9 mmHg, y en el 51,4% de los pacientes estaba por debajo de los 80 mmHg. El 25,3% tenía una presión arterial sistólica/diastólica por debajo de 130/80 mmHg. Es de destacar la elevada prevalencia de complicaciones macrovasculares con un 18,3%, sin diferencias en la prevalencia de complicaciones crónicas de la diabetes mellitus señaladas por la bibliografía, salvo en la retinopatía con una prevalencia del 8%, probablemente por ser el proceso asistencial de registro más bajo(AU)

Conclusiones. El grado de control integral (hemoglobina glucosilada < 7%, lipoproteínas de baja densidad < 100 y presión arterial < 130/80 mmHg) sólo lo alcanza el 4,5% de la población. En nuestro estudio son evidentes las dificultades de alcanzar un control integral del paciente con DM2(AU)

Aims. To study the level of control of cardiovascular risk factors, and prevalence of chronic complications in type 2 diabetic (T2D) patients in daily practice in the Community of Madrid. Design. An epidemiological cross-sectional study in T2D patients attending 51 general practitioner clinics, with the participation of 134 health professionals from all the health areas in the Madrid Community. The sample was obtained by systematic sampling. Measurements. Sociodemographic, biological/biochemical processes and outcomes of the clinical care were recorded. For the statistical analysis the software SPSS 15.0 was used. Results. A total of 3268 T2D patients were studied, 50.3% men and 49.7% women, mean age 68.8±10.9 years, and with a mean duration of diabetes of 7.9±7.4 years and a median of 6 years. High blood pressure was observed in 70.4% of T2D patients, and 48.4% were obese. Mean systolic blood pressure was 131.7±14.5 mmHg, and 35.3% of patients had a systolic pressure less than 130 mmHg. Mean diastolic pressure was 76.1±9 mmHg, and in 51.4% of the patients it was below 80 mmHg. A systolic/diastolic blood pressure below 130/80 mmHg was found in 25.3% of T2D patients. A high prevalence of macrovascular complications (18.3%) was found in our study. No differences in the prevalence was found for chronic complications of diabetes compared with that previously published, except for retinopathy, with a prevalence of 8% in our study, probably reflecting a low case register. Conclusions. The level of integrated control in T2D (HbA1C < 7%, LDL < 100 and BP < 130/80 mmHg), was only observed in 4.5% of the patients. The study shows the difficulty of achieving integral control of T2D patients(AU)

Plasma kisspeptin levels are elevated in cord blood and present sexual dimorphism in the adult population: relation with leptin, gonadotropins and anthropometrical data.

Kisspeptin, the product of the hypothalamic KISS1 gene, is a main regulator of the hypothalamic-pituitary-gonadal axis and could be a link between metabolism and reproduction through its interaction with leptin. Kisspeptin could be involved in gonadotropin regulation and responsive to leptin levels from the first stages of life, exhibiting, as does leptin, sexual dimorphism. To test our hypothesis, we have analyzed plasma kisspeptin levels and their possible relationship with gonadotropins and leptin in a cohort composed of newborns (n = 86) and adults (n = 55). Plasma kisspeptin, gonadotropin and leptin levels were measured by RIA and multiplexed bead immunoassays, respectively. We have built a multivariate linear regression model (analyzing kisspeptin and LH separately as dependent variables) by stepwise analysis, incorporating the variables that had shown significant correlation in the univariate analysis. Cord blood samples exhibited high kisspeptin levels 127.01(113-141.02 pmol/l), but these were not sexually dimorphic. The adult population exhibited sexual dimorphism (3.72(2.95-4.49) vs. 1.77(1.23-2.31)pmol/l women vs. men, p<0.05). Leptin levels showed sexual dimorphism in cord blood samples and also in the adult population. Furthermore, there was a significant interaction between LH and kisspeptin levels and kisspeptin was negatively correlated with age. The high kisspeptin levels observed in cord blood, with no sexual dimorphism, suggest a placental source. The sexual dimorphism exhibited in adulthood supports the notion that there are different sources and/or differential kisspeptin regulation between men and women.

High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents.

OBJECTIVE: We intend to assess the utility of the high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular risk in obese children and adolescents. METHODS: The study included children and adolescents between 6 and 18 years of age with a body mass index (BMI) higher than 2 SDS. All the patients had their blood pressure taken and hs-CRP, hepatic function, lipid profile and uric acid were determined after 12 h of fasting. Likewise, an oral glucose tolerance test was performed, determining basal glucose and insulin levels, and after stimulus. We considered the presence of metabolic syndrome when the obese children and teenagers showed at least two of the following conditions: decreased high density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, hypertension or alteration in glucose metabolism. RESULTS: Out of the 115 obese children studied, 24% showed signs of metabolic syndrome. Those with metabolic syndrome presented higher levels of hs-CRP (mean: 3.8 mg/l; 95% CI: 2.8-4.8) in comparison with the obese patients who did not show signs of metabolic syndrome (mean: 2 mg/l; 95% CI: 1.5-2.5). After a multivariate analysis, the variables that appear to influence the changes in hs-CRP were BMI, triglycerides and HDL-cholesterol levels. CONCLUSION: The hs-CRP is a useful tool for early diagnosis of cardiovascular risk in obese children and teenagers.

Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot?

Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise in the adrenal medulla and the extra-adrenal paraganglia, respectively. Inheritance of these tumors is mainly a result of mutations affecting the VHL, RET, NF1, and SDH genes. Germ-line mutations of the SDH genes have been found to account for nearly 10% of apparently sporadic cases. Nevertheless, alterations other than point mutations have not yet been well characterized. In this study, we investigated the frequency of gross SDH deletions in 24 patients who tested negative for point mutations and had at least one of the recommended features for genetic testing. For this purpose, we used a technique that is easy to implement in the lab to specifically detect gross deletions affecting SDHB, SDHC, and SDHD. We identified 3 heterozygous SDHB deletions (3/24) in 3 independent cases with paraganglioma: 1 whole SDHB deletion and 2 deletions exclusively affecting exon 1. These latter mutations match the unique gross deletion previously reported, indicating this region could be a hot spot for gross SDHB deletions. It seems likely that these alterations can account for a considerable number of both familial and apparently sporadic paraganglioma cases. Although this is the first report describing the presence of gross deletions in patients with apparently sporadic paragangliomas, the extra-adrenal location of the tumor seems to constitute a determining factor for whether to include these patients in genetic testing for gross deletions in the SDHB gene.

Phosphatidylinositol 3-kinase activation is required for sulfonylurea stimulation of glucose transport in rat skeletal muscle.

Sulfonylureas are drugs widely used in the treatment of patients with type 2 diabetes mellitus. In addition to their pancreatic effect of stimulating insulin secretion, many studies suggest that sulfonylureas also have extrapancreatic actions. We have previously reported that gliclazide, a second-generation sulfonylurea, stimulates the glucose uptake by rat hindquarter skeletal muscle directly and immediately by promoting the translocation of glucose transporter 4 to the plasma membrane. The aim of our study was to approach the gliclazide intracellular signaling pathway. For this purpose, we incubated clamped and isolated soleus muscle from rat with gliclazide. The following results were obtained: 1) gliclazide stimulates insulin receptor substrate (IRS)-1-phosphatidylinositol 3 (PI3)-kinase-associated activity, and this activity is necessary for gliclazide-stimulated glucose transport; 2) gliclazide treatment produces a gradual translocation of the diacylglycerol (DAG)-dependent isoforms protein kinase C (PKC) alpha, theta, and epsilon from cytosolic to membrane fraction that is dependent on PI3-kinase and phospholipase C (PLC)-gamma activation; and 3) PKC and PLC-gamma activation is necessary for gliclazide-stimulated glucose transport. We propose a hypothetical signaling pathway by which gliclazide could stimulate IRS-1 that would allow its association with PI3-kinase, promoting its activation. PI3-kinase products could induce PLC-gamma activation, whose hydrolytic activity could activate the DAG-dependent isoforms PKC alpha, theta, and epsilon.