Early blood pressure alterations are associated with pro-inflammatory markers in type 1 diabetes mellitus.

The aim of this study was to evaluate the relationship between early blood pressure (BP) changes (detected using ambulatory BP monitoring; ABPM) with different markers of inflammation and endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The study design was observational cross-sectional in 85 T1DM patients, clinically normotensive and with normo-albuminuria. We analyzed the relationships between ABPM-measured BP alterations over 24 h with the inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α and vascular endothelial growth factor (VEGF)) and the markers of endothelial damage (vascular adhesion molecule, intercellular adhesion molecule and plasminogen activator inhibitor-1 (PAI)). Despite being recorded as normotensive, 27 (31.8%) subjects presented with an average of pathological BP. VEGF levels were significantly elevated in the patients with an altered mean diurnal values compared with normotensives (112.33 (72.87-213.53) pg ml-1 vs 71.03 (37.71-107.92) pg ml-1; P=0.007). Further, VEGF levels correlated significantly with the parameters of diurnal BP and of 24 h values. IL-6 concentration was a risk factor in the patients with hypertension (OR=1.406; P=0.027). There were no modifications in the levels of markers of endothelial damage. Summarizing, there is an increase in pro-inflammatory cytokines, but not the endothelial adhesion molecules, in early stages of arterial hypertension in patients with T1DM.

[Effect of gastric bypass on the cardiovascular risk and quality of life in morbid obese patients]. / Efecto del bypass gástrico sobre el riesgo cardiovascular y la calidad de vida en pacientes con obesidad mórbida.

OBJECTIVES: To determine the prevalence of major comorbidities of morbidity obese patients and to evaluate the gastric bypass effect on the weight status, cardiovascular risk and quality of life in these patients. METHODS: The evolution of weight, comorbidity, 10- year follow-up of cardiovascular risk (estimated by the Framingham risk score) and quality of life using the test BAROS (Bariatric Analysis and Reporting Outcome System) was analyzed in 162 patients with morbid obesity before and 2 years after gastric bypass. RESULTS: Body mass index (BMI) was reduced from 51.12 ± 7.22 to 29.94 ± 4.86 kg/m2 (72.85% loss of excess weight). Hypertension (HT), dyslipidemia and type 2 diabetes mellitus (T2DM) were resolved in 71.93%, 91.38% and 82.93% respectively (p < 0.001). Cardiovascular risk greater than 10% was reduced from 25.91% to 4.32% (p < 0.001). According to BAROS scale, surgery was positive in 95% of cases. CONCLUSIONS: Gastric bypass is very effective in weight loss; benefits in comorbidities, cardiovascular risk and quality of life.

Objetivos: Determinar la prevalencia de las principales comorbilidades asociadas a la obesidad mórbida y evaluar el efecto del bypass gástrico sobre el estado ponderal, riesgo cardiovascular y calidad de vida en estos pacientes. Métodos: Estudio descriptivo con medidas del cambio intrasujeto (antes-después) en una muestra de 162 pacientes de los resultados del bypass gástrico sobre la evolución ponderal, comorbilidades asociadas, riesgo cardiovascular a 10 años (estimado mediante las tablas de Framingham) y calidad de vida mediante el test BAROS (Bariatric Analysis and Reporting Outcome System). Resultados: El índice de masa corporal (IMC) se reduce de 51,12 ± 7,22 kg/m2 a 29,94 ± 4,86 kg/m2 (72,85% de sobrepeso perdido) y se resuelven la hipertensión arterial (HTA), la dislipemia y la diabetes mellitus tipo 2 (DMT2) en el 71,93%, 91,38% y 82,93% respectivamente (p < 0,001). El riesgo cardiovascular mayor del 10% se reduce del 25,91% al 4,32% (p < 0,001). Según la escala BAROS, el resultado de la cirugía fue favorable en el 95% de los casos. Conclusiones: La cirugía bariátrica mediante bypass gástrico demuestra ser muy efectiva para la reducción ponderal y comorbilidades asociadas, mejorando notablemente la calidad de vida.

Postpartum development of endothelial dysfunction and oxidative stress markers in women with previous gestational diabetes mellitus.

BACKGROUND: Relationships between adhesion molecules (AM), oxidative stress, gestational diabetes mellitus (GDM) and future development of type 2 diabetes mellitus are unclear. AIM: We investigated AM and oxidant/antioxidant markers in women with previous history of GDM. SUBJECTS AND METHODS: Postpartum women with GDM (cases; n = 41) and healthy women (controls; n = 21) had clinical and laboratory variables measured, including indicators of vascular damage (ICAM-1, VCAM-1 and E-selectin), oxidative stress (LPO, GSH and GST) and antioxidant markers (catalase, SOD, GPX and TAC). RESULTS: Previous GDM versus control women presented higher body mass index: 27.4 ± 5.6 versus 23.9 ± 3.6 (p = 0.013); waist circumference: 85.2 ± 12.9 versus 77.5 ± 9.0 (p = 0.017); MetS (WHO definition): 14.6 versus 0 % (p = 0.012); MetS (NCEP-ATPIII definition): 22 versus 0 % (p = 0.002); low HDL: 36.6 versus 9.5 % (p = 0.024); fasting glucose (mmol/L): 5.4 ± 0.6 versus 4.9 ± 0.2 (p < 0.001); glucose 120 min (mg/dL): 105.0 ± 30.2 versus 85.1 ± 14.2 (p = 0.007); fasting insulin (µU/mL): 13.4 ± 8.1 versus 8.4 ± 4.3 (p = 0.004); HOMA index: 3.3 ± 2.3 versus 1.8 ± 1.0 (p = 0.002); HbA1c (%/mmol/mol): 5.4 ± 0.2 versus 5.2 ± 0.2/36 ± 1.4 versus 33 ± 1.4 (p = 0.021); uric acid (mg/dL): 4.1 ± 1 versus 3.5 ± 0.6 (p = 0.009); catalase (nmol/min/mL): 38.7 ± 15.6 versus 28.9 ± 11.1 (p = 0.013). There were no significant differences in hypertension prevalence, lipid fractions, albumin/creatinine ratio and AM. CONCLUSIONS: Women with previous GDM have high catalase levels which correlate positively with glucose intolerance, indicating the potential effect of oxidative stress on postpartum dysglycemic status.

Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus.

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m(2) (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.

Alterations in arterial pressure in patients with Type 1 diabetes are associated with long-term poor metabolic control and a more atherogenic lipid profile.

AIM: To determine the prevalence of alterations in blood pressure (BP) in patients with Type 1 diabetes who are normoalbuminuric and normotensive; and to evaluate the association with genetic, clinical and metabolic factors. MATERIAL/ METHODS: Normoalbuminuric, normotensive Type 1 diabetic patients (no.=85) had their ambulatory blood pressure monitoring (ABPM) performed over 24 h, together with measurement of HbA1c and lipid profile, polymorphisms of the ACE gene, non-midriatic retinography, and the "historical HbA1c" calculated (mean of all the determinations available on the patient). RESULTS: Of the 85 patients, a mean of 18.8% had pathologic values of BP over the 24 h, 31.8% during active periods and 22.4% during rest periods; in 42% there was a non-dipper pattern in BP. The patients with alterations of BP had higher body mass index (BMI), higher levels of glycemia and of triglycerides, and decreased levels of HDL cholesterol. The "historical HbA1c" was significantly higher in the patients with the non-dipper pattern (8.6 ± 1.4% vs 7.9 ± 1.4%; p=0.046). Pulse pressure was directly associated with male gender (p=0.006) and with BMI (p=0.001). No differences were detected in the distribution of the polymorphisms of the ACE gene as a function of the BP alterations. CONCLUSIONS: An elevated number normoalbuminuric, normotensive, Type 1 diabetic patients have alterations in BP detected with ABPM over 24 h, and these are associated with a greater BMI, poor long-term metabolic control and a more atherogenic lipid profile.

Benefits of continuous subcutaneous insulin infusion in type 1 diabetes previously treated with multiple daily injections with once-daily glargine and pre-meal analogues.

BACKGROUND/AIMS: There is insufficient information about the use of continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) using long-acting insulin analogs in relation to possible metabolic consequences and, as well, on the grade of patient satisfaction. The aim of the study was to evaluate the usefulness of CSII treatment in patients with type 1 diabetes in achieving glycemic objectives using continuous glucose monitoring system (CGMS) and in improving patient's satisfaction with treatment. METHODS: We have studied 45 type 1 diabetic patients treated with MDI with once-daily glargine and pre-meal rapid-acting insulin analogues, and 20 patients who commenced CSII because they had not achieved a good glycemic control. RESULTS: With CSII, there were significant reductions in insulin requirements (0.75+/-0.21 vs. 0.64+/-0.21 UI/kg/day; p=0.001), HbA (1c) (7.99+/-0.76 vs. 7.19+/-0.51%; p=0.001) and hypoglycemic episodes (4.60+/-1.82 vs. 3.05+/-1.88 events/patient/week; p=0.031) and improved patient satisfaction with treatment. CSII reduced hyperglycemic episodes in 04:00-08 h period (131.65+/-113.49 vs. 69.70+/-101.52 min; p=0.049), 24 h period area-under-the-curve (AUC) (4521.60+/-3689.23 vs. 3000.36+/-493.96 mmol/L x min; p=0.025) and AUC before dinner (217.36+/-181.46 vs. 136.22+/-202.88 mmol/L x min; p=0.048). CONCLUSIONS: In selected patients with poor metabolic control with once-daily glargine and pre-meal rapid-acting insulin analogues, CSII is a good alternative since it reduces hypoglycemic episodes and insulin requirement and improves glycemic control and patient's satisfaction.

Anti-proliferative effect of pro-inflammatory cytokines in cultured beta cells is associated with extracellular signal-regulated kinase 1/2 pathway inhibition: protective role of glucagon-like peptide -1.

Pancreatic beta-cell homeostasis is a balance between programmed cell death (apoptosis) and regeneration. Although autoimmune diabetes mellitus type 1 (DM1) is the most-studied cause of beta-cell mass loss by pro-inflammatory cytokine-induced apoptosis, influences of a pro-inflammatory environment on beta-cell regenerative response have been poorly studied. In this study, we assess the anti-proliferative effect of pro-inflammatory cytokines and glucose concentration on rat pancreatic beta cells and the potential protective role of glucagon-like peptide (GLP-1). Apoptotic and proliferating islet cells were stained using the DeadEnd Fluorimetric TUNEL System and 5-bromo-2'-deoxyuridine label respectively, in the presence-absence of varying concentrations of glucose, pro-inflammatory cytokines, and GLP-1. The potential signaling pathways involved were evaluated by western blot. Considerable anti-proliferative effects of pro-inflammatory cytokines interleukin (IL)-1beta, interferon (IFN)-gamma, and tumour necrosis factor-alpha (TNF-alpha) were observed. The effects were synergistic and independent of glucose concentration, and appeared to be mediated by the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) activation, the signaling pathway involved in beta-cell replication. GLP-1 completely reversed the cytokine-induced inhibition of ERK phosphorylation and increased beta-cell proliferation threefold in cytokine-treated cultures. While pro-inflammatory cytokines reduced islet cell ERK1/2 activation and beta-cell proliferation in pancreatic islet culture, GLP-1 was capable of reversing this effect. These data suggest a possible pharmacological application of GLP-1 in the treatment of early stage DM1, to prevent the loss of pancreatic beta cells as well as to delay the development of overt diabetes.

[Economic costs associated to type 1 diabetes]. / Costes económicos asociados a la diabetes tipo 1.

OBJECTIVE: The objective of our study was to determinate the health resource utilization and economic cost associated to diabetes in a patient group with type 1 diabetes. PATIENTS AND METHODS: We designed a cross-sectional study that involved 71 type 1 diabetes patients (59.4% women) with 29.2 +/- 12.2 years old mean age and 10.5 +/- 7.9 years of diabetes evolution attended in Endocrinology Service of Puerta del Mar Hospital in Cádiz. Direct and indirect cost associated to diabetes during a year period were determinated by information obtained from patient medical history and hospital, emergency, primary care and medical inspection of social insurance databases. RESULTS: Type 1 diabetes patients presented a total cost associated to diabetes of 3.311 euros/patient/year (95% IC: 2.202-4.420 euros/patient/year). Direct cost (2.104 euros/patient/year; 95% IC: 1.825-2.383 euros/patient/year) was higher than indirect cost (1.250 euros/patient/year; 95% IC: 291-2.225 euros/patient/year). Multiple regression analysis showed an independent association between total cost associated to diabetes (dependent variable) and variables number of hospitalizations related to diabetes (p = 0.006), pensioner situation (p = 0.02) and micro and macrovascular complications (p = 0.001). CONCLUSIONS: We conclude that economic cost associated to type 1 diabetes is important and presents a notable and independent increase with hospitalizations related to diabetes, pensioner situation and micro and macrovascular complications.

High glucose potentiates cytokine- and streptozotocin-induced apoptosis of rat islet cells: effect on apoptosis-related genes.

Pancreatic beta-cell apoptosis is known to participate in the beta-cell destruction process that occurs in diabetes. A better understanding of how it takes place is essential for future development of therapeutic strategies aimed at preventing beta-cell loss and diabetes. In this study we determine the possible role that high glucose concentration might play as an enhancer of cytokine- and streptozotocin (STZ)-mediated rat islet cell apoptosis in vitro and its relationship with potential changes in the expression of pro- and anti-apoptotic proteins. Rat islets treated with a cytokine combination (interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma) displayed a significant increase in islet cell apoptosis when the islets were incubated in 24.4 mM glucose compared with untreated islets at the same glucose concentration (13.07 +/- 1.78% vs 6.09 +/- 0.78%; P < 0.01) or islets incubated in 5.5 mM glucose concentration and cytokines (13.07 +/- 1.78% vs 8.04 +/- 1.56%; P < 0.05). IL-1beta alone did not induce a significant increase in the apoptotic rates in islet cells cultured at normal or high glucose concentrations. STZ significantly increased islet cell apoptosis when islets were cultured in 24.4 mM glucose concentration compared with untreated islets at the same glucose concentration (6.02 +/- 0.62% vs 4.44 +/- 0.63%; P < 0.05). High glucose induced an increase in Fas expression in the islet cells, and this increase was maintained after cytokine or STZ treatment. However, the expression of anti-apoptotic mediators such as bcl-2 and bcl-xL did not show any significant change. These results suggest that cytokine- and STZ-mediated apoptotic effects on islet cells might be mediated by a glucose-induced hyperfunctional status and associated with an increase in Fas (Apo-1, CD-95) expression and no changes in the expression of the anti-apoptotic proteins bcl-xL and bcl-2.

[Pituitary apoplexy: retrospective study of 9 patients with hypophyseal adenoma]. / Apoplejía pituitaria: análisis retrospectivo en 9 pacientes con adenomas hipofisarios.

Pituitary apoplexy is an acute hemorrhage or ischemia infarction of the pituitary gland, almost invariably occurring in the presence of an pituitary adenoma. Although intratumoral bleeding occur in about 9.5 to 25% of pituitary adenomas, various series suggest that clinical apoplexy may be diagnosed in about 2% to 10% of the adenomas. In a retrospective study from 1988 to 1998 of 110 patients with hypophyseal adenomas, there were 9 cases with pituitary apoplexy, yielding an incidence of 8.2%. Their mean age was 52.4 +/- 12.8 años years, with a male to female ratio of 7:2. Symptoms observed were headache (89%), sudden visual deterioration (78%), vomiting (78%) and oculomotor nerves paresis (33%). The diagnosis of pituitary apoplexy was established by computerized tomographic scans, and hypophyseal macroadenoma with intratumoral bleeding was observed in every patient. Five patients underwent transphenoidal surgery. Improvement of visual deficit was observed in 3/4 (75%) and ocular paresis in 3/3 (100%) of affected patients. Four patients were treated conservatively with steroids. Two patients who had visual deficit recovered it completely without surgery. Two hypophyseal adenomas were resolved spontaneously after bleeding, one stayed unchanged and another presented recurrence of bleeding at six years of follow-up. Steroid and thyroid hormone replacement therapy was required in 62.5% of patients.

Glutamic acid decarboxylase antibodies in non-insulin-dependent diabetes patients with secondary sulfonylurea failure in Thailand.

The objective of this study was to determine the frequency of glutamic acid decarboxylase antibody (GAD-Ab) in Thai non-insulin-dependent diabetes (NIDDM) patients who had secondary sulfonylurea failure. Sera were collected from 40 NIDDM patients, who had history of secondary failure to treatment with sulfonylurea, for analysis of fasting c-peptide and GAD-Ab. Both c-peptide and GAD-Ab were measured using radioimmunoassay method. Of 40 patients, ten (25.0%) were positive for GAD-Ab with a mean level of 59.9 U/ml (median 58.5, range 3.4-127). Patients with (GAD-Ab (+) had a significantly lower fasting c-peptide levels than those with GAD-Ab(-) albeit shorter duration of diabetes (0.21 +/- 0.19 (S.D.) versus 0.52 +/- 0.33 nmol/l; P = 0.003). Duration of treatment with sulfonylurea in patients with GAD-Ab (+) was also shorter (4.6 +/- 3.5 versus 10.4 +/- 5.5 years; P = 0.001). Age at onset of diabetes did not differ between these two groups. Among 40% of patients who had insulin deficiency (fasting c-peptide level < 0.33 nmol/1), GAD-Ab was present in half and these GAD-Ab(+) patients had significantly shorter duration of sulfonylurea treatment (3.3 +/- 2.3 versus 10.0 +/- 7.9 years; P = 0.018). In conclusion, the frequency of GAD-Ab in Thai NIDDM patients with secondary sulfonylurea failure in this study was 25%. Almost all GAD-Ab(+) patients had insulin deficiency and most had been initially treated with sulfonylurea for a few years before depending on insulin. This group of patients represents a slowly progressive type I or latent autoimmune diabetes in adult diabetic population.

Thyroid nodules. Role of fine needle aspiration and intraoperative frozen section examination.

OBJECTIVE: To determine the accuracy of fine needle aspiration (FNA) and intraoperative frozen section examination (IFSE) on thyroid nodules. STUDY DESIGN: The study group consisted of 470 patients who underwent thyroidectomy. FNA was performed on 289 patients and IFSE on 326. The FNA and IFSE results were compared with the final histologic diagnosis obtained after examination of permanent sections. RESULTS: The overall FNA sensitivity was 65%, specificity 88% and positive predictive value 61%. The IFSE sensitivity was 50%, and the specificity and positive predictive value were 100%. When both procedures were used together, FNA identified 16 of 45 (36%) carcinomas as malignant and an additional 13 (29%) as follicular proliferative lesions; IFSE correctly identified only 23 of 45 (51%) carcinomas. CONCLUSION: FNA provides enough information for determining the extent of thyroid surgery when a diagnosis of cancer is made. However, IFSE should be considered a supplementary procedure when FNA is not positive for cancer.

Reclassification after delivery of diabetes in pregnancy.

Gestational diabetes mellitus (GDM) constitutes a risk factor for the development of non insulin-dependent diabetes mellitus (NIDDM). The search for parameters to provide discrimination between a high risk and a low risk for future development of NIDDM is today the aim of many investigations. The absence or presence of several factors such as glycemia during pregnancy and post partum, the need for insulin treatment, disorders of the pancreatic insulin secretion, the number of pregnancies, maternal obesity, the early diagnosis of GDM, the family history of diabetes mellitus, the race and immune disorders give rise to a very high relative risk (RR) of developing NIDDM. To know the degree of risk will allow a future appropriate clinical intervention to reduce the incidence of NIDDM and its economic cost.

[Thyrotoxic periodic paralysis: an exceptional case report in Spanish population]. / Parálisis periódica tirotóxica: una observación excepcional en nuestro medio.

Thyrotoxic periodic paralysis is a rare clinical manifestation of thyrotoxicosis in spanish population. Patients show weakness and frecuently, paralysis and low levels of potassium in serum. The episode can be triggered by eating high carbohydrate diet, exercise, stress and some drugs. We present a new case of thyrotoxic periodic paralysis in a Grave's disease patient. Only four cases have been reported in the spanish literature. We conclude that a functional evaluation of thyroid gland is necessary in thyrotoxic periodic paralysis patients.

Male pseudohermaphroditism with 5-alpha-reductase deficiency: report of two new familial cases. The importance of early diagnosis.

We report two new familial cases of male pseudohermaphroditism due to 5-alpha-reductase deficiency, from the south of Spain. They were born with ambiguous genitalia and were reared as females. At the time of puberty, both brothers virilized partially and underwent a change of gender role from female to male with a stormy psychic readjustment period. We stress the value of the prolonged chorionic gonadotropin test for an early diagnosis.