Physical activity patterns in type 1 diabetes in Spain: The SED1 study.

AIMS: To describe the physical activity (PA) frequency and intensity in the Spanish type 1 diabetes mellitus (T1D) population and its association with their glycemic control. METHODS: A cross-sectional observational study was carried out in 75 Spanish public hospitals (the SED1 study). T1D patients over 14years of age self-completed the International Physical Activity Questionnaire (IPAQ) to determine their level of exercise. The relationship between PA frequency and intensity in T1D patients and glycemic control and the diabetes therapeutic education received were analyzed. RESULTS: A total of 592 patients were evaluable. A 6.8% of the sample performed light PA, 20.9% moderate and 72.3% vigorous. Estimated PA presented a high inter-individual variability. Men consumed more energy (METS) than women, these differences being more noticeable in vigorous METS (2865.80 in men vs 1352.12 in women). Women invested more min/week in the domestic and garden area (639.03 vs 344.39, p = 0,022). A correlation between glycemic control and the METs was not observed. CONCLUSIONS: The Spanish T1D population performed PA in a higher frequency and intensity than the general population. A relationship between PA and glycemic control couldn´t be shown. However, limitations of the study should be kept in mind to discard a long-term positive influence.

Steno type 1 risk engine and preclinical atherosclerosis in Mediterranean individuals with type 1 diabetes.

BACKGROUND AND AIMS: Tools to detect type 1 diabetes (T1D) individuals at overt cardiovascular disease (CVD) risk are scarce. We aimed to assess the usefulness of the score 'Steno Type 1 Risk Engine' (Steno-Risk) to identify T1D patients with advanced carotid atherosclerosis. MATERIAL AND METHODS: T1D patients without CVD with at least one of the following were included: ≥40 years, diabetic nephropathy, or diabetes duration ≥10 years with ≥1 CVD risk factor. Intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by standardized B-mode ultrasonography. Steno-Risk was used to estimate 10-year risk (<10% low; 10%-20% moderate; ≥20% high risk). Associations between Steno-Risk and preclinical atherosclerosis were assessed after adjusting for other CVD risk factors. RESULTS: We evaluated 302 patients (55% men, age 47.8 ± 9.8 years, T1D duration 26.3 ± 9.3 years). The prevalence of carotid plaque and ≥2 plaques were 36.4% and 19.2%, respectively; without sex differences. Age (57.4 ± 7.4 vs 37.1 ± 6.2 years), T1D duration (31.3 ± 10.4 vs 21.5 ± 7.1 years), hypertension (52.3% vs 6.3%), nephropathy (25.6% vs 5.1%) and retinopathy (53.5% vs 32.9%) were higher in high-risk (n = 86) vs low-risk participants (n = 79; P < .001 for all). Preclinical atherosclerosis (IMT and plaque) increased in parallel with Steno-Risk (P < .001). In logistic regression analysis, both age ≥40 years and Steno-Risk ≥20% were associated with the presence of plaque (OR 4.22 [1.57-11.36] and 3.79 [1.61-6.80]; respectively), but only high Steno-Risk remained independently associated with ≥2 plaques (OR 3.31 [1.61-6.80]). CONCLUSION: Steno-Risk is independently associated with preclinical atherosclerosis. Further studies are needed to ascertain its usefulness in this high-risk population.

Long-term outcome of insulin pump therapy: reduction of hypoglycaemia and impact on glycaemic control.

AIMS: To determine the long-term outcome of continuous subcutaneous insulin infusion (CSII) in Type 1 diabetes according to Catalan National Health Service indications. METHODS: Retrospective observational study including 178 patients with Type 1 diabetes who started CSII treatment in our centre (2003-2008). All patients were followed in our CSII programme for outpatients for at least 5 years. Data on annual HbA1c levels were collected, and the main indication for starting CSII was analysed. RESULTS: Twenty-seven of 178 patients were excluded because of loss to follow-up or withdrawal from CSII, thus 151 patients (aged 37.4 ± 10.5 years, 64% women) were analysed. The main indications for starting CSII were suboptimal metabolic control (60.9%), severe hypoglycaemia/hypoglycaemia unawareness (25.5%) and others (13.6%). HbA1c was 64 ± 13 mmol/mol (8.0 ± 1.2%) at the start of CSII and 62 ± 13 mmol/mol (7.8 ± 1.2%) after 5 years in the total cohort (P = 0.1). The severe hypoglycaemia rates were 0.66 ± 1.61 and 0.17 ± 0.42 episodes/patient/year (P < 0.001). In patients with suboptimal metabolic control, HbA1c decreased from 68 ± 12 mmol/mol (8.4 ± 1.1%) to 64 ± 14 mmol/mol (8.0 ± 1.3%) (P = 0.016), with 37.4% of those in this group having an HbA1c ≤ 58 mmol/mol (7.5%) after 5 years. In patients starting CSII due to severe hypoglycaemia the problem was considered resolved in 93%, and in 64% of those starting CSII because of suboptimal glycaemic control, HbA1c improved significantly. CONCLUSIONS: CSII therapy achieves and maintains its efficacy mainly in terms of reducing severe hypoglycaemia. In the whole group of patients, the reduction in HbA1c is transient and disappears after 5 years.

Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial.

AIMS: To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. METHODS: After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels ≥8.0% and ≤12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. RESULTS: The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 ± 1.2% vs -0.4 ± 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. CONCLUSIONS: Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes.

Successful Pancreas Transplantation From a Deceased Donor Intoxicated With Oral Antidiabetic Agent: A Case Report.

Simultaneous kidney pancreas transplantation (SKP) is a common procedure for the patient with long-term type 1 diabetes mellitus (DM) with terminal renal failure. It is unusual to consider the pancreas from a deceased donor who died after an acute intoxication with oral antidiabetic agent (OAA), which would suggest an abnormal functionality of the organ and preclude the potential use of the graft. We present a case of a successful pancreatic transplantation from a donor who died of acute cerebral edema secondary to severe hypoglycemia induced by OAA acute intoxication.

Impact of continuous glucose monitoring on quality of life, treatment satisfaction, and use of medical care resources: analyses from the SWITCH study.

To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (n = 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children's HRQOL or parents' proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children's caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (P = 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.

Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

AIM: Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials. METHODS: EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ≥ 3% increase in body weight. RESULTS: In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data. CONCLUSION: EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. METHODS: Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. RESULTS: Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). CONCLUSIONS/INTERPRETATION: Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.

Adding questions about cardiovascular risk factors improve the ability of the ADA questionnaire to identify unknown diabetic patients in Spain

Introduction: Currently, there are not specific questionnaires for Spanish population to identify people at risk of undiagnosed diabetes. When American Diabetes Association (ADA) test is validated in the Spanish population, the sensitivity and specificity values obtained are lower than those found in the USA. Objectives: To develop a screening tool based on the ADA questionnaire, to prospectively identify undiagnosed type 2 diabetes in Spanish ambulatory patients. Methods: Epidemiological, transversal, multicentre study, including 2,662 ambulatory patients of Primary Care centres, mean age (SD) 61.7 (10.2) years (53% women), needing a blood test and attending follow-up protocols for chronic pathologies or periodic screening programs. Classification tree construction was achieved through classical and Artificial Intelligence (AI) methods. The sensitivity, specificity, and the positive and negative predictive values were described and compared with the ADA questionnaire. Results: The final selected classification tree included the following variables: previous impaired fasting glucose or glucose intolerance; recent weight gain; parents, siblings or children with diabetes; smoking habit and pharmacologic treatment for lipid disorders (sensitivity: 80.7%; specificity: 70.9%; positive predictive value: 45.3%; negative predictive value: 92.5%). This tree showed a better Receiver Operating Characteristic curve than that of the ADA test (sensitivity: 84.3%; specificity: 20.9%). Conclusions: The inclusion of questions regarding lipid disorders, smoking habit and weight gain increase the specificity of the ADA test to identify undiagnosed type 2 diabetes in Spanish patients older than 45 years (AU)

Quality of life outcomes in subjects with type 1 diabetes with and without repeated hypoglycaemia. Short-term results of CSII treatment

Objectives: To evaluate quality of life (QoL) characteristics and outcomesin subjects with T1D with and without non-severe (NSH)/severehypoglycaemia (SH) as a main indication for CSII. Patientsand methods: Two groups of T1D subjects were selected fromcandidates to CSII following the criteria of the Catalan National HealthService. Twenty-one subjects (aged 34.6±7.5 years; 13 women) inwhom CSII was started because of recurrent NSH and SH) were included(H Group). They were compared to 18 T1D subjects (aged32.3±10.1 years; 14 women) in whom CSII was initiated becauseof non-optimal control without repeated NSH/SH (NH group). Generalcharacteristics, metabolic control and QoL/health state (DQoL/SF-12 questionnaires) were evaluated (baseline/after 12-months).Results: In the H group, the number of NSH/week diminished from5.01±1.56 (baseline) to 2.76±1.09 after 12 months (p <0.001).SH diminished from 1.24±0.62 per subject year (baseline) to0.12±0.21 (12 months, p <0.001). There were no differences inA1c (6.9±1.3 vs 6.5±0.8%; NH and H) after 12-months of CSII.The H group scored better in DQoL-impact of treatment subscale atbaseline (45.7±7.0 vs 33.7±7.3; p <0.001, NH and H). QoL improvedsimilarly after 12 months in both groups, but the differencein DQoL-impact of treatment (41.5±8.5 vs 31.0±5.8; p <0.001)was maintained. Conclusions: CSII improves QoL independently ofits main indication. Subjects who initiate CSII because of repeatedhypoglycaemic episodes display a different QoL perception thanthose without this indication when starting this therapy. Although thisfinding does not preclude favorable results, probably it has to beconsidered in order to encourage patients to start this modality oftreatment(AU)

Phenotype changes at the onset of type 1 diabetes in young adults from a mediterranean area throughout the last decade.

The Accelerator hypothesis postulates that Type 1 Diabetes (T1D) and Type 2 Diabetes are mostly the same disorder. Till now, the data testing the hypothesis and the importance of BMI and insulin resistance in the development of T1D comes almost exclusively from childhood. Our study aimed to investigate changes in clinical and metabolic characteristics of young adults at diagnosis of T1D during the last decade in a Mediterranean area. Ninety-three adults (> or =18 years) with newly diagnosed T1D were evaluated from our database. Thirty-one of them were diagnosed in the period 07/1994-1995 (G95), 39 between 07/1998 and 1999 (G99) and 23 in 2003 (G03). Plasma C-peptide measurements were performed before and 6 min after intravenous injection of 1 mg of glucagon. In those subjects with a basal C-peptide > 0.2 nmol/l, insulin resistance was evaluated using the HOMA-2 model. HbAc, GAD, IA2 and insulin autoantibodies were measured. There was not a significant rise in BMI at diagnosis of T1D in young adults admitted to our Hospital. This was also the case when BMI after 4 weeks of diagnosis was considered (23.7 +/- 3.6, 23,6 +/- 2.4 and 23.4 +/- 3.3 kg/m2, G95 G99 and G03, respectively). In the entire group of subjects, we could not observed any relationship between the patients BMI and age at diagnosis. Likewise, we could not observed differences in any of the clinical, immunological or metabolic characteristics. IR was not different between groups (G95 n=18, 0.73 +/- 0.21; G99 n=29, 0.86 +/- 0.33; G3 n=13, 0.66 +/- 0.34) and was not related to the age at diagnosis. In summary, our data collected from young adults with newly diagnosed T1D from a Mediterranean area indicates that the phenotype, including BMI, at the onset of the disease has not substantially varied during the last decade. In spite of our data do not fit with the accelerator hypothesis the postulate could be of interest in a different age group.

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.

Propuesta de algoritmo terapéutico de la diabetes mellitus. Papel de la insulina / A proposed therapeutic algorithm for diabetes mellitus. The role of insulin

Actualmente, salvo contraindicaciones, el tratamiento de la diabetes mellitus tipo 1 (DM1) se basa en lo que conocemos por tratamiento intensivo con insulina. Esta modalidad incluye la utilización de insulinas de acción rápida (incluyendo análogos) con el fin de controlar los picos hiperglucémicos posprandiales e insulinas de acción intermedia o lenta (incluyendo análogos) con el objetivo de aportar unos valores basales de insulina (terapia tipo bolo/basal). Sabemos que este tipo de modalidad terapéutica va asociada a una disminución en las complicaciones crónicas micro y macrovasculares asociadas a la enfermedad. El sucesivo descenso que se ha producido en los últimos años de las cifras de hemoglobina glucosilada (HbA1c) como objetivo de control en aquellos pacientes con diabetes mellitus tipo 2 (DM2) con el fin de prevenir ambos tipos de complicaciones, ha puesto en evidencia la falta de eficacia de los antidiabéticos orales y de las estrategias utilizadas hasta la fecha. Además, nos indica que si queremos conseguir que un alto porcentaje de nuestros pacientes esté dentro de los objetivos de control glucémico, el tratamiento debe ser «agresivo» desde las fases iniciales de la enfermedad y puede requerir la utilización combinada de fármacos, incluyendo la insulina e incluso de esta última en múltiples dosis. La utilización de insulina inhalada como insulina preprandial en pacientes con DM1 y 2 ha demostrado ser tan eficaz como la insulina regular a la hora de mejorar el control metabólico con un número similar de eventos hipoglucémicos y una mejor percepción y satisfacción con el tratamiento por parte del paciente. Sin embargo, los datos de los que disponemos hasta la fecha y el coste de la insulina inhalada no hacen recomendable el uso de forma rutinaria de esta vía de administración y debería reservarse para casos específicos (AU)

Currently, except when there are contraindications, the treatment of type I diabetes is based on intensive insulin therapy. This modality includes the use of rapid action insulin (including analogs) to control postprandialhyperglycaemic peaks and intermediate and long-acting insulin (including analogs) to provide basal insulin levels (basal/bolus regimen). This type of therapeutic modality is known to decrease the chronic micro- and macrovascular complications of the disease. The decrease produced in the last few years in HbA1c levels with the aim of achieving tight control in patients with type 2 diabetes mellitus to prevent both types of complications has revealed the lack of effectiveness of oral antidiabetic agents and the strategies used to date. This decrease also indicates that, if a high percentage of patients are to achieve the objectives of glycemic control, treatment should be «aggressive» from the initial phases of the disease and may require the use of combined drugs, including insulin and even multiple-dose insulin. The use of inhaled insulin as preprandial insulin in patients with diabetes mellitus type I and type 2 has been demonstrated to be as effective as regular insulin inimproving metabolic control with a similar number of hypoglycemic events and better patient satisfaction. Nevertheless, the data available to date and the cost of inhaled insulin do not allow this route of administration to be recommended for routine use; rather, it should be reserved for specific patients (AU)

Outcome of pregnancy in women with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion or conventional therapy. A case-control study.

The aim was to evaluate and compare the outcome of pregnancies of women with type 1 diabetes (T1D) intensively treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Twenty-nine women with T1D receiving CSII during pregnancy as intensive insulin therapy (27 started CSII during pregnancy planning while 2 started CSII during the 1st month of gestation) were matched for age, duration of T1D, White's classification, BMI before gestation, parity and HbA1c before pregnancy with 29 women treated with MDI. Metabolic control and acute complications were registered including ketoacidosis and severe hypoglycaemic episodes, and the development of hypertension induced by pregnancy and pre-eclampsia. Perinatal mortality, stillbirth, minor and major congenital malformations, macrosomia, weeks at delivery, caesarean section and perinatal complications were also recorded. As expected, there were no differences between the two groups in terms of age, duration of the disease, White's classification, BMI before gestation, parity and HbA1c before pregnancy. The proportion of subjects who received preconceptional guidance and planned pregnancy did not differ between groups. No differences were observed in HbA1c, insulin dose and BMI throughout gestation in either group of patients. Maternal, foetal and perinatal outcome were similar in women treated with CSII or MDI. The use of CSII in pregestational T1D women is associated with similar results in metabolic control, maternal, foetal and perinatal outcome during pregnancy to those obtained using MDI.