MUSCLE INFARCTION AND SEVERE DETERIORATION OF RENAL FUNCTION IN A PATIENT WITH TYPE 1 DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE.

CONTEXT: Spontaneous muscle infarction is a rare complication of diabetes mellitus, mainly affecting women and patients with long-lasting type 1 diabetes. OBJECTIVE: This report is aimed to describe the case of a patient with type 1 diabetes and diabetic nephropathy in whom a severe deterioration of renal function was triggered by a muscle infarction. SUBJECT AND METHODS: Subject of the study was a 33-years-old woman with an 18 years history of type 1 diabetes mellitus, proliferative diabetic retinopathy, nephropathy at stage 3 chronic kidney disease, somatic sensory-motor polyneuropathy and autonomic neuropathy. RESULTS: The patient presented with severe pain and dysfunction of the left thigh without prior trauma plus progressive deterioration of the renal function. Nuclear magnetic resonance of the thigh showed inflammatory changes in the external vastus with hyperintensity on T2 sequence and edema of the subcutaneous cellular tissue. After other possible etiologies were ruled out, a clinical diagnosis of spontaneous muscle infarction was established. The patient needed hospital admission for two months, during which the renal function worsened until she required hemodialysis. No other possible triggers of kidney injury were identified. CONCLUSIONS: Up to our knowledge, this is the first described case where muscle infarction is suspected to have caused exacerbation of an existing chronic kidney failure. Monitoring the renal function should be considered in patients with diabetic nephropathy presenting with this rare complication of diabetes.

Insulin resistance explains the relationship between novel cardiovascular risk factors and hypertension. The Telde Study.

BACKGROUND: Most studies describing an association between hypertension and an inflammatory/pro-thrombotic state do not assess insulin resistance. AIM: To examine the association between hypertension and new cardiovascular risk factors when considering both classical risk factors and insulin resistance. METHODS: In a population-based sample of 1030 subjects, clinical information and blood samples were obtained. Subjects were classified according to the presence or absence of hypertension, and insulin resistance was estimated using the homeostasis model of assessment (HOMA). To identify variables independently associated with hypertension, a four-model multiple logistic regression was performed: model 1 included novel risk factors (Plasminogen Activator Inhibitor- 1 [PAI-1], fibrinogen, von Willebrand Factor [vWF], lipoprotein(a), homocysteine and C-reactive Protein [CRP]); model 2, novel risk factors plus HOMA; model 3 included both classical (smoking, triglycerides, HDL cholesterol, total cholesterol, waist circumference and diabetes) and novel risk factors and model 4, model 3 plus HOMA. All were adjusted for age, BMI and gender and compared using Akaike's Information Criterion (AIC). RESULTS: In model 1, only PAI-1, age and BMI showed association with hypertension.When HOMA and classical risk factors were also included, PAI-1 was replaced by triglyceride, smoking and diabetes. The lowest AIC value (best adjustment) was displayed by model 4, comprising all of the variables. Only age, BMI, HOMA and smoking remained significantly associated with hypertension. CONCLUSIONS: The novel cardiovascular risk factors assessed do not add information as markers of hypertension when classical risk factors or insulin resistance are included in the evaluation.

Association of Taq 1B CETP polymorphism with insulin and HOMA levels in the population of the Canary Islands.

BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) is an enzyme with a key role in lipoprotein metabolism. A common genetic polymorphism, the Taq 1B, influences CETP activity and HDL-cholesterol levels, with individual homozygotes for the B1 allele exhibiting higher enzyme activity and lower HDL-cholesterol levels than carriers of at least one B2 allele. Our aim was to analyze the influence of Taq 1B CETP polymorphism on cardiovascular risk factors in a representative sample of adult subjects from Canary population. METHODS AND RESULT: A total of 518 adult subjects from the Canary Islands, enrolled in a nutritional survey (the ENCA study), were included. The Taq 1B polymorphism was analyzed by PCR-RFLP. Compared with individuals with at least one B2 allele, and after adjusting for age, sex, BMI, waist perimeter, smoking and alcohol intake, carriers of the B1B1 genotype showed lower HDL-cholesterol levels (geometric mean (95% CI): 46.6 (44.5-48.8) vs. 50.6 (49.1-52.9)mg/dl; P=0.003); and higher insulin (geometric mean (95% CI): 11.1 (10.5-11.9) vs. 10.0 (9.5-10.5µU/ml; P=0.008) and HOMA levels (geometric mean (95% CI): 2.3 (2.1-2.5) vs. 2.1 (1.9-2.1); P=0.009). In addition, the B1B1 genotype was more frequent in individuals who had low levels of HDL-cholesterol according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (Odds Ratio (OR): 1.563; 95% CI: 1.04-2.34; P=0.030), and in those included in the upper quartile of insulinemia (OR: 1.90; 95% CI: 1.20-3.03; P=0.007) and HOMA (OR: 1.61; 95% CI: 1.02-2.57; P=0.043). CONCLUSION: The observed influence of Taq 1B polymorphism on insulin levels and HOMA highlights the possible role of CETP in the regulation of glucose homeostasis.

Thyrotropin levels and their relationship with cardiovascular risk factors in the island of Gran Canaria, Spain. Implications of lowering the upper reference limit of thyrotropin stimulating hormone.

OBJECTIVE: To characterize the cardiovascular risk profile of subjects with high and normal-high concentrations of serum TSH in a sample of adult Spanish subjects from the island of Gran Canaria. DESIGN: Cross-sectional population-based study. SUBJECTS: After excluding 28 individuals on current treatment with levothyroxine and 9 others with TSH levels below the range of normality (0.3-4.9 mU/l), 704 randomly selected subjects (412 women; age range: 30-82 yr) belonging to the Telde Study were assessed. MEASUREMENTS: Participants underwent physical examination and fasting blood analyses to determinate TSH, serum lipids, homocysteine, fibrinogen, von Willebrand factor, plasminogen activator inhibitor- 1, C-reactive protein, and insulin. RESULTS: Twenty-nine participants had serum TSH concentrations above the normal range of normality. Among all the studied variables, only female sex and diastolic blood pressure were significantly associated with TSH levels > or =5 mU/l in a multivariate logistic regression analysis. If the upper normal limit of TSH was reduced up to 2.4 mU/l, an additional group of 106 subjects would be considered to have elevated TSH levels. A serum TSH > or =2.5 mU/l was positive and independently associated with female sex, body mass index, total cholesterol, and homocysteine, and negatively associated with smoking. CONCLUSIONS: Although the impact of serum TSH levels on cardiovascular risk cannot be established from these findings, TSH values within the upper part of the usually accepted normal range were demonstrated to be associated with well-recognized risk factors for cardiovascular disease.

Use of confirmatory factor analysis for the identification of new components of the metabolic syndrome: the role of plasminogen activator inhibitor-1 and Haemoglobin A1c.

BACKGROUND AND AIM: This study was aimed to identify additional components of metabolic syndrome from a set of cardiovascular risk markers. METHODS AND RESULTS: The homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, homocysteine, Haemoglobin A1c (HbA1c), and lipoprotein(a) were assessed in a population-based sample of 902 nondiabetic adult subjects. Those biomarkers that were associated with metabolic syndrome were evaluated by multiple regression analysis, along with other traditional cardiovascular risk factors. Confirmatory factor analysis (CFA) was used to test the hypothesis that both the established components of metabolic syndrome and the novel variables identified by the regression analysis were associated with a single underlying factor. HOMA-IR, PAI-1 and HbA1c were the only biomarkers independently related to metabolic syndrome. CFA validated a one-factor model that included these variables. Moreover, the indices of goodness of fit were better for this expanded model than those obtained for a previously validated one-factor model that was restricted to the conventional elements of the syndrome. CONCLUSIONS: These findings show that PAI-1 and HbA1c are singularly linked to metabolic syndrome. Their elevation is presumably another manifestation of the same pathophysiological mechanism that underlies the recognized traits of the syndrome.

Differences in traditional and emerging cardiovascular risk factors of subjects discordantly classified by metabolic syndrome definitions of the International Diabetes Federation and the National Cholesterol Education Program.

BACKGROUND AND AIM: Several working definitions of metabolic syndrome have been proposed for clinical use. However, individuals can be discordantly classified as having or not having metabolic syndrome depending on the choice of one or another definition. This study compared the cardiovascular risk profile of subjects concordantly and discordantly diagnosed by the criteria of the National Cholesterol Education Program (NCEP) and the criteria of the International Diabetes Federation (IDF). METHODS AND RESULTS: Nine hundred and twenty-nine non-diabetic adult subjects belonging to a cross-sectional population-based study in Gran Canaria island (Spain) were assessed. Participants completed a questionnaire and underwent physical examination, fasting blood analyses, and a standardized oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5 (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol, triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1 (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in contrast to subjects meeting both criteria, those that fulfilled only the IDF criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose, glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly different from those observed in subjects without metabolic syndrome. CONCLUSION: The IDF definition identifies a surplus of individuals whose cardiovascular risk profile, particularly regarding to some non-traditional cardiovascular risk factors, is less adverse than that observed in subjects also diagnosed by the NCEP definition.

Diabetes mellitus and impaired glucose regulation in the Canary Islands (Spain): prevalence and associated factors in the adult population of Telde, Gran Canaria.

AIMS: To estimate the prevalence and the determinants of diabetes mellitus and impaired glucose regulation (IGR) in an adult Canarian population. METHODS: Cross-sectional study. One thousand and thirty subjects aged 30-82 years were randomly selected. Participants completed a survey questionnaire and underwent blood pressure measurements, anthropometry, blood samples, and a 75-g standardized oral glucose tolerance test. RESULTS: The age-standardized prevalence of diabetes was 15.8% (95% confidence interval: 11.8-19.8) in men and 10.6% (7.1-14.1) in women. Total prevalence was 13.2% (11.1-15.2). Among individuals with diabetes, 55.4% of men and 38.2% of women were not previously diagnosed. The age-standardized prevalences of impaired glucose tolerance and impaired fasting glycaemia were 11.4% (9.5-13.4) and 2.8% (1.8-3.8), respectively. In multivariate analyses, age, waist circumference, serum triglycerides, and familial history of diabetes were independently associated with diabetes in both sexes, while a value of C-reactive protein (CRP) >/= 1 mg/l showed an association with diabetes, but only in men. Age and triglycerides were related to impaired glucose regulation (IGR) in both sexes, waist circumference was related to IGR exclusively in men, and familial diabetes exclusively in women. Statistically significant interactions between gender and both CRP and triglycerides were found with respect to diabetes, and between gender and both waist circumference and triglycerides for IGR. CONCLUSIONS: Compared with the rest of Spain, the prevalence of diabetes is moderately increased in this area of the Canary Islands. Along with other well-established risk factors, CRP was independently associated with diabetes, but only in the male population.

Prevalence of the metabolic syndrome in the island of Gran Canaria: comparison of three major diagnostic proposals.

AIMS: The present study was conducted to estimate the prevalence of the metabolic syndrome in a Canarian population, and to compare its frequency as defined by the most commonly used working definitions. METHODS: Cross-sectional population-based study. One thousand and thirty adult subjects were randomly selected from the local census of Telde, a city located on the island of Gran Canaria. Participants completed a survey questionnaire and underwent physical examination, fasting blood analyses, and a 75-g standardized oral glucose tolerance test. The prevalence of the metabolic syndrome was estimated according to the definitions proposed by the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR) and the National Cholesterol Education Program (NCEP), the latter with the original (6.1 mmol/l) and the revised criterion (5.6 mmol/l) for abnormal fasting glucose. RESULTS: The adjusted prevalence of the metabolic syndrome was 28.0, 15.9, 23.0 and 28.2%, using the WHO, EGIR, NCEP and revised NCEP criteria, respectively. The measure of agreement (kappa statistic) was 0.57 between the WHO and the original NCEP definitions, and 0.61 between the WHO and the revised NCEP definitions. After excluding diabetic subjects, the agreement between the EGIR and WHO proposals was fairly good (kappa=0.70), whereas concordance of the EGIR with the original and the revised NCEP definitions was moderate (kappa=0.47 and 0.46, respectively). CONCLUSIONS: Whichever the considered diagnostic criteria, the prevalence of the metabolic syndrome in this area of the Canary Islands is greater than that observed in most other European populations.

Clinical manifestations and hormonal profile of two women with Cushing's disease and mild deficiency of 21-hydroxylase.

The development of Cushing's disease among patients with deficiency of 21-hydroxylase has not been observed to date. The clinical manifestations and the hormonal profile of this exceptional association are herein described through the study of two cases. The first one was a 39-yr-old woman who had undergone non-curative transsphenoidal surgery for a pituitary-dependent Cushing's syndrome 12 yr before. She showed hypertension, central obesity, severe hirsutism, alopecia and hyperpigmentation. Urinary excretion of cortisol was normal, but ACTH levels were very high and hormonal dynamic studies (cortisol circadian rhythm, insulin-induced hypoglycemia and dexamethasone suppression tests) revealed the qualitative disturbances that characterize Cushing's disease. Serum concentrations of androstenedione, free testosterone and 17-hydroxyprogesterone were clearly increased. Reexamination of the tissue samples from previous surgery confirmed the presence of an ACTH-producing pituitary adenoma. CYP21 gene analysis found the splicing 655G mutation at intron 2 and the V281L mutation at exon 7. The second case was a 21-yr-old woman who was diagnosed with pituitary ACTH-dependent Cushing's syndrome according to unequivocal clinical and laboratory findings. However, hirsutism was particularly severe and both serum androgens and 17-hydroxyprogesterone were elevated. The patient was heterozygote for a large conversion of CYP21 gene. In these cases, the clinical and biochemical expression of Cushing's syndrome was determined by the different severity of 21-hydroxylase deficiency and the subsequent residual ability of adrenal cortex to synthesize cortisol.

Effects of tamoxifen on lipid profile and coagulation parameters in male patients with pubertal gynecomastia.

BACKGROUND/AIM: The estrogenic actions of tamoxifen on lipid profiles and hemostasis have been extensively demonstrated in women. Due to limited experience with this drug in males, it is uncertain whether these effects are also present in men. The aim of our study was to assess the response of blood lipids, lipoproteins, and coagulation parameters in a group of men taking tamoxifen. METHODS: We studied 15 healthy boys with pubertal gynecomastia who were given 10 mg tamoxifen per day. Total testosterone, sex-hormone-binding globulin, estradiol, serum lipids, apolipoprotein B, apolipoprotein A-I, lipoprotein(a), fibrinogen, antithrombin III, von Willebrand factor, and markers of activated coagulation and fibrinolysis were determined at baseline and 1 and 3 months after beginning of the tamoxifen treatment. RESULTS: Total cholesterol and lipoprotein(a) showed moderate but significant decreases from baseline. Low-density lipoprotein and high-density lipoprotein cholesterol concentrations as well as triglyceride and apolipoprotein B levels became lower, but these changes were not statistically significant. Among clotting parameters, antithrombin III was reduced, and von Willebrand factor increased significantly. Markers of activated coagulation and fibrinolysis remained unchanged throughout the period of therapy. CONCLUSIONS: The effects of tamoxifen on blood lipids and hemostasis we found in this group of healthy young men were qualitatively similar, but lesser than those previously described in women.

[Central diabetes insipidus as clinical presentation of a bronchogenic adenocarcinoma]. / Diabetes insípida central como presentación clínica de un adenocarcinoma bronquial.

Metastatic tumors of the pituitary gland are uncommon. The majority of them are silent lesions incidentally discovered at autopsy. In contrast, the occurrence of symptomatic metastases is exceptional. Here we report the clinical and radiological findings of a 45 year-old woman with a metastatic lung adenocarcinoma who presented with diabetes insipidus and hypernatremic dehydration. There was no previous history of malignancy, and the pituitary metastases were responsible for the first manifestation of the disease. Clinical presentation, diagnosis and therapeutic management of patients with pituitary metastases are reviewed.