Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.

PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. RESULTS: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. CONCLUSIONS: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

BACKGROUND: The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. METHODS: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. RESULTS: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ±â€¯3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. CONCLUSIONS: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD.

Olive oil has a beneficial effect on impaired glucose regulation and other cardiometabolic risk factors. Di@bet.es study.

BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.

Mediterranean diet adherence in individuals with prediabetes and unknown diabetes: the Di@bet.es Study.

BACKGROUND AND AIMS: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). METHODS: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. RESULTS: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. CONCLUSIONS: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.

Establishing cut-off values for apolipoprotein B and non-HDL-C according to LDL-C values in a South European population.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) remains the primary target of therapy in most strategies of dyslipidaemia management focused on cardiovascular disease prevention. Different guidelines have identified specific LDL-C cut-off points as targets for therapeutic intervention. Many clinical situations characterised by dyslipidaemia and elevated triglycerides are common in our environment and in overall industrialised countries. Thus, lipid goals based only on LDL-C could misclassify an important percentage of subjects. The objective of the present study was to establish cut-off point values for apoB and non-HDL-C in relation to the identified LDL-C cut-off points for cardiovascular risk in a South European population. METHODS: We performed a cross-sectional study including 1501 subjects (770 women and 731 men) between 18 and 80 years of age. Samples were collected after 12-14 h of fasting. Cholesterol, HDL-C, triglycerides and apoB levels were measured using direct methods. LDL-C was calculated by the Friedewald formula. Non-HDL-C was calculated as total cholesterol minus HDL-C. RESULTS: The Spearman's rank correlations between apoB and LDL-C (r 0.86, p < 0.0001), and between apoB and non-HDL-C (r 0.91, p < 0.0001) were both significant. The proposed cut-off points for apoB, according to LDL-C goals (70, 100, 130 and 160 mg/dl) in our population are 70, 80, 100 and 115 mg/dl respectively. The proposed cut-off values for non-HDL-C are 100, 120, 150 and 190 mg/dl respectively. CONCLUSION: The established LDL-C cut-off values could not be accurate to estimate cardiovascular risk in subjects with mild hypertriglyceridaemia, as frequently occurs in our Mediterranean population. To take into consideration the burden of atherogenic particles and better classify patients at risk we propose cut-off values for apoB or the equivalent for non-HDL-C. Prospective trials including cardiovascular variables are needed to validate our assumption.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study).

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Iodine intake in the adult population. Di@bet.es study.

BACKGROUND & AIMS: To date no nation-wide study has yet been undertaken in Spain to estimate the iodine deficiency. The aim was to evaluate iodine intake and its conditioning factors in a representative sample of the whole adult population. METHODS: The Di@bet.es Study is a national, cross-sectional, population-based survey conducted in 2009-2010 in Spain. RESULTS: The median urinary iodine (UI) was 117.2 µg/L. Iodized salt (IS) was consumed by 43.9% of the population. The median UI in those who consumed IS and in those who did not consume IS was 131.1 and 110.8 µg/L respectively (p<0.0001). The likelihood of having UI levels above 100 µg/L was significantly associated with the intake of IS (OR=1.47) and milk at least once a day (OR=1.22). Within each individual autonomous communities, the median UI levels in those who consumed IS correlated significantly with the median levels of those who did not consume IS (r=0.76, p=0.001). CONCLUSIONS: Though strictly speaking, Spain should be considered within the category of a country having an adequate iodine intake, the current value is too close to the cut point and does not guarantee that those groups with a greater need for iodine will have the required intake of iodine.

AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia.

Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia. Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined. Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39 ± 8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02 ± 6.20 mM*h/L) (P < 0.05). Postprandial lipemia was similar for the different C573T polymorphisms. Conclusion. The 1166-C allele of the AT1R gene seems to be associated with increased postprandial lipemia. These data confirm the earlier described relationships between the renin-angiotensin axis and triglyceride metabolism.

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study.

AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

Cardiovascular and metabolic risk in outpatients with schizoaffective disorder treated with antipsychotics: results from the CLAMORS study.

AIM: To assess the coronary heart disease (CHD) risk and prevalence of the metabolic syndrome (MS) in patients with schizoaffective disorder (SD) receiving antipsychotics. METHODS: Patients meeting DSM-IV criteria for SD and receiving antipsychotic treatment were recruited in a retrospective, cross-sectional, multicenter study (the CLAMORS study). MS was defined as at least three of the following components: waist circumference greater than 102 cm (men)/greater than 88 cm (women); serum triglycerides greater or equal to 150 mg/dl; HDL cholesterol less than 40 mg/dl (men)/less than 50 mg/dl (women); blood pressure greater or equal to 130/85 mmHg; fasting blood glucose greater or equal to 110 mg/dl. The 10-year CHD risk was assessed by the Systematic coronary risk evaluation (SCORE) (cardiovascular mortality) and Framingham (any cardiovascular event) functions. Clinical severity was assessed using the PANSS and CGI-S scales. RESULTS: A total of 268 valuable patients with SD (127 men, 48.1%), 41.9±12.3 years (mean±S.D.), were analyzed. The 10-year overall cardiovascular mortality and CV-event risk were 0.8±1.6 (SCORE) and 6.5±6.8 (Framingham), respectively. A high/very high risk of any CV event (Framingham≥10%) was associated with severity [CGI-S=3-4; OR: 4.32 (1.15-16.26), P=0.03)]. MS was present in 26.5% (95%CI: 21.2-31.8) of subjects, without gender differences, but significantly associated with patient's impression of severity: CGI=3-4; OR=1.90 (0.83-4.36), and CGI=5-7; OR=3.13 (1.06-9.24), P=0<0.001, and age [OR=1.91 (1.09-3.34), P<0.024)]. CONCLUSIONS: CHD risk and MS prevalence were high among patients with SD, being MS prevalence associated with age and severity of disease.

Obstrucción intestinal aguda por bezoar en un paciente diabético tipo 2 con neuropatía / Acute intestinal obstruction caused by bezoar in a patient with type 2 diabetes and neuropathy

Un bezoar es una masa o concreción de material ingerido que se acumula en el estómago, desde donde puede pasar al resto del tracto intestinal. Son poco frecuentes, siendo el más común el fitobezoar. Éste se ha relacionado con la cirugía gástrica y con procesos que alteran la motilidad intestinal, como la gastroparesia diabética o la neuropatía alcohólica. En la mayoría de los casos se descubren de forma casual, y más raramente por la presencia de complicaciones asociadas. Presentamos el caso de un paciente con antecedentes de diabetes tipo 2 e ingesta crónica de alcohol, que presentó un cuadro obstructivo intestinal agudo causado por dos bezoares(AU)

A bezoar is a mass or concretion of ingested material which accumulates in the stomach, from it can progress into the rest of gastrointestinal tract. Bezoars are unusual, being the phytobezoar the most common. Phytobezoar shave been associated with gastric surgery and other pathologies that can alter intestinal motility, as diabetes gastroparesis or alcoholic neuropathy. In most cases they are found incidentally or, more rarely, they are discovered by associated complications. We report the case of a patient with type 2 diabetes and chronic alcoholism that presented an acute intestinal obstruction caused by two bezoars(AU)

Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis.

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options.

Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes mellitus.

BACKGROUND: To examine the association of biochemical markers of risk (plasma Hcy, microalbuminuria, lipoprotein (a)(Lp(a)) and diabetic dyslipidaemia) with the prevalence of diabetic foot ulceration in type 2 diabetic patients. METHODS: Case/control study conducted in 198 type 2 diabetic patients. 89 patients have foot ulcers and 109 have no foot ulcers (control group), in order to establish ORs for diabetic foot ulceration. In all subjects plasma Hcy, Lp(a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, HbA(1c) and microalbuminuria were measured using standard procedures. RESULTS: Plasma Hcy, microalbuminuria, HbA(1c) and apolipoprotein B levels were significantly higher in patients with foot ulceration compared with the control group. Plasma lipids, Lp(a), vitamin B12 and folic acid values were similar in both groups. In the logistic regression model, plasma Hcy (OR 1.09; 95% CI 1.04-1.69), microalbuminuria (OR 1,01; 95% CI 1.01-1.17) and HbA(1c) levels (OR 1.33; 95% CI 1.04-1.69) were independent risk factors for the presence of diabetic foot ulceration. CONCLUSIONS: In our study, for each micromol increase in plasma Hcy levels there was a 10% increase in the risk of diabetic foot ulceration. In addition, plasma homocysteine, HbA(1c) and microalbuminuria accounted for 50% prevalence risk of diabetic foot ulceration. Further prospective studies should be conducted to confirm the association of plasma Hcy levels with the risk of foot ulceration.

Increased plasma xanthine oxidase activity is related to nuclear factor kappa beta activation and inflammatory markers in familial combined hyperlipidemia.

BACKGROUND AND AIMS: Xanthine oxidase (XO) has been described as one of the major enzymes producing free radicals in blood. Oxidative stress and inflammatory processes have been implicated in the pathogenesis of endothelial dysfunction and the progression of atherosclerosis but until now, there is little data about the influence of vascular prooxidant systems and inflammation in familial combined hyperlipidemia (FCH). Our goal was to evaluate whether XO activity was altered in FCH and if it was related to the inflammatory process represented by NFkB, IL-6 and hsCRP, and assessing the correlation between XO activity and insulin resistance (IR). METHOD AND RESULTS: 40 Non-related subjects with FCH and 30 control subjects were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose, insulin, uric acid, XO activity, malondialdehyde (MDA), IL-6 and hsCRP in plasma and NFkB activity in circulating mononuclear cells. Patients with FCH showed significantly higher levels of uric acid, XO activity, MDA, NFkB activity, IL-6 and hsCRP than controls. XO activity was independently related to NFkB activity with an odds ratio of 4.082; to IL-6 with an odds ratio of 4.191; and to IR with an odds ratio of 3.830. Furthermore, mean NFkB activity, IL-6 levels, and IR were highest in the highest percentile of XO activity. CONCLUSIONS: Subjects with FCH showed increased XO and NFkB activities and low grade inflammatory markers related to atherosclerosis. XO activity was correlated with higher inflammatory activity and IR. These data could explain, in part, the high cardiovascular disease risk present in these patients.

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

BACKGROUND: Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. MATERIALS AND METHODS: Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. RESULTS: Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75.0 +/- 20.7 vs. 42.7 +/- 16.8 relative luminiscence units) and XO (0.44 +/- 0.13 vs. 0.32 +/- 0.09 mU mL(-1)) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. CONCLUSION: Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients.

Diagnóstico diferencial entre osteomielitis de pie y artropatía de Charcot aguda / Differential diagnosis between foot osteomyelitis and acute Charcot arthropathy

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Tratamiento farmacológico de la dislipemia en la diabetes mellitus tipo 2 / Drug treatment of dyslipidemia in type 2 diabetes mellitus

La diabetes mellitus tipo 2 conlleva un elevado riesgo cardiovascular. Un componente significativo de este riesgo puede atribuirse a ladislipemia diabética, un agrupamiento de anomalías de los lípidos y las lipoproteínas en el plasma íntimamente relacionadas. Sus principales características son hipertrigliceridemia, descenso del colesterol ligado a lipoproteínas de alta densidad (cHDL) y aumento de las lipoproteínas de baja densidad (LDL) pequeñas y densas. Estas alteraciones se conocen también como la tríada aterogénica. Otros componentes son la elevación de la apolipoproteína (apo) B, la prolongación de la lipemia posprandialy el aumento de las partículas remanentes, ricas en triglicéridos. En los últimos años, numerosos estudios prospectivos han demostrado los beneficios de las estatinas para mejorar el perfil lipídico de la dislipemiadiabética y también para reducir el riesgo cardiovascular de estos pacientes. Las estatinas se consideran el tratamiento fundamental y básico de la dislipemia diabética. Los fibratos pueden usarse en algunos grupos reducidos de pacientes y, generalmente, siempre en combinación con las estatinas. Estudios futuros con nuevos fármacos hipolipemiantesy antidiabéticos permitirán un tratamiento más eficaz de la dislipemiadiabética (AU)

Type 2 diabetes carries an elevated cardiovascular risk. A significant component of this risk can be attributed to diabeticdyslipidemia, a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The main characteristics of diabetic dyslipidemia are elevated triglycerides, lowered high-densitylipoproteins (HDL) and raised small, denselow-density lipoproteins (LDL). These alterations are also known as the “atherogenic lipid triad”. Other components of the atherogenic lipid profile are elevatedapo B levels, prolonged postprandial lipemia and accumulation of triglyceride-richremnant particles in the circulation. In the last few years, several prospective trials have proven the effectiveness of statins in improving diabetic dyslipidemia and in reducing cardiovascular risk. These drugs are therefore considered the initial drug ofchoice for diabetic dyslipidemia. Fibrates can be used in a subset of patients, mostlyin combination with statins. Future trials with new lipid-lowering and antidiabetic agents will hopefully allow more targeted treatment of lipid disorders and postprandiallipemia in type 2 diabetics (AU)

Dificultad en el tratamiento del hipertiroidismo por amiodarona. Presentación de un caso / Difficult treatment of amiodarone-induced thyrotoxicosis: a case report

La amiodarona puede alterar la función tiroidea en un 15-20% de los pacientes que la toman, dando lugar a hipotiroidismo o hipertiroidismo. La sobrecarga de yodo y la toxicidad directa sobre el tiroides inducida por amiodarona pueden provocar hipertiroidismo. Describimos un caso de tirotoxicosis grave por amiodarona que se diagnosticó buscando la causa que descompensó la cardiopatía de base del paciente, condicionando ésta el pronóstico y el manejo terapéutico. El tratamiento precisó un estrecho seguimiento y se basó en dosis elevadas de propiltiouracilo y dexametasona que no controlaron las consecuencias del hipertiroidismo a nivel cardiaco necesitando la tiroidectomia total. Creemos, con la experiencia aportada, que en determinados casos la cirugía es una opción que debería ser planteada con más precocidad

Amiodarone causes changes in thyroid function tests in about 15-20% of patients, inducing either hypothyroidism or thyrotoxicosis. The iodine load and the destructive thyroiditis caused by amiodarone produce thyrotoxicosis. We report a case of amiodarone-induced thyrotoxicosis diagnosed when investigating the reason for worsening of cardiac funtion. Prognosis and treatment of cardiac disorder were determined by thyrotoxicosis. The management needed a closed monitoring of thryroid function. Treatment was based on high doses of propylthiouracil and dexametasone, but they couldn´t control cardiac condition and surgery was warranted. When amiodarone-induced thyrotoxicosis is refractory to medical treatment, we belive surgery should be considered earlier

Mastopatía diabética en una mujer con diabetes mellitus tipo 1 de larga evolución: descripción de una entidad poco conocida / Diabetic mastopathy in a woman with long-standing type 1 diabetes: a description of a poorly characterized entity

La mastopatía diabética es una forma poco frecuente de mastitis linfocitaria que aparece preferentemente en mujeres con una diabetes mellitus tipo 1 (DM1) de larga evolución. Esta entidad, con una característica proliferación fibrosa del estroma, se encuadra dentro de las lesiones mamarias fibrosas benignas, pero clínicamente puede confundirse con lesiones malignas. En este caso clínico se describe un proceso de mastopatía diabética en una paciente con DM1 de larga duración y complicaciones crónicas microvasculares conocidas, aunque controladas. Tras la detección de la lesión en una ecografía de control, fue remitida al cirujano de mama para su valoración. El diagnóstico se realizó mediante biopsia, y se descartó la presencia de lesiones malignas. El tratamiento de la mastopatía diabética fue conservador

Diabetic mastopathy is an uncommon form of lymphocytic mastitis that typically occurs in women with long-standing type 1 diabetes. This entity, which presents with a characteristic stromal fibrosis, is a benign fibrous lesion, but may clinically mimic a malignant lesion. The authors report a case involving the development of diabetic mastopathy, diagnosed in a woman with long-standing type 1 diabetes and known controlled chronic microvascular complications. After the detection of a breast lump in a routine ultrasound scan, she was referred to a breast surgeon for evaluation. The diagnosis of diabetic mastopathy was confirmed by biopsy, which ruled out the presence of malignant lesions. The management was conservative

Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARalpha-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARalpha to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.