Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes.

AIM: This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. METHODS: This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53 mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia-defined by a 4% oxyhaemoglobin desaturation index ≥15-was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. RESULTS: Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7 mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P=0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06-5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13-5.34, model adjusted for waist-to-height ratio). CONCLUSION: Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.

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.

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.

Abordaje integral del síndrome de Prader-Willi en la edad adulta / Overall management of Prader-Willi syndrome in adulthood

El síndrome de Prader-Willi (SPW) es un trastorno genético con hallazgos que cambian con la edad. Se caracteriza en la infancia por hipotonía, dificultades para la alimentación, retraso en el desarrollo e hipoplasia genital. En la adolescencia y la edad adulta, la problemática se centra en las alteraciones del comportamiento, la ausencia de saciedad y el retraso mental leve o moderado. En las últimas 2 décadas ha habido progresos remarcables en el conocimiento de sus manifestaciones clínicas y su historia natural, y se han desarrollado tratamientos, como la hormona de crecimiento y los psicofármacos, que han permitido una mejoría de la calidad de vida; sin embargo, los conocimientos acerca de su tratamiento en la edad adulta siguen siendo insuficientes. Este artículo quiere proporcionar una visión global de los problemas clínicos más importantes en el síndrome de Prader-Willi en la edad adulta. Los temas incluidos son la obesidad y sus consecuencias, los factores de riesgo cardiovascular y la diabetes, los problemas respiratorios, los trastornos del sueño, el hipogonadismo, la osteoporosis y los trastornos del comportamiento y psiquiátricos

Prader-Willi Syndrome (PWS) is a genetic disorder with features that change with age. In infancy, PWS is characterized by hypotonia, feeding difficulties, developmental delay, and genital hypoplasia. In adolescence and adulthood, problems are centered on behavioral disorders, absence of satiety, and mild to moderate mental retardation. In the past two decades remarkable progress has been made in the understanding of its clinical manifestations and natural history, and treatments have been developed, such as growth hormone therapy and the use of psychoactive drugs, which can improve quality of life in these patients. However, knowledge about the management of PWS in adulthood is still poor. This article aims to provide an overall view of the most important clinical problems in adults with PWS. The issues included are obesity and its consequences, cardiovascular risk factors and diabetes, respiratory abnormalities, sleep disorders, hypogonadism, osteoporosis, and behavioral and psychiatric disorders

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)