Impaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetes.

AIM: This study investigated the relationship between endothelial dysfunction (ED) and arterial stiffness (AS) in adults with type 1 diabetes and no clinical cardiovascular (CV) disease. METHODS: A total of 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects were evaluated. ED was assessed by reactive hyperaemia peripheral arterial tonometry (RH-PAT) and by serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin. AS was assessed by aortic pulse wave velocity (aPWV). All statistical analyses were stratified by gender. RESULTS: Adults with type 1 diabetes had RH-PAT index scores similar to those of their matching controls [men: 1.55 (1.38-1.98)% versus 1.61 (1.40-2.17)%, P=0.556; women: 2.07 (1.55-2.31)% versus 2.08 (1.79-2.49)%; P=0.215]. However, after adjusting for potential confounders, type 1 diabetes emerged as the main determinant of the RH-PAT index in women. Also, differences between genders in both the controls and type 1 diabetes patients disappeared. Men with diabetes had higher serum concentrations of E-selectin, and women had higher serum concentrations of sICAM-1, sVCAM-1 and E-selectin than their respective controls. However, after adjusting for potential confounders, only the differences in sICAM-1 (women) and E-selectin (both genders) remained significant. No association was found between aPWV and the RH-PAT index and ED markers after adjusting for CV risk factors. CONCLUSION: ED was increased in adults with type 1 diabetes compared with age-matched non-diabetic subjects. Also, gender differences in ED were lost in type 1 diabetes. However, ED was not associated with AS after adjusting for potential confounders. These findings suggest that ED occurs earlier than AS in type 1 diabetes.

Insulin resistance, low-grade inflammation and type 1 diabetes mellitus.

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate-eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118-125) vs. 114 (108-120) mmHg; P = 0.01] and diastolic [73 (66-80) vs. 67 (70-73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1-9.9) vs. 7.5 (7.2-8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61-3.20) vs. 0.49 (0.31-0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.

Fasting plasma peptide YY concentrations are increased in patients with major depression who associate weight loss.

BACKGROUND: Many patients with major depression refer a decreased appetite and weight loss among their symptoms. Peptide YY (PYY) and ghrelin belong to the family of peptides of the gut-brain axis implicated in the regulation of appetite and energy metabolism. PYY stimulates a powerful central satiety response and ghrelin increases food intake and weight gain. Brain-derived neurotrophic factor (BDNF) also contributes to the central control of food intake as an anorexigenic factor. AIM: To study fasting plasma total and acylated ghrelin, plasma PYY and serum BDNF levels in patients with major depression with weight loss as one of their symptoms and compare them with matched healthy controls. SUBJECTS AND METHODS: Fifteen adult patients, 9 male and 6 female, with recent diagnosis of major depression, and 16 healthy adult subjects, matched by age and anthropometric parameters were studied. All depressed patients referred weight loss and were not under antidepressant therapy. Fasting total PYY, total ghrelin and acylated ghrelin and BDNF were determined. RESULTS: Fasting total PYY was higher in patients than controls (2.01±0.09 vs 1.29±0.16 pmol/l). There were no differences in fasting total ghrelin, acylated ghrelin or BDNF levels. CONCLUSIONS: Major depressed patients, with weight loss at diagnosis, showed higher fasting plasma PYY levels that could contribute to their reduced appetite.

Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue.

CONTEXT: LPIN1 is the phosphatidic acid phosphatase that produces 1,2-diacylglycerol, and thus it is related to the synthesis of triglycerides in the adipocyte. LPIN1 has a role in lipid synthesis and nuclear receptor coactivation, both of which may be involved in lipid homeostasis and metabolism. Among others, hypoxia and endoplasmic reticulum (ER) stress are being shown to be related to the adipose dysfunction found in human obesity. OBJECTIVE: The aim of this study was to analyze LPIN1 gene expression in human adipose tissue in parallel with several hypoxia, angiogenic, ER stress and peroxisome proliferator-activated receptor (PPAR)-related genes in human obesity. DESIGN AND PATIENTS: Gene expression was quantified in abdominal (subcutaneous and visceral) adipose tissue from 62 subjects. RESULTS: We have shown a marked association between LPIN1 and PPARalpha gene expression both in subcutaneous and visceral adipose tissues. Similarly, a strong interdependence with vascular endothelial growth factor (VEGF) gene expression was also described; in fact, LPIN1 and VEGF expression levels were significantly decreased with obesity to a similar extent. CONCLUSION: These associations might suggest a possible role of LPIN1 in stress conditions that occur in chronic obesity and underlie insulin resistance.

Circulating and adipose tissue gene expression of zinc-alpha2-glycoprotein in obesity: its relationship with adipokine and lipolytic gene markers in subcutaneous and visceral fat.

CONTEXT: Zinc-alpha2-glycoprotein (ZAG) is a soluble protein similar to the class I major histocompatibility complex heavy chain, which has been implicated in lipid catabolism. We hypothesized that ZAG mRNA expression in adipose tissue may be linked with lipolytic and adipokine gene expression and have a close relationship with clinical phenotype. OBJECTIVES: The objective of the study was to analyze ZAG gene expression in human adipose tissue from lean and obese subjects. ZAG circulating plasma levels and its relationship with cardiometabolic risk factors were also studied. DESIGN: Seventy-three Caucasian (43 male and 30 female) subjects were included. Plasma and adipose tissue [sc (SAT) and visceral (VAT)] from the same patient were studied. mRNA of PPARgamma, hormone-sensitive lipase (HSL), adipose triglyceride lipase, adiponectin, omentin, visfatin, and ZAG were quantified. Plasma concentrations of ZAG were determined with ELISA. RESULTS: ZAG plasma levels showed a negative correlation with insulin (r = -0.39; P = 0.008) and the homeostasis model assessment for insulin resistance index (r = -0.36; P = 0.016). No differences in ZAG circulating levels according to body mass index classification were observed. ZAG expression in SAT was significantly reduced in overweight and obese individuals compared with lean subjects (P < 0.001 and P = 0.007, respectively). ZAG mRNA expression in both SAT and VAT depots were negatively correlated with many clinical and metabolic cardiovascular risk factors. After multiple linear regression analysis, SAT ZAG was mainly predicted by adiponectin mRNA expression (B = 0.993; P < 0.0001) and plasma triglyceride levels (B = -0.565; P = 0.006). VAT ZAG expression was predicted by adiponectin expression (B = 0.449; P < 0.0001), and HSL VAT expression (B = 0.180; P = 0.023). CONCLUSIONS: The present study provides evidence of a role of ZAG gene in adipose tissue metabolism, with a close association with adiponectin gene expression in sc and visceral fat.

Plasma visfatin concentrations increase in both hyper and hypothyroid subjects after normalization of thyroid function and are not related to insulin resistance, anthropometric or inflammatory parameters.

OBJECTIVE: The objective of this study was to evaluate plasma visfatin levels in thyroid dysfunction and its relationship with inflammatory, anthropometric and insulin resistance parameters. DESIGN AND PATIENTS: Twenty-four hyperthyroid and 27 hypothyroid patients were studied before and after treatment. Forty-five euthyroid subjects were used as control group. MEASUREMENTS: Fasting plasma visfatin, IL-6, C reactive protein, adiponectin, thyroid hormones, waist-to-hip ratio, BMI, percentage of body fat and homeostasis model insulin resistance index (HOMA-IR) were measured. RESULTS: Hyperthyroid patients showed increased insulin resistance, IL-6 and visfatin levels compared with controls (3.21 +/- 3.0 vs. 1.67 +/- 0.75, P = 0.022; 3.35 +/- 0.41 vs. 2.10 +/- 0.25 pg/ml, P = 0.016; and 37.4 +/- 5.81 vs. 23.79 +/- 4.2 ng/ml, P = 0.061 respectively). After normalization of thyroid function, IL-6 levels and HOMA-IR decreased (2.35 +/- 0.37 vs. 2.10 +/- 0.25 pg/ml, P = 0.045 and 3.21 +/- 0.60 vs. 2.28 +/- 0.38, P = 0.032 respectively), while body weight, adiposity and visfatin levels increased (26.1 +/- 1.2 vs. 26.7 +/- 1.2 kg/m(2), P = 0.049; 30.9 +/- 1.6 vs. 32.2 +/- 1.6%, P = 0.007; and 37.4 +/- 5.81 vs. 63.13 +/- 8.72 ng/ml, P = 0.047 respectively). C reactive protein and adiponectin levels were similar to those of the control group. Hypothyroid patients showed high visfatin levels (40.59 +/- 3.07 vs. 29.34 +/- 4.9 ng/ml, P = 0.049) that increased after treatment (81.4 +/- 9.2 ng/ml, P = 0.001) without changes in anthropometric or insulin resistance parameters. C reactive protein, IL-6 and adiponectin levels were similar to those of the control group. No correlations between visfatin and any analysed parameter were found in either hyper- or hypothyroidism. CONCLUSION: Visfatin exhibits a marked increase after normalization of thyroid function in both hyper and hypothyroid patients. We suggest that visfatin may play a role in the hormone stabilization process independent of anthropometric, inflammatory or insulin resistance variables.

Adult subjects with Prader-Willi syndrome show more low-grade systemic inflammation than matched obese subjects.

AIM: Adult subjects with Prader-Willi syndrome (PWS) may show several conditions that are associated with an activation of innate immunity such as obesity, deficient GH secretion or hypogonadism. Our aim was to study whether obese adult PWS subjects show an additional low-grade systemic inflammation (LGSI) in relation to obese adult non-PWS subjects and lean healthy control subjects before and after a standardized liquid meal. METHODS: Seven obese adult PWS subjects, 7 matched obese non-PWS subjects and 7 lean healthy control subjects were studied for 6 h from the administration of a standard liquid meal. RESULTS: Compared to non-PWS, PWS subjects showed higher plasma concentrations of C-reactive protein (CRP) (p=0.030), complement component C3 (p=0.018), interleukin(IL)-18 (p=0.048), and IL-6 (p=0.041) that persisted post-prandially elevated for CRP (p<0.0001), C3 (p=0.015), and IL-18 (p=0.003). Tumor necrosis factor(TNF)-alpha did not differ between the 3 groups. These results were independent from IGF-I levels, homeostasis model assessment index, and body mass index (BMI). In male subjects with PWS, testosterone levels correlated to IL-18 (r=-0,646, p=0.041). CONCLUSIONS: Compared to matched non-PWS subjects, the obese PWS subjects in this study showed an additional LGSI that persisted postprandially and was independent from BMI, insulin resistance, and deficient GH secretion. However, in PWS males, high IL-18 levels were related to low testosterone concentrations.

Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres.

AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. CONCLUSIONS: Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus.

Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus. The presence of vitamin D receptors (VDR) and vitamin D-binding proteins (DBP) in pancreatic tissue and the relationship between certain allelic variations in the VDR and DBP genes with glucose tolerance and insulin secretion have further supported this hypothesis. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but also through a direct action on pancreatic beta-cell function. Therefore, owing to its increasing relevance, this review focuses on the role of vitamin D in the pathogenesis of type 2 diabetes mellitus.

Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes.

BACKGROUND: It has been speculated that oral hypoglycaemic agents that block K-ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. DESIGN: A multicentre, double-blind, placebo-controlled, randomized trial was conducted in 109 drug-naive 30- to 75-year-old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C-peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)-B% (as surrogate of beta-cell activity) and HOMA-S% (as surrogate of insulin sensitivity). RESULTS: At the end of the follow-up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6.7 +/- 0.6 vs. 7.2 +/- 0.7%, respectively; P < 0.001), fasting plasma glucose (7.9 +/- 2.1 vs. 8.5 +/- 2.0 mmol L(-1); P = 0.023) and systolic blood pressure (125.3 +/- 15.4 vs. 129.3 +/- 18.7 mmHg; P = 0.015), and higher values of HOMA-B%[75.7 (51.8-99.4) vs. 57.7 (42.2-83.4); P = 0.033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0.355, P = 0.011). CONCLUSIONS: In drug-naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.

Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes.

OBJECTIVE: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. DESIGN: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. METHODS: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor alpha receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. RESULTS: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (r=-0.244, P=0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; r=-0.231, P=0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. CONCLUSIONS: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.

Increased cholesterol intake in women with gestational diabetes mellitus.

AIM: Cholesterol intake is associated with the risk for type 2 diabetes mellitus, but no previous studies have evaluated its role regarding the risk of gestational diabetes mellitus (GDM). We investigate the relation between cholesterol intake and GDM. METHODS: At screening for GDM, 335 pregnant women were evaluated for dietary intake (including cholesterol) during the previous year (validated food-frequency questionnaire). RESULTS: Forty-one women were diagnosed with GDM and 294 did not meet the GDM criteria. Women with GDM were older (32.8+/-0.7 vs. 30.2+/-0.3 years; P=0.01) and had a higher body mass index (27.3+/-0.7 vs. 24.3+/-0.3 kg/m2; P=0.01) than women without GDM. They also had more frequently a family history of type 2 diabetes mellitus (51.2% vs. 40.0%; P=0.02) and history of previous GDM (14.6% vs. 1.7%; P=0.01), and were evaluated earlier in pregnancy (22.1+/-1.2 vs. 24.9+/-0.5 weeks; P=0.03). There were no significant differences between groups in smoking habit, and alcohol, total energy, protein, carbohydrate, fats and fiber intake. Women with GDM had a higher cholesterol intake than women without GDM (145.3+/-4.5 mg/1000 kcal vs. 134.5+/-1.6 mg/1000 kcal; P=0.03). In a multiple logistic regression model, previous GDM, BMI, age and cholesterol intake (OR=1.88; 95% CI: 1.09-3.23 for each increase of 50 mg/1000 kcal) were independently and positively associated with GDM. CONCLUSION: We conclude that cholesterol intake is independently associated with GDM and that it could be involved in the pathogenesis of GDM.

Utilidad de la resonancia nuclear magnética en las lesiones del pie diabético / NMR usefulness in the diabetic foot

Los individuos con diabetes mellitus presentan a menudo complicaciones en el pie conocidas como "pie diabético". La evaluación clínica de los pacientes es fundamental, aunque a menudo insuficiente, para la valoración de las lesiones que presenta el pie diabético. En los últimos años, la resonancia nuclear magnética (RNM) se está revelando como una técnica complementaria útil en la evaluación de estas complicaciones, entre las que se encuentran ulceraciones o procesos infecciosos de partes blandas (celulitis,abscesos) o articulares (artritis sépticas), hasta osteomielitis oneuroartropatia de Charcot. El diagnóstico diferencial entre osteomielitis y neuroartropatia de Charcot puede ser particularmente complejo, y en esta situación, la RNM puede proporcionar información sumamente útil (distribución de la lesiones, patrón de edema, señales postcontraste, presencia de deformidades, afectación de partes blandas), con las que se debe estar familiarizado para realizar un diagnóstico adecuado

Diabetic foot is a frequent complication of diabetes mellitus. In the assessment of the diabetic foot clinical examination is mandatory, although frequently it is insufficient for a proper diagnosis. In the last years, nuclear magnetic resonance (NMR) has became an useful complementary diagnostic tecnique in the evaluation of the complications of the diabetic foot. NNR provides useful informationin the evaluation of ulcerations, infectious conditions (cellulitis, abscess, septic arthritis, osteomyelitis) and Charcot’s neuroarthropathy. Among these complications, the differential diagnosis between osteomyelitis and Charcot’s neuroarthropathy is often difficult and of main importance. In this issue, information provided by NMR on location of the lesions, pattern of edema, postcontrast signals, deformities and soft tissue involvement is of importance for a right differential diagnosis

Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus.

OBJECTIVE: The development of diabetic neuropathy (DN) is predicted by cardiovascular risk factors associated with insulin resistance. As inflammation seems to be implicated in the pathogenesis of insulin resistance, we investigated whether subjects with type 1 diabetes mellitus (T1DM) and DN have an increase in plasma concentrations of inflammatory proteins involved in insulin resistance. DESIGN: Cross-sectional. Patients One hundred twenty subjects, all diagnosed with T1DM 14 years before. MEASUREMENTS: (1) Sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) DN (peripheral and cardiac autonomic), retinopathy and nephropathy; (3) plasma concentrations of soluble fractions of tumour necrosis factor alpha receptors 1 and 2 (sTNFR1 and sTNFR2), interleukin-6, high-sensitive C-reactive protein, adiponectin and leptin; and (4) insulin resistance (by way of a mathematical estimation of the glucose disposal rate - eGDR-). RESULTS: Thirty-six subjects had DN and 84 did not. Subjects with DN received higher insulin doses (57.6 +/- 16.7 vs. 49.2 +/- 15.0 IU/day; P = 0.008) and had higher WHR (0.85 +/- 0.07 vs. 0.81 +/- 0.10; P = 0.007) and HbA1c values (8.5 (7.6-9.6) vs. 7.7 (7.3-8.9)%; P = 0.049) than subjects without DN. They also had higher values of sTNFR1 (2.42 +/- 0.60 vs. 1.96 +/- 0.66 microg/l; P = 0.001) and sTNFR2 (4.73 +/- 1.33 vs. 4.14 +/- 1.09 microg/l; P = 0.015), and were more insulin resistant (eGDR values: 7.28 (5.83-8.03) vs. 8.30 (7.17-9.03) mg kg(-1) min(-1); P = 0.003). The relationship between DN and either sTNFR1 or sTNFR2 remained essentially unchanged after adjusting for several confounders, including glycaemic control, WHR, lipid profile, blood pressure and other microvascular complications (OR for sTNFR1: 2.592 (1.222-5.498), P = 0.013; OR for sTNFR2: 2.124 (1.258-3.587), P = 0.005). CONCLUSIONS: The activity of the TNF-alpha system is increased in subjects with type 1 diabetes mellitus and diabetic neuropathy, regardless of their glycaemic control and cardiovascular risk factors associated with insulin resistance. These results suggest that TNF-alpha may play a pathogenic role in the development of diabetic neuropathy.

The tumour necrosis factor (TNF)-alpha system is activated in accordance with pulse pressure in normotensive subjects with type 1 diabetes mellitus.

OBJECTIVE: Pulse pressure (PP) and inflammation are important predictors of cardiovascular disease (CVD), even in the normotensive. The age-related increase in PP can be diagnosed up to 20 years earlier in subjects with type 1 diabetes mellitus (T1DM) than in the general population. Some evidence suggests that PP can stimulate inflammation. Our aim was to study the relationship between PP and plasma inflammatory proteins in normotensive subjects with T1DM. DESIGN: This was a cross-sectional study of a group of normotensive (<140/80 mmHg) subjects diagnosed with T1DM 14 years before. None of them had clinically proven CVD or inflammatory conditions or were on antiplatelet, antihypertensive, anti-inflammatory or lipid-lowering treatment. METHODS: The following information was recorded: sex, age, body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), PP, mean blood pressure (MBP), smoking, alcohol intake, insulin dose, lipid profile, HbA1c, microvascular complications, and plasma concentrations of soluble receptor types 1 and 2 of tumour necrosis factor (TNF)-alpha (sTNFR1 and sTNFR2, respectively), interleukin-6, C-reactive protein, adiponectin and leptin. RESULTS: A total of 112 subjects were evaluated (aged 27.4+/-6.6 years, 52.7% women, BMI: 20.4+/-2.7 kg/m2, WHR: 0.82+/-0.09, SBP: 112+/-12 mmHg, DBP: 68+/-9 mmHg, PP: 45+/-9 mmHg, MBP: 82+/-9 mmHg, HbA1c: 8.2% (7.3-9.0%), 41.1% microvascular complications). After adjusting for potential confounders, only inflammatory markers of the TNF-alpha system correlated significantly with PP (Pearson correlation coefficient between sTNFR1 and PP: r = 0.215, P = 0.030; and between PP and sTNFR2: r = 0.238, P = 0.020). CONCLUSION: In normotensive subjects with T1DM after 14 years of diagnosis, the activation of the TNF-alpha system is positively associated with PP levels. This finding might suggest a pathogenic role of the TNF-alpha system in the development of cardiovascular disease in T1DM.

Dissemination of 'patient-oriented evidence that matters' on the Internet: the case of Type 2 diabetes treatment.

AIMS: To evaluate the dissemination of patient-oriented evidence that matters (POEMs) derived from the UK Prospective Diabetes Study (UKPDS) through health information websites. METHODS: Google and Altavista search engines were used to generate a list of websites about Type 2 diabetes treatments. We evaluated a random sample of 50 websites from each list, plus the first 10 websites displayed on each search engine looking for the presence of POEMs about diabetes treatment derived from the UKPDS. Websites were also ranked using the DISCERN instrument. RESULTS: The final sample consisted of 66 websites. The most frequently stated item was that tight blood pressure decreased complications and/or mortality (55.5%). The effects of metformin on morbidity and/or mortality in overweight patients and the greater effect of control of blood pressure rather than blood glucose control on complications were stated in 18.2 and 16.7% of cases, whereas the lack of effect of tight blood glucose control on premature mortality and of insulin or sulphonylureas on aggregate micro- or macrovascular outcomes in overweight patients were stated in one case each (1.5%). The lack of effect of tight blood glucose control on quality of life was not stated in any website. POEMs were more frequently present in websites rated high with the DISCERN instrument, websites with the Health-on-the-Net seal and non-commercial websites. CONCLUSIONS: The dissemination of POEMs through the Internet is poor. If patients are to be involved in decision-making processes, efforts should be made to update the Internet contents to meet this challenge.

[Evaluation of the process and the outcomes of care for the diabetic patients in a hospital]. / Evaluación del proceso y los resultados de la atención a los pacientes diabéticos en un hospital.

For the purpose of establishing a specific information system in order to identify the diabetic patients looked after in the hospital and evaluate the processes and the clinical outcomes obtained, a prospective descriptive study was designed--in the Corporació Parc Taulí of Sabadell (Barcelona)--about the diabetic patients cared starting in January 1998, through a clinical registry and other hospital sources of information. Seven hundred and fifty-five patients were identified, and the completeness of the registry was 98%. It was feasible the integration of the registry of admissions with that of the laboratory, that of the discharges from hospital, that of pharmacy and the specific clinical registry. An evaluation of the glycemic control was made in around 90% of the patients, and the registry of the organic explorations was higher than 87%. Although it was not possible in this study, the incorporation of the information from the primary care would complete the follow-up of the patients.

Translation of the recommendations for the diagnosis of diabetes mellitus into daily clinical practice in a primary health care setting.

AIMS: to assess the implementation of 1985 recommendations for the diagnosis of diabetes (World Health Organization [WHO]) in a primary care setting, and the physician's attitude toward the diagnosis of diabetes mellitus (DM). MATERIAL AND METHODS: Subjects with a fasting plasma glucose (FPG)>6.1 mmol/l (> or =110 mg/dl) and with previously unknown glucose tolerance status were identified retrospectively in a primary health care center during a 45-month period. The following variables were evaluated: anthropometric parameters, fasting plasma glucose and oral glucose tolerance test (OGTT) values, registration of a diagnosis of diabetes in clinical records, smoking status, lipid profile and blood pressure. RESULTS: 1181 subjects with a FPG>6.1 mmol/l were identified (target population): 171 with a FPG>7.8 mmol/l and 1010 with a FPG between 6.1 and 7.7 mmol/l. In the latter group, an OGTT was performed in 553 subjects (54.8%) (173 yielded a diagnosis of diabetes). During the study period, diabetes was diagnosed in 29.1% (n=344) of the target population. Following the 1985 WHO recommendations, a confirmatory diagnostic test was repeated in 92 (69.7%) subjects with a FPG between 7.8 and 11.0 mmol/l, and in 132 subjects (23.87%) who had already received an initial OGTT. The analysis of the diagnostic process followed by the different physicians revealed a high interindividual variability in terms of: proportion of cases diagnosed as diabetes by an OGTT (from 35.7 to 65.2), percentage of subjects with a FPG 6.1-7.7 mmol/l without an OGTT (7.33-70.27%), proportion of confirmatory OGTTs (0-57.89%), and percentage of misdiagnosed cases (1.16-6.34%). The percentage of subjects misdiagnosed was negatively correlated with the proportion of OGTT repetitions. CONCLUSIONS: 1985 WHO recommendations for the diagnosis of diabetes are only partially followed at a primary health care level. There is a high interindividual variability among physicians in the implementation of these recommendations that is associated with the misdiagnosis of diabetes.

Evaluación del proceso y los resultados de la atencióna los pacientes diabéticos en un hospital* / Evaluation of the process and the outcomes of care for the diabetic patients in a hospital

Con el fin de establecer un sistema de información específico para identificar a los pacientes diabéticos atendidos en el hospital y evaluar los procesos y los resultados clínicos obtenidos se diseñó un estudio descriptivo prospectivo en la Corporació Parc Taulí de Sabadell (Barcelona) de los pacientes diabéticos atendidos a partir de enero de 1998 mediante un registro clínico y otras fuentes de información hospitalarias. Se identificaron 755 pacientes siendo la exhaustividad del registro del 98 por ciento. Fue factible la integración del registro de admisiones con el de laboratorio, las altas hospitalarias, el de farmacia y el registro clínico específico. Se realizó una evaluación del control glucémico en alrededor del 90 por ciento de los pacientes y el registro de las exploraciones orgánicas fue superior al 87 por ciento. Aunque no fue posible en este proyecto, la incorporación de la información procedente de la asistencia primaria completaría el seguimiento de los pacientes (AU)