The association of circulating bioenergetic metabolites with healthy human aging.

Aging is an inevitable and gradual decline in several biological functions. Mitochondrial dysfunction is one of the most important hallmarks of aging. In this context, alterations in metabolites associated with mitochondrial dysfunction may serve as a significant biomarker. This study aimed to investigate the existence of a relationship between the key metabolites involved in bioenergetics metabolism and aging. 53 volunteers ranged 20-85 years participated in the study. We tested the association between different tricarboxylic acid (TCA) cycle metabolites, fatty acid metabolism, and amino acid metabolism with age, sex, body composition, and proxy markers of aging such as walking speed, grip strength and chair test. We found that lactic acid negatively correlated with age while several fatty acid metabolites, such as azelaic, sebacic, and linoleic acids, showed positive correlations with age (p < 0.05). Sex-specific trends, such as glycerol, and dodecanoic acid, were also observed for certain metabolites. Furthermore, citric acid levels were found to have a significant association with physical function and body composition measures. Participants with higher citric acid levels displayed improved performance in physical tests and favorable body composition indices. Additionally, fumaric acid and adipic acid showed positive correlations with fat-free body mass, while sebacic acid was negatively associated with measures of fat mass. These findings underscore the importance of understanding the role of circulating bioenergetics metabolites with age, sex variations, and their potential implications in body composition and physical performance.

Thyroid as a target of adjuvant autoimmunity/inflammatory syndrome due to mRNA-based SARS-CoV2 vaccination: from Graves' disease to silent thyroiditis.

BACKGROUND: As COVID-19 became a pandemic, the urgent need to find an effective treatment vaccine has been a major objective. Vaccines contain adjuvants which are not exempt from adverse effects and can trigger the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). There is very little information about autoimmune endocrine disease and the ASIA after the use of mRNA-based SARS-CoV2 vaccination. CASE SERIES: We report three cases and also review the literature showing that the thyroid gland can be involved in the ASIA induced by the mRNA-based SARS-CoV2 vaccination. We present the first case to date of silent thyroiditis described in the context of SARS-CoV2 vaccination with Pfizer/BioNTech. Also, we discuss the first subacute thyroiditis in the context of SARS-CoV2 vaccination with the Moderna's vaccine. Finally, we provide another case to be added to existing evidence on Graves' disease occurring post-vaccination with the Pfizer/BioNTech vaccine. DISCUSSION: Adjuvants play an important role in vaccines. Their ability to increase the immunogenicity of the active ingredient is necessary to achieve the desired immune response. Both the Moderna and the Pfizer/BioNTech vaccines use mRNA coding for the SARS-CoV2 S protein enhanced by adjuvants. In addition, the cross-reactivity between SARS-CoV2 and thyroid antigens has been reported. This would explain, at least, some of the autoimmune/inflammatory reactions produced during and after SARS-CoV2 infection and vaccination. CONCLUSION: The autoimmune/inflammatory syndrome induced by adjuvants involving the thyroid could be an adverse effect of SARS-CoV2 vaccination and could be underdiagnosed.

Differences in the cluster of depressive symptoms between subjects with type 2 diabetes and individuals with a major depressive disorder and without diabetes.

BACKGROUND: Depressive disorder encompasses a wide spectrum of somatic and psychological symptoms. It is not known whether there are differences regarding the cluster of depressive symptomatology between subjects with depression with and without T2DM. PURPOSE: To explore whether the cluster of depression that prevails among depressive subjects with T2DM differs from individuals with depression, but without T2DM. METHODS: 87 T2DM patients with a pathological Beck Depression Inventory test (BDI) were compared with 50 age- and gender-matched individuals with a major depressive disorder. All 21 items expressed in the BDI were compared between the two groups. RESULTS: The score obtained after administering the BDI was comparable between patients with T2DM and significant depressive symptoms and the control group (18.8 ± 2.7 vs 18.9 ± 3.4; p = 0.9). Subjects with T2DM had higher scores compared with the control group in the following items: sadness (1.4 ± 0.9 vs 0.9 ± 0.9; p = 0.011), difficulty in concentration (1.3 ± 0.8 vs 0.8 ± 0.8; p = 0.01), indecisiveness (1.1 ± 0.8 vs 0.5 ± 0.9; p = 0.012), worries about their health (1.3 ± 0.9 vs 0.6 ± 0.9; p < 0.0001), fatigue (1.2 ± 0.6 vs 0.8 ± 0.7; p = 0.003) and loss of sexual appetite (2.7 ± 0.6 vs 1.2 ± 1.3; p = 0.0001). Suicidal ideation was significantly lower among subjects with T2DM compared with the control group (0.1 ± 0.3 vs 0.6 ± 0.8; p = 0.0001). CONCLUSIONS: Subjects with T2DM and a positive screening for depression presented a different cluster of depression compared with depressed subjects without T2DM, with a predominance of somatic-biological depressive symptoms rather than psychological-cognitive cluster and negative emotions, such as suicidal ideation.

Prevalence and Clinical Correlators of Undiagnosed Significant Depressive Symptoms Among Individuals with Type 2 Diabetes In A Mediterranean Population.

Objective: To determine the frequency and clinical parameters, of clinically significant depressive symptoms among a type 2 diabetes (T2DM) sample from a Mediterranean area without an established diagnosis of depressive disorder (DD). Methods: 320 subjects with T2DM were recruited randomly from Primary-Care settings and the Endocrine Department from a tertiary center in Mallorca (Spain). 91 healthy individuals matched by age, gender and BMI were used as controls. All participating patients graded by the presence of DD by using the "Beck Depression Inventory" (BDI), considering pathological a cut-off score equal or greater than 16. Results: 27.2% T2DM subjects had significant symptoms of DD compared with 12.1% in the control group (p<0.01). BDI score was higher among T2DM when compared with controls (12±9.6 vs. 7.4±5, p<0.0001). The proportion of females (68% vs. 37%, p<0.0001), subjects without an active job (68% vs. 45%, p=0.01) and singles (38% vs. 18%, p=0.007) was greater among T2DM with a BDI≥16. Subjects with criteria for DD had a higher BMI (31.99±5.96 vs. 30.53±5.62, p=0.03). Fasting plasma glucose was higher among T2DM with a BDI≥16 (162±70 vs. 147±45 mg/dl, p=0.02) as well as HbA1c levels (7.9±1.8% vs. 7.4±1.4%, p=0.01), triglycerides (203±183 vs. 161±103 mg/dl; p=0.03) and LDL-cholesterol (112±31 vs. 104±35 mg/dl; p=0.03). Gender, marital status, BMI and triglycerides were independently related to the presence of DD after a logistic regression model. Conclusions: Relevant depressive symptoms are more prevalent among Mediterranean T2DM subjects than in general population. Main clinical correlators of significant depressive symptoms are gender, marital status and BMI.

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial.

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

[Cardiovascular effects and safety of glucose-lowering drugs: current situation]. / Efectos cardiovasculares y seguridad de los fármacos hipoglucemiantes: situación actual.

Diabetes mellitus is an independent cardiovascular risk factor. Therefore, in addition to normalising blood glucose, the aim of the treatment for diabetes mellitus should be to prevent cardiovascular complications. However, the evidence available on the cardio-protective role of the different glucose-lowering drugs is scarce and poor, particularly as regards with the risk of major cardiovascular events. In this context, the regulatory agencies have modified the regulations for the approval of glucose-lowering drugs, now requiring to demonstrate the glucose-lowering effect together with a robust assessment of the cardiovascular safety. The aim of this work is to review the cardiovascular effects of the different glucose-lowering drugs, focusing on their impact on the risk of major cardiovascular events.

Assessment of risk factors and test performance on malnutrition prevalence at admission using four different screening tools.

BACKGROUND & AIMS: Malnutrition is very common in patients when admitted to the hospital. The aim of the present study was: a) to determine the prevalence of malnutrition at admission in a tertiary care hospital and identify risk factors for malnutrition, and b) to test the sensitivity and specificity of different screening tests for malnutrition compared to subjective global assessment (SGA). METHODS: We conducted a prospective study at 24h of admission in order to assess malnutrition in 537 adult subjects (56.4% males, mean age of 61.3±17.7 years) using 4 different screening tools: mininutritional assessment short form (MNA-SF), nutritional risk screening 2002 (NRS2002), malnutrition universal screening tool (MUST), and SGA. Anthropometrics and co-morbidities were registered. RESULTS: The overall rate of undernutrition was 47.3%. Specific rates were 54.2% in patients > 65y vs. 40.7% < 65y (p = 0.002) and 63.4% in medical vs. 34.0% surgical department (p < 0.001). Identified risk factors of malnutrition at admission were: the presence of heart disease (OR 1.74 CI 95% 1.16-2.60 p = 0.007) for MNASF (AUC 0.62); liver disease (OR 4.45 CI 95% 1.9410.22 p < 0.001), > 65y (OR 2.10 CI 95% 1.19-3.93 p = 0.011), medicine department (OR 3.58 CI 95% 1.93-6.62 p < 0.001) for SGA (AUC 0.96); lung disease (OR 3.34 CI 95% 1.45-7.73 p = 0.005), medicine department (OR 2.55 CI 95%1.09-5.98 p = 0.032) for NRS 2002 (AUC 0.97). Recent unintentional weight loss was a common factor. CONCLUSIONS: Undernourishment at hospital admission is frequent. Comorbidities may contribute to the presence of undernutrition at admission. Nonetheless, SGA, NRS2002, MNA-SF or MUST can be used in our setting.

Antecedentes y objetivos: La desnutrición es muy frecuente en los pacientes que ingresan en el hospital. El objetivo de nuestro estudio es a) determinar la prevalencia de desnutrición al ingreso en un hospital de tercer nivel e identificar los factores de riesgo para desnutrición. b) Estudiar la sensibilidad y especifidad de diferentes test de cribado de desnutrición comparados con las valoración global subjetiva (VGS). Material y métodos: Realizamos un estudio prospectivo a las 24 h del ingreso hospitalario a individuos (56.4% hombres con una edad media de 61,3 ± 17 años) utilizando 4 test de cribado diferentes: mininutritional assessment short form (MNA-SF), nutritional risk screening 2002 (NRS2002), malnutrition universal screening tool (MUST) y VGS. Además, se recogieron medidas antropométricas y comorbilidades. Resultados: La prevalencia global de desnutrición fue de 47.3%. Las tasas específicas fueron 54,2% para > 65 años, 40,7% en < 65 años (p = 0,002), 63,4% en las áreas médicas, 34,0% áreas quirúrgicas (p < 0,001). Los factores que influían en la presencia de desnutrición al ingreso fueron: cardiopatía (OR 1,74 IC 95% 1,16-2,60 p = 0,007) en el MNA-SF (AUC 0,62); hepatopatía (OR 4,45 IC 95% 1.9410,22 p < 0,001), > 65años (OR 2,10 IC 95% 1,19-3,93 p = 0,011), áreas médicas (OR 3,58 IC 95% 1,93-6,62 p < 0,001) en la VGS (AUC 0,96); neumopatía (OR 3,34 IC 95% 1,45-7,73 p = 0,005), áreas médicas (OR 2,55 IC 95% 1,09-5,98 p = 0,032) en el NRS 2002 (AUC 0,97). La pérdida de peso involuntaria fue común a todos los test. Conclusiones: La desnutrición es frecuente al ingreso hospitalario. La presencia de comorbilidades puede influir en la presencia de desnutrición al ingreso, sin embargo, podemos utilizar cualquiera de los tests propuestos para su detección en nuestro hospital.

Mesenteric vein thrombosis after laparoscopic sleeve gastrectomy.

Mesenteric vein thrombosis is a rare complication of bariatric laparoscopic surgery. We report a case of a 47-year-old man with obesity who had mesenteric vein thrombosis 14 days after laparoscopic sleeve gastrectomy. He was treated with heparin anticoagulation with a good therapeutic response. This case and literature review illustrate that mesenteric vein thrombosis has to be included in the differential diagnosis of abdominal pain after a bariatric procedure and listed formally as a complication of bariatric surgery.

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy.

AIMS/HYPOTHESIS: Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine whether a decrease in IRBP production exists in the early stages of diabetic retinopathy. METHODS: Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n = 16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n = 16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-alpha and IL-1beta on IRBP expression and IRBP levels. RESULTS: Intravitreous IRBP concentration was significantly lower in PDR < NPDR < control in proteomic and western blot analysis. IRBP mRNA levels and IRBP protein content were significantly lower in the retinas from diabetic donors than in those from non-diabetic donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with non-diabetic retinas. A dose-dependent downregulation of IRBP mRNA expression and IRBP content was detected with glucose, TNF-alpha and IL-1beta in cultures of Y79 human retinoblastoma cells. CONCLUSIONS/INTERPRETATION: Underproduction of IRBP is an early event in the human diabetic retina and is associated with retinal neurodegeneration. The mechanisms leading to this deficit deserve further investigation.

Treatment of chronic diabetic foot ulcers with bemiparin: a randomized, triple-blind, placebo-controlled, clinical trial.

AIMS: To assess the efficacy and safety of bemiparin in the treatment of chronic diabetic foot ulcers. METHODS: A triple-blind, parallel, randomized, placebo-controlled trial. Patients aged > 18 years, [corrected] with diabetes for at least 3 years, and with a foot ulcer persisting for > 3 months were selected from 39 Spanish centres. Bemiparin 3500 IU/day for 10 days, followed by 2500 IU/day for up to 3 months plus standard care for ulcers, was compared with placebo plus standard care for ulcers for 3 months. The primary efficacy end-point was ulcer improvement, defined as an objective decrease in ulcer area of >or= 50%, measured by digital photography and ImageJ software, and/or any decrease in Wagner's ulcer grade at 3 months. RESULTS: Ulcer improvement rates were 70.3% (26 of 37 patients) in the bemiparin group and 45.5% (15 of 33 patients) in the placebo group [absolute difference 24.8; 95% confidence interval (CI) 2.3, 47.3; P = 0.035] (number needed to treat 4; 95% CI 2, 43). Complete healing rates at 3 months were similar in both groups (35.1% vs. 33.3%; P = 0.874), as were the number of adverse events. CONCLUSIONS: Bemiparin is more effective than placebo in the management of diabetic foot ulcers and has few side-effects.

Critical assessment of the current guidelines for the management and treatment of morbidly obese patients.

An interdisciplinary panel of specialists met in Mallorca in the first European Symposium on Morbid Obesity entitled; "Morbid Obesity, an Interdisciplinary Approach". During the two and half days of the meeting, the participants discussed several aspects related to pathogenesis, evaluation, and treatment of morbid obesity. The expert panel included basic research scientists, dietitians and nutritionists, exercise physiologists, endocrinologists, psychiatrists, cardiologists, pneumonologists, anesthesiologists, and bariatric surgeons with expertise in the different weight loss surgeries. The symposium was sponsored by the Balearic Islands Health Department; however, this statement is an independent report of the panel and is not a policy statement of any of the sponsors or endorsers of the Symposium. The prevalence of morbid obesity, the most severe state of the disease, has become epidemic. The current recommendations for the therapy of the morbidly obese comes as a result of a National Institutes of Health (NIH) Consensus Conference held in 1991 and subsequently reviewed in 2004 by the American Society for Bariatric Surgery. This document reviews the work-up evaluation of the morbidly obese patient, the current status of the indications for bariatric surgery and which type of procedure should be recommended; it also brings up for discussion some important real-life clinical practice issues, which should be taken into consideration when evaluating and treating morbidly obese patients. Finally, it also goes through current scientific evidence supporting the potential effectiveness of medical therapy as treatment of patients with morbid obesity.

[Triple-blind clinical trial with placebo control to evaluate the efficacy of a heparin of low molecular weight (bemiparin) for treating slow-responding ulcers in diabetic foot in primary care]. / Ensayo clínico, controlado con placebo, triple ciego, para evaluar la eficacia de una heparina de bajo peso molecular (bemiparina) en el tratamiento de las úlceras tórpidas del pie diabético, en atención primaria.

OBJECTIVES: To establish the degree of efficacy of bemiparin treatment over 3 months in the improvement of slow-responding ulcers in diabetic foot. Also, to evaluate the safety of bemiparin and quality of life and to compare the evolution of retinopathy and nephropathy against placebo. DESIGN: Stage III clinical trial to evaluate efficacy and safety in a new indication of a medicine already on the market, parallel in two branches, randomised, triple-blind, and controlled with placebo. SETTING: Health care centres in Mallorca, Spain. PARTICIPANTS: 42 patients per branch, over 18, with type-1 or 2 DM of over 3 years evolution, and one or more first or second-degree ulcers on the Wagner scale, distal to the knee, that did not heal in three months of health care. Randomised allocation in blocks of four.Interventions. The experimental drug was bemiparin (heparin of low molecular weight), injected subcutaneously at 3500 IU/day for the first 10 days and 2500 IU/day up to 90 days. As control, physiological serum was injected sub-cutaneously in a similar volume for masking. MAIN MEASUREMENTS: An "effect"was defined as a reduction of at least 50% in its surface area and/or a favourable evolution in status to a degree between the control at the start of treatment and at three months. Other measurements included proteinuria, retinography and quality of life (SF-36). Analysis of efficacy through principle of intention to treat.

Serum laminin as a marker of diabetic retinopathy development: a 4-year follow-up study.

PURPOSE: The usefulness of laminin as a serum marker of diabetic retinopathy is a topic that generates conflicting views. The aim of the present study was to investigate the effect of diabetic retinopathy on serum laminin-P1, the larger pepsin resistant fragment of laminin, and to elucidate whether serum laminin-P1 could be an indicator of the risk for development of diabetic retinopathy. METHODS: In a prospective study, 97 consecutive diabetic patients (35 type 1 and 62 type 2) without diabetic retinopathy and a urinary albumin excretion rate lower than 20 microg per minute were enrolled in a 4-year follow-up study. Patients who developed microalbuminuria during the study were excluded in order to avoid the influence of diabetic nephropathy on serum laminin-P1. At the end of follow-up, data from ophthalmologic studies and serum laminin-P1 were evaluated in the 66 normoalbuminuric diabetic patients who completed the study. RESULTS: No statistical differences were observed in baseline laminin-P1 serum concentrations between patients who developed diabetic retinopathy (n = 15) and patients who remained without it during follow-up (n = 51). However, serum laminin-P1 levels obtained at the end of the study were significantly higher in patients who developed diabetic retinopathy (1.75 +/- 0.33 U/ml versus 1.47 +/- 0. 27 U/ml; P =.002). Furthermore, statistical difference was observed when initial and final values of serum laminin-P1 were compared in patients who developed diabetic retinopathy (1.56 +/- 0.27 U/ml versus 1.75 +/- 0.33 U/ml; P =.001). Remarkably, an increase in serum laminin-P1 concentration was detected in all but two of the patients who developed diabetic retinopathy. The relative risk of development of diabetic retinopathy in patients who showed an increase in serum laminin-P1 during follow-up was 5.4 (95% confidence interval, 1.32 to 22.13). CONCLUSIONS: Serum laminin-P1 is a marker and a risk indicator of diabetic retinopathy but is not an early predictor of its development.

Effect of panretinal photocoagulation on serum levels of laminin in patients with diabetes: a prospective study.

BACKGROUND/AIM: Laminin, a major specific non-collagenous glycoprotein of basement membrane, has been proposed as an index of diabetic retinopathy and high serum concentrations have been reported in patients with proliferative diabetic retinopathy. On the other hand, panretinal photocoagulation (PRP) prevents the progression of severe diabetic retinopathy and reverses preretinal neovascularisation. The aim of the study was to investigate the effect of PRP on serum levels of laminin in patients with diabetes. METHODS: 20 patients with diabetes undergoing PRP and 15 patients with mild or moderate non-proliferative diabetic retinopathy in whom a PRP was not performed were included in the study. Serum laminin-P1 (Lam-P1), the largest pepsin resistant fragment of laminin, was determined by radioimmunoassay in each patient before starting PRP and 3 months after it was accomplished. Similarly, a baseline and a 4 month sample were analysed in the non-photocoagulated controls. RESULTS: Serum Lam-P1 concentrations obtained 3 months after PRP were significantly lower when compared with the initial values (1.62 (SD 0.36) U/ml v 1.91 (0.37) U/ml; p <0.001). A decrease of serum levels of Lam-P1 could be seen in all patients. By contrast, in those patients with mild or moderate non-proliferative diabetic retinopathy in whom a PRP was not performed, no significant changes were detected in serum Lam-P1 concentrations (1.72 (0.20) U/ml v 1. 74 (0.17); p=0.250). CONCLUSION: PRP decreases serum Lam-P1 levels in patients with severe diabetic retinopathy. Thus, the studies addressed to evaluate the usefulness of Lam-P1 as a marker of diabetic retinopathy should consider previous PRP as an influencing factor. Finally, our results suggest that retinal source of Lam-P1 strongly contributes to serum Lam-P1 in patients with severe diabetic retinopathy.

[Fibronectin and diabetes mellitus: the factors that influence its plasma concentrations and its usefulness as a marker of late complications]. / Fibronectina y diabetes mellitus: factores que influyen en las concentraciones plasmáticas y utilidad como marcador de complicaciones tardías.

BACKGROUND: The usefulness of plasma fibronectin (FNp) as a marker of late diabetic complications is controversial. The aim of the study was to assess the influence of several variables on FNp in diabetic patients and to determine its usefulness as a marker of late diabetic complications. PATIENTS AND METHODS: 79 diabetic patients randomly selected were included in the study. The clinical variables considered were: age, gender, body mass index (BMI), tobacco and alcohol consumption, type, duration and treatment of diabetes, hypertension, and diabetic late complications (macroangiopathy, retinopathy, nephropathy and neuropathy). The laboratory variables analyzed were: blood glucose, glycated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, tryglicerides, apolipoprotein AI, apolipoprotein B, microalbuminuria, creatinin and FNp. Statistical study included a multiple regression analysis taking FNp as the dependent variable. RESULTS: A direct correlation between FNp and BMI and also with tryglicerides was observed (r = 0.362; p = 0.002, and r = 0.234; p = 0.038, respectively). Higher levels of FNp were found in type 2 diabetic patients in comparison with type 1 (464 [SD, 127] versus 395 [SD, 96] mg/dl; p = 0.014). This difference was due to the higher BMI and tryglicerides concentrations observed in type 2 diabetic patients in comparison with type 1 (28.61 [SD, 4.67] versus 22.56 [SD, 2,.19] kg/m2; p < 0.001, and 4.24 [SD, 2.36] versus 2.52 [SD, 1.40] mmol/l, respectively). Multiple regression analysis showed that only BMI significantly influenced on FNp concentrations (r = 0.330; p = 0.004). No relation among FNp and late diabetic complications and other variables considered in the study was observed. CONCLUSIONS: FNp is not a useful marker of diabetic late complications and its concentrations are direct and independently influenced by BMI.

Leu-M1 immunoreactivity and phaeochromocytoma.

The aim was to evaluate Leu-M1 immunoreactivity as a prognostic factor in phaeochromocytoma. Anti-Leu-M1 monoclonal antibodies were used to determine the Leu-M1 immunoreactivity in 17 histologically confirmed phaeochromocytomas from 15 patients, using an avidin-biotin technique. Ten patients had a sporadic phaeochromocytoma, and five had multiple endocrine neoplasia type 2A (MEN 2A). Malignancy was diagnosed in three patients by the presence of metastases. Leu-M1 immunoreactivity was shown in 12 (70.5%) phaeochromocytomas. Three patterns of arrangement were observed: isolated (scattered positive cells) (n = 3); focal (aggregates of positive cells) (n = 5), and diffuse patterns (dispersed positive cells) (n = 4). Two cases of malignant phaeochromocytoma were positive (one focal and one isolated pattern). All cases of MEN 2A showed immunoreactivity, although no characteristic pattern was prevalent. A diffuse pattern was observed in all phaeochromocytomas longer than 7 cm. In conclusion, Leu-M1 expression is frequent in phaeochromocytoma. However, Leu-M1 immunoreactivity seems to be useless in predicting malignant behaviour and to be influenced mainly by tumour size.

[Differentiated thyroid carcinoma, 1972-1992. Follow-up, detection of recurrences and prognostic factors]. / Carcinoma diferenciado de tiroides, 1972-1992. Estudio evolutivo, detección de recurrencias y factores pronósticos.

BACKGROUND: There is no consensus about the treatment and the follow-up of differentiated thyroid carcinoma (DTC), because in some patients, currently known prognostic factors cannot predict the course of the disease. The aim of this work has been to review the results of the treatment of our patients with DTC and to assess the prognostic factors. PATIENTS AND METHODS: We include, retrospectively, 204 patients with DTC (54 males and 150 women) with a men (SD) age of 38 (23) years, attending to a terciary university hospital. The follow-up is 9.2 (6) years (range, 2-22 years). They all underwent near total thyroidectomy, ablative doses of radioactive iodine (131INa) and L-thyroxine to suppress thyroid stimulating hormone (TSH) levels. At least once a year, a clinical examination, a whole-body scan (WBS) with 131INa and serum thyroglobulin (Tg) measurements were performed in hypothyroid state. In the statistics, chi 2 test, univariate analysis, Student's t test, Kaplan-Meier method, Mantel-Cox test and multiple regression analysis were employed. RESULTS: The survival rate was 89.05%. Twenty patients died of DTC (9.8%) (papillary 8 [6%], follicular 12[17%]). Surgical complications (recurrent nerve palsy or permanent hypoparathyroidism) were seen in 5% of the patients. The sensitivity of WBS to detect distant metastases or local (neck) involvement was 71% (initial 100%, late 71%). Tg sensitivity was 85% (initial 95%, late 73%). Factors associated to a poor prognosis were age > 40 years (p < 0.0001), follicular carcinoma (p < 0.02) and initial stages III and IV (p < 0.0001). CONCLUSIONS: The mortality and complications rates in our patients with differentiated thyroid carcinoma validate our management schedule. Tg measurements are more sensitive than WBS to detect distant or local metastases; however, sensitivity of both techniques was lower in the detection of late metastases. Age below 40 years, papillary carcinoma and initial stages I and II are factors of better prognosis.

Serum concentrations of laminin-P1 in diabetes mellitus: usefulness as an index of diabetic microangiopathy.

OBJECTIVE: To assess the influence of several variables on serum laminin-P1 (Lam-P1) and to evaluate its usefulness as a serum marker of diabetic microangiopathy. MATERIAL AND METHODS: We determined Lam-P1 by serum radioimmunoassay in 121 controls and 176 diabetic patients, 58 type 1 (insulin dependent) and 118 type (non-insulin dependent), grouped according to retinal status and urinary albumin excretion. The variables evaluated were: age, gender, body mass index, blood pressure, consumption of tobacco and alcohol, type of diabetes, duration of disease, fasting blood glucose, HbA1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and apolipoproteins (A1, B). Imprecision for laminin determination was: 3.6% intrassay; 5.8% interassay. STATISTICS: Student's t-test, ANOVA, ANCOVA, and multiple regression analysis. RESULTS: In diabetic patients Lam-P1 was higher than in controls (X = 1.63 +/- S.D. 0.36 vs. X = 1.40 +/- S.D. 0.18 U ml-1; P < 0.001) and only correlated with age (P = 0.002). Lam-P1 was higher in diabetics with proliferative retinopathy than in patients with non-proliferative retinopathy and without retinopathy (X = 2.17 +/- S.D. 0.49 U ml-1 vs. X = 1.71 +/- S.D. 0.22 U ml-1 vs. X = 1.47 +/- S.D. 0.26 U ml-1; P < 0.001). Patients with macroalbuminuria presented higher serum Lam-P1 than patients with micro or normoalbuminuria (X = 2.39 +/- S.D. 0.53 U ml-1 vs. X = 1.78 +/- S.D. 0.23 U ml-1 vs. X = 1.51 +/- S.D. 0.29 U ml-1; P < 0.001). These differences remained significative when patients were age-adjusted. CONCLUSIONS: Lam-P1 could be useful as an index of diabetic microangiopathy but patient's age should be considered.