Treatment patterns and glycated haemoglobin levels over 36 months in individuals with type 2 diabetes initiating second-line glucose-lowering therapy: The global DISCOVER study.

AIMS: To describe glucose-lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow-up from the start of second-line therapy. MATERIALS AND METHODS: This data analysis from the 3-year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second-line glucose-lowering therapy. Treatment and HbA1c data were collected at baseline (start of second-line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow-up were analysed using the McNemar test, with carry-forward imputation for intermediate missing values. RESULTS: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow-up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. CONCLUSIONS: Dual oral therapy was the most common treatment regimen at the start of second-line treatment, and over half of the participants remained on the same treatment during follow-up.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes.

Dapagliflozin is associated with greater reductions in HbA1c and weight than saxagliptin in management of type 2 diabetes mellitus (T2DM). The present post hoc analyses compared the durability of these effects over short- and long-term follow-up in patients with T2DM who were inadequately controlled with metformin (≥1500 mg/day) and who were receiving either dapagliflozin (10 mg/day) or saxagliptin (5 mg/day). Failure of glycaemiccontrol was assessed using the slope of the change in HbA1c from baseline-over-time regression line (coefficient of failure [CoF]). CoF was compared directly (dapagliflozin vs saxagliptin) over the short term (NCT01606007, 24 weeks) and indirectly (placebo-adjusted) over the long term (NCT00528879 and NCT00121667, 102 weeks). A low CoF value indicated greater durability. CoF was lower for dapagliflozin versus saxagliptin over 18-24 weeks (-1.38%/year; 95% CI, -2.41 to -0.35; P = .009) and 20-102 weeks (-0.37%/year; 95% CI, -0.73 to -0.02; P = .04). Fewer dapagliflozin-treated patients versus saxagliptin-treated patients required rescue medication or discontinued the study because of failure to achieve glycaemic control at 24 weeks (3.4% vs 9.4%; P = .0191). In patients with T2DM who were inadequately controlled with metformin, dapagliflozin was associated with greater durability of glycaemic control than saxagliptin over 18-24 and 20-102 weeks.

A comparative study of blood cell count in four automated hematology analyzers: An evaluation of the impact of preanalytical factors.

Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral laboratories are often used but challenged with use of different hematology platforms, variable blood shipping times and storage conditions, and the different sensitivities of specific cell types. To extend the scientific literature and knowledge on the temporal commutability of blood samples between hematology analyzers, we performed a comparative ex-vivo study using four of the most utilized commercial platforms, focusing on the assessment of eosinophils given its importance in asthma management. Whole blood from healthy volunteers with and without atopy (n = 6+6) and participants with eosinophilic asthma (n = 6) were stored under different conditions (at 4, 20, 30, and 37°C, with or without agitation) and analyzed at different time points (3, 6, 24, 48 and 72h post-sampling) in parallel on the Abbott CELL-DYN Sapphire, Beckman Coulter DxH900, Siemens ADVIA 2120i and Sysmex XN-1000V. In the same blood samples, eosinophil-derived neurotoxin (EDN), eosinophil activation and death markers were analyzed. All platforms gave comparable measurements of cell differentials on fresh blood within the same day of sampling. However, by 24 hours, significant temporal and temperature-dependent differences were observed, most markedly for eosinophils. None of the platforms performed perfectly across all temperatures tested during the 72 hours, showing that handling conditions should be optimized depending on the cell type of interest and the hematology analyzer. Neither disease status (healthy vs. asthma) nor agitation of the sample affected the cell quantification result or EDN release. The eosinophil activation markers measured by flow cytometry increased with time, were influenced by temperature, and were higher in those with asthma versus healthy participants. In conclusion, hematology analyzer, time window from sampling until analysis, and temperature conditions must be considered when analyzing blood cell differentials, particularly for eosinophils, via central labs to obtain counts comparable to the values obtained in freshly sampled blood.

Factors affecting vitamin D status in different populations in the city of São Paulo, Brazil: the São PAulo vitamin D Evaluation Study (SPADES).

BACKGROUND: Hypovitaminosis D is a common condition among elderly individuals in temperate-climate countries, with a clear seasonal variation on 25 hydroxyvitamin D [(25(OH)D] levels, increasing after summer and decreasing after winter, but there are few data from sunny countries such as Brazil. We aimed to evaluate 25-hydroxyvitamin D concentrations and its determining factors, in individuals in the city of São Paulo belonging to different age groups and presenting different sun exposure habits. METHODS: 591 people were included as follows: 177 were living in institutions (NURSING HOMES, NH, 76.2 ± 9.0 years), 243 were individuals from the community (COMMUNITY DWELLINGS, CD, 79.6 ± 5.3 years), 99 were enrolled in physical activity program designed for the elderly (PHYSICAL ACTIVITY, PA, 67.6 ± 5.4 years) and 72 were young (YOUNG, 23.9 ± 2.8 years). Ionized calcium, PTH, 25(OH)D, creatinine and albumin were evaluated. ANOVA, Mann-Whitney and Kruskal Wallis tests, Pearson Linear Correlation and Multiple Regression were used in the statistical analysis. RESULTS: 25(OH)D mean values during winter for the different groups were 36.1 ± 21.2 nmol/L (NH), 44.1 ± 24.0 nmol/L (CD), 78.9 ± 30.9 nmol/L (PA) and 69.6 ± 26.2 nmol/L (YOUNG) (p < 0.001) while during summer they were 42.1 ± 25.9 nmol/L, 59.1 ± 29.6 nmol/L, 91.6 ± 31.7 nmol/L and 103.6 ± 29.3 nmol/L, respectively (p < 0.001). The equation which predicts PTH values based on 25(OH)D concentration is PTH = 10 + 104.24.e-(vitD-12.5)/62.36 and the 25(OH)D value above which correlation with PTH is lost is 75.0 nmol/L. In a multiple regression analysis having 25(OH)D concentration as the depending variable, the determining factors were PTH, ionized calcium and month of the year (p < 0.05). CONCLUSIONS: Much lower 25(OH)D values were found for the older individuals when compared to younger individuals. This finding is possibly due to age and habit-related differences in sunlight exposure. The existence of seasonal effects on 25(OH)D concentration throughout the year was evident for all the groups studied, except for the nursing home group. According to our data, PTH values tend to plateau above 75 nmol/L.

Considerations when planning and conducting large global observational studies: Experience from the DISCOVER study of patients with type 2 diabetes.

DISCOVER is a global programme of observational research that includes patients with type 2 diabetes initiating second-line glucose-lowering therapy from 38 countries worldwide, including many with little or no previous epidemiological data available. More than 15,000 patients were followed-up for 3 years, and comprehensive data were collected using a standardized electronic case report form at enrolment, and 6, 12, 24 and 36 months. The study has formed the basis for a long-term registry that is intended to expand the geographic and clinical scope of the study and allow data collection beyond 3 years. In this review, critical aspects of study planning and implementation are summarized, along with challenges that were faced, to provide a resource for researchers planning similar studies. In particular, it is essential to set realistic expectations regarding the degree of study representativeness that can be achieved, allow for sufficient time to obtain ethics committee approval, develop tools to help recruit patients effectively, ensure that data collection systems are robust, user-friendly and adaptable, plan adequate remote and on-site monitoring, maximize patient retention through continuous engagement with study sites and ensure that everyone involved in the study forms a friendly and effective team. Observational studies such as DISCOVER are crucial for understanding disease epidemiology and management in real-world settings. They are also increasingly used by governmental, regulatory and payor agencies for post-marketing surveillance and when considering new drug submissions. The development of future studies of similar scope and ambition to DISCOVER is encouraged.

Benralizumab Prevents Recurrent Exacerbations in Patients with Chronic Obstructive Pulmonary Disease: A Post Hoc Analysis.

Exacerbations in chronic obstructive pulmonary disease (COPD), which tend to occur in clusters and increase with disease severity, come with high societal and economic burdens. Prevention and delay of recurrent exacerbations is an unmet and significant therapeutic need for patients with COPD. GALATHEA (NCT02138916) and TERRANOVA (NCT02155660) were trials assessing efficacy of benralizumab in patients with frequent COPD exacerbations despite treatment. Although these studies found that benralizumab given as an add-on treatment did not significantly reduce annual rates of COPD exacerbations after 56 weeks of treatment, in the following exploratory post hoc analysis of the GALATHEA and TERRANOVA trials we identified a potential responder population in which treatment with benralizumab prevents recurrent COPD exacerbations during 30- and 90-day periods following an initial exacerbation, a vulnerable period for an exacerbation to occur. This responder population was characterized by high blood eosinophil counts and frequent previous exacerbations despite optimized triple therapy. These results highlight the importance of targeted therapies for high-risk populations and merit further research into the benefits of biologic therapies for COPD exacerbations.

Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta.

Pamidronate (PAM) infusion is the standard treatment in children with osteogenesis imperfecta (OI). Zoledronic acid (ZOL) is a bisphosphonate with higher potency and faster intravenous infusion, but its efficacy and safety has not been established for OI patients. We report an open-label, prospective, and randomized clinical analysis to study the safety and efficacy of ZOL compared with PAM in 23 children with OI. They were selected to receive PAM (PAM group), 1 mg/kg/day, over 2 days or ZOL (ZOL group), 0.025-0.05 mg/kg/day, over 2 days every 3-4 months according to their ages, during a 1-year follow-up. They were observed for clinical and biochemical parameters, side effects, bone mineral density (BMD), and fracture rate. After treatment, the PAM and ZOL groups average lumbar spine (LS) BMD increased by 51.8% (p = 0.053) and 67.6% (p = 0.003), respectively. Parallel improvement was seen in LS Z-score in the PAM and ZOL groups, with scores of -5.3 to -3.8 (p = 0.032) and -4.8 to -2.3 (p = 0.007), respectively. LS Z-score for the ZOL group at the end of treatment was higher compared with the PAM group but only a borderline significance (p = 0.053). The total alkaline phosphatase (AP) in the ZOL group significantly decreased from baseline at third and fourth infusion (p = 0.032). Mild side effects were similar in both groups, but no severe clinical symptoms were reported. In conclusion, the present study shows that the use of ZOL in the dosage and period studied was safe and efficient to promote a clinical and densitometric improvement, similarly to PAM. Further studies are needed to establish optimal dosing and long-term safety.

Socioeconomic Factors Associated With Glycemic Measurement and Poor HbA1c Control in People With Type 2 Diabetes: The Global DISCOVER Study.

DISCOVER is a 3-year observational study program of 15,983 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. We investigated the association between socioeconomic status and both the availability of a baseline glycated hemoglobin (HbA1c) measurement and poor glycemic control (HbA1c level ≥ 9.0%) in participants enrolled in DISCOVER. Factors associated with a lack of baseline HbA1c measurement or an HbA1c level ≥ 9.0% were assessed using three-level hierarchical logistic models. Overall, 19.1% of participants did not have a baseline HbA1c measurement recorded. Lower-middle country income (vs. high) and primary/no formal education (vs. university education) were independently associated with a reduced likelihood of having a baseline HbA1c measurement (odds ratio [95% confidence interval]: 0.11 [0.03-0.49] and 0.81 [0.66-0.98], respectively. Of the participants with an available HbA1c measurement, 26.9% had an HbA1c level ≥ 9.0%; 68.7% of these individuals were from lower- or upper-middle-income countries. Factors associated with an increased likelihood of poor glycemic control included low country income, treatment at a site with public and/or governmental funding (vs. private funding) and having public or no health insurance (vs. private). A substantial proportion of DISCOVER participants did not have an HbA1c measurement; more than one-quarter of these participants had poorly controlled type 2 diabetes. Both individual- and country-level socioeconomic factors are associated with the quality of care regarding glycemic control. Awareness of these factors could help improve the management of patients with type 2 diabetes.

Early versus late intensification of glucose-lowering therapy in patients with type 2 diabetes: Results from the DISCOVER study.

AIMS: To assess the effects of glycated haemoglobin (HbA1c) levels at time of glucose-lowering treatment intensification in DISCOVER, a global observational study of patients with type 2 diabetes (T2D) initiating second-line therapy. Outcomes of interest were glycaemic control, hypoglycaemia, and need for further intensification during 3 years of follow-up. METHODS: We included patients who intensified treatment (add-on or insulin initiation) upon initiation of second-line therapy (baseline). Outcomes were assessed according to baseline HbA1c: HbA1c ≤ 7·5% (early intensification) or HbA1c > 7·5% (late intensification). Factors associated with early or late intensification were assessed using multivariate logistic regression. RESULTS: Of the 9575 patients included, 3275 (34·2%) intensified treatment early and 6300 (65·8%) intensified treatment late. During follow-up, mean (SD) HbA1c was lower in the early- than in the late-intensification group (6·9% [0·95%] vs 7·5% [1·28%] at 36 months). More patients had HbA1c < 7·0% in the early- than in the late-intensification group (61·8% vs 37·9% at 36 months; p < 0·001). The risk of further intensification was higher in the late-intensification group (hazard ratio 1·88 [95% confidence interval 1·68-2·09]). Occurrence of hypoglycaemia was similar in both groups. CONCLUSIONS: Late intensification of glucose-lowering therapy after first-line treatment failure reduces the likelihood of reaching recommended treatment goals.

Contemporary economic burden in a real-world heart failure population with Commercial and Medicare supplemental plans.

BACKGROUND: Limited real-world data exist on healthcare resource utilization (HCRU) and associated costs of patients with heart failure (HF) with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), including urgent HF visits, which are assumed to be less burdensome than HF hospitalizations (hHFs) HYPOTHESIS: This study aimed to quantify the economic burden of HFrEF and HFpEF, via a retrospective, longitudinal cohort study, using IBM® linked claims/electronic health records (Commercial and Medicare Supplemental data only). METHODS: Adult patients, indexed on HF diagnosis (ICD-10-CM: I50.x) from July 2012 through June 2018, with 6-month minimum baseline period and varying follow-up, were classified as HFrEF (I50.2x) or HFpEF (I50.3x) according to last-observed EF-specific diagnosis. HCRU/costs were assessed during follow-up. RESULTS: About 109 721 HF patients (22% HFrEF, 31% HFpEF, 47% unclassified EF; median 18 months' follow-up) were identified. There were 3.2 all-cause outpatient visits per patient-month (HFrEF, 3.3; HFpEF, 3.6); 69% of patients required inpatient stays (HFrEF, 80%; HFpEF, 78%). Overall, 11% of patients experienced hHFs (HFrEF, 23%; HFpEF, 16%), 9% experienced urgent HF visits (HFrEF, 15%; HFpEF, 12%); 26% were hospitalized less than 30 days after first urgent HF visit versus 11% after first hHF. Mean monthly total direct healthcare cost per patient was $9290 (HFrEF, $11 053; HFpEF, $7482). CONCLUSIONS: HF-related HCRU is substantial among contemporary real-world HF patients in US Commercial or Medicare supplemental health plans. Patients managed in urgent HF settings were over twice as likely to be hospitalized within 30 days versus those initially hospitalized, suggesting urgent HF visits are important clinical events and quality improvement targets.

Type 2 diabetes and heart failure: insights from the global DISCOVER study.

AIMS: Heart failure (HF) is increasingly recognized as a major cause of morbidity and mortality in patients with type 2 diabetes (T2D), but the global epidemiology and treatment of HF in T2D are not well defined. This study aimed to examine the global prevalence of HF and the incidence of HF over 3 years of follow-up in patients with T2D [by presence and absence of co-existing coronary artery disease (CAD)]. METHODS AND RESULTS: DISCOVER was a 3 year, prospective, observational study of T2D patients enrolled at initiation of second-line glucose-lowering therapy. Among 14 057 patients with T2D from 36 countries, 289 (2.1%) had a diagnosis of HF at enrolment; median prevalence across countries was 2.0% (inter-quartile range 1.0-3.1%). Patients with HF at baseline were more likely to be older [HF vs. no HF: 67 ± 12 vs. 57 ± 12 years, standardized difference (StDiff) = 84%] and have longer duration of T2D (8.1 ± 7.2 vs. 5.6 ± 5.2 years, StDiff = 40%), CAD (44% vs. 6%, StDiff = 97%), atrial fibrillation (21% vs. 1%, StDiff = 66%), and kidney disease (23% vs. 4%, StDiff = 55%). Patients with HF were less likely to be on metformin (66% vs. 79%, StDiff = 28%) and thiazolidinediones (5.5% vs. 10.6%, StDiff = 19%) but had similar use of other glucose-lowering medications. Among 9313 patients with follow-up data, there were 70 incident cases of HF, which translates to an incidence of 2.6 cases per 1000 person years. Of these incident HF cases, 60% occurred in the absence of pre-existing or concomitant CAD, and 73% were diagnosed in the outpatient setting. CONCLUSIONS: In a large, global cohort of patients with T2D, the majority of incident cases of HF occurred in outpatients and in the absence of known CAD. These findings highlight the need for greater awareness of HF risk in patients with T2D.

Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin.

OBJECTIVE: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. MATERIALS AND METHODS: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms. RESULTS: Dapagliflozin showed significantly greater mean reductions versus saxagliptin in HbA1c (difference versus saxagliptin [95% CI]: -0.32% [-0.54, -0.10]; p < 0.005), fasting plasma glucose (-0.98 [-1.42, -0.54] mmol/L; p < 0.0001), body weight (-2.39 [-3.08, -1.71] kg; p < 0.0001) and systolic blood pressure (SBP) (-3.89 [-6.15, -1.63] mmHg; p < 0.001). More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0.5%, weight loss ≥ 2 kg, SBP reduction ≥ 2 mmHg and no major/minor hypoglycemia (24% versus 7%). No major events of hypoglycemia were reported. More patients on dapagliflozin (6%) versus saxagliptin (0.6%) experienced genital infections. CONCLUSION: Dapagliflozin demonstrated greater glycemic efficacy than saxagliptin with additional benefits on weight and SBP, and the safety profile was consistent with previous studies.

[Prevalence of vitamin D deficiency, insufficiency and secondary hyperparathyroidism in the elderly inpatients and living in the community of the city of São Paulo, Brazil]. / Prevalência da deficiência, insuficiência de vitamina D e hiperparatiroidismo secundário em idosos institucionalizados e moradores na comunidade da cidade de São Paulo, Brasil.

The occurrence of osteoporotic fractures in the elderly is associated with reduced levels of vitamin D and resulting secondary hyperparathyroidism, and inpatients are the ones at a higher risk. In Brazil, given its high level of insolation, the populations large amount of vitamin D is inferred to be adequate. In this study we aimed to assess the serum levels of 25-hydroxivitamin D (25OHD), parathormone (PTH) and ionized calcium (Cai), as well as to analyze the prevalence of both hypovitaminosis D and secondary hyperparathyroidism in the elderly living in the city of São Paulo. We studied 177 inpatients (125 women and 52 men) with mean age (SD) 76.6 (9.0) years, and 243 outpatients (168 women and 75 men) aged 79.1 (5.9) years. In this assessment 71.2% in the inpatients group and 43.8% in the outpatients group had 25OHD levels below the minimum recommended (50 nmol/l), with the women presenting with levels considerably lower than the men. Secondary hyperparathyroidism occurred in 61.7% of the inpatients and in 54% of the outpatients. Considering the results achieved, we recommend vitamin D supplementation in effective doses for the Brazilian elderly population, in addition to suggesting a discussion for the implementation of vitamin D-enhanced food policies, particularly oriented to the ones at a greater risk.

Dapagliflozin versus saxagliptin as add-on therapy in patients with type 2 diabetes inadequately controlled with metformin

ABSTRACT Objective: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. Materials and methods: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms. Results: Dapagliflozin showed significantly greater mean reductions versus saxagliptin in HbA1c (difference versus saxagliptin [95% CI]: −0.32% [-0.54, −0.10]; p < 0.005), fasting plasma glucose (-0.98 [-1.42, −0.54] mmol/L; p < 0.0001), body weight (-2.39 [-3.08, −1.71] kg; p < 0.0001) and systolic blood pressure (SBP) (-3.89 [-6.15, −1.63] mmHg; p < 0.001). More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0.5%, weight loss ≥ 2 kg, SBP reduction ≥ 2 mmHg and no major/minor hypoglycemia (24% versus 7%). No major events of hypoglycemia were reported. More patients on dapagliflozin (6%) versus saxagliptin (0.6%) experienced genital infections. Conclusion: Dapagliflozin demonstrated greater glycemic efficacy than saxagliptin with additional benefits on weight and SBP, and the safety profile was consistent with previous studies.

Seasonal variation in the serum 25-hydroxyvitamin D levels of young and elderly active and inactive adults in São Paulo, Brazil: The São PAulo Vitamin D Evaluation Study (SPADES).

OBJECTIVE: To evaluate the 25-hydroxyvitamin D [25(OH)D] concentrations in individuals in the city of São Paulo belonging to different age groups and exhibiting specific behavioral characteristics and to correlate the 25(OH)D concentration with the level of UV radiation (UVR). PATIENTS AND METHODS: A total of 591 individuals were included, distributed as follows: 177 were living in institutions (NURSING, 76.2 ± 9.0 y old), 243 were part of the community elderly (COMMUNITY, 79.6 ± 5.3 y old), 99 were enrolled in a physical activity program targeting the elderly (ACTIVE, 67.6 ± 5.4 y old) and 72 were young (YOUNG, 23.9 ± 2.8 y old). Blood samples from all individuals were collected throughout the year. UVR measurements were taken by an official meteorology institution. RESULTS: The UVR values varied throughout the year, following a sinusoidal-like pattern. Because of the Earth's orbit, we hypothesized that there would be cyclic patterns for the 25(OH)D and UVR values that repeat every 12 mo. The general formula is represented by the equation P1+P2⋅sin(-2⋅π12⋅(t-P3)) The mean 25(OH)D concentration and the amplitude of the variation were significantly higher for the YOUNG and ACTIVE groups than for the COMMUNITY and NURSING groups. The nadir for UVR was in June, whereas the nadir for the 25(OH)D concentration was in the spring, corresponding to a delay of one season. CONCLUSIONS: There was seasonal variation in the 25(OH)D concentration for all the groups studied; however, the amplitude of the variation was higher for the groups of young and physically active people, possibly due to the higher level of sunlight exposure for these groups. The lowest 25(OH)D concentration was detected in the spring.

Diabetes mellitus no Brasil: características clínicas, padrão de tratamento e custos associados ao cuidado da doença / Diabetes Mellitus in Brazil: clinical characteristics, standard treatment choice and cost

Objetivo: Descrever a utilização de recursos de saúde associados ao tratamento do Diabetes Mellitus tipo 2 (DM2) no sistema público de saúde brasileiro, assim como o padrão de tratamento e seus eventos adversos, a ocorrência de complicações vasculares e o controle metabólico nos pacientes. Métodos: Estudo observacional, retrospectivo, conduzido em 4 centros do Sistema Único de Saúde envolvendo pacientes com DM2. Os dados foram coletados dos prontuários médicos de setembro a dezembro de 2013. Foi conduzida análise descritiva considerando três faixas de duração da doença desde o seu diagnóstico e a estratificação dos pacientes de acordo com o período recordatório e presença de complicações vasculares. Resultados: 161 pacientes foram analisados. Os principais esquemas terapêuticos utilizados foram a combinação de metformina, insulina NPH e insulina regular; de glibenclamida e metformina; e metformina isolada. A associação metformina e insulina apresentou maior frequência de eventos adversos (28,9%) e a glibenclamida, metformina e insulina, menor frequência (5,7%). A maioria dos pacientes mostrou complicações microvasculares, sendo nefropatia e neuropatia frequentes em todos os estratos analisados. Em pacientes com DM2 avançado (≥ 15 anos de duração), a retinopatia mostrou-se prevalente. A frequência de eventos macrovasculares variou de 21,3% a 37,9% entre os grupos, sendo a doença coronariana a mais frequente. Um custo total médio de R$ 931,88±1.400,75 por paciente foi observado para os pacientes sem complicações vasculares e de R$ 1.212,37±1.012,38 para aqueles com complicações. Conclusão: Informações relevantes sobre o manejo de pacientes brasileiros com DM2 foram descritas, sugerindo alta frequência de complicações vasculares e maiores custos associados a elas.

Objective: The aim of this study is to describe the use of public health resources to Type 2 Diabetes Mellitus (T2DM) and its costs in Brazil. Furthermore, we describe the standard treatment choice and its related adverse events as well as patients' metabolic control and vascular complications. Methods: This observational and retrospective study was conducted in four public health centers from Brazilian Public Health System (SUS); a secondary assistance level for long-term treatment for outpatients with T2DM. Data were collected from medical records from September to December 2013. A descriptive analysis is available for three groups according to time of disease since diagnosis. The recall and vascular complications were also considered. Results: 161 patients were studied. The most frequent treatments were metformin in monotherapy, metformin + NPH insulin + regular insulin and metformin + glibenclamide. Metformin + insulin therapy had the highest rate of adverse events (28.9%), while glibenclamide + metformin + insulin therapy, the lowest rate (5.7%). The majority of patients developed microvascular complications, specially nephropathy and neuropathy. Retinopathy was the most frequent complication for the group of patients with end stage T2DM (≥ 15 years). The frequency of macrovascular events ranged from 21.3% to 37.9% between groups. Coronary disease was the most frequent macrovascular complications. The mean cost per patient was R$ 1.212,37±1.012,38 for patient group presenting vascular complications and R$ 931,88±1.400,75 for the group not presenting complications. Conclusion: We describe current use of public health resources regarding T2DM treatment in Brazil, as well as T2DM treatment´s characteristics.

Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus.

OBJECTIVE: To compare the aerobic exercise capacity between normal adolescents and those with type 1 diabetes mellitus (T1DM). METHODS: An experimental group with 72 individuals diagnosed with T1DM aged 9--20, time from diagnosis 4.9 +/- 3.6 yr, without clinical cardiopulmonary disease or anemia and a control group (C) with 46 healthy individuals aged 10--18, matched by age, weight, height, body mass index, and lean and fat mass (kg), underwent an incremental aerobic exercising test on a motorized treadmill, where gas exchange variables - peak pulmonary ventilation (VE), peak oxygen consumption (VO(2)), and carbon dioxide production (CO(2)) - as well as their heart rate (HR) and time to exhaustion were recorded. RESULTS: Body mass composition had no significant difference between experimental and control groups, and male and female subjects had similar exercising performances. The mean of hemoglobin A1c in the control group was 5.2+/- 0.9% and in the diabetic group 8.1+/- 2.2%; p=0.000. The patients with T1DM showed lower levels of aerobic capacity than the control group. Their respective values for each variable were as follows: (i) maximal VO(2) (T1DM: 41.57+/-7.68 vs. C: 51.12+/- 9.94 mL/kg/min; p< 0.001) and (ii) maximal VE (T1DM: 76.39+/-19.93 vs. C: 96.90 +/- 25.72 mL/kg/min; p< 0.001). Patients with T1DM also had an earlier time to exhaustion (T1DM: 8.75+/-1.60 vs. 10.82+/-1.44 min). CONCLUSIONS: Adolescent patients with T1DM showed a reduced aerobic exercising capacity when compared to healthy peers matched to anthropometric conditions. This potential condition should be taken into consideration by the time of evaluation of the aerobic performance of these patients with glycemic control level.

Influence of ultraviolet radiation on the production of 25 hydroxyvitamin D in the elderly population in the city of São Paulo (23 degrees 34'S), Brazil.

The lack of vitamin D is a major changeable factor involved in the pathophysiology of osteoporosis. Since the major source for this hormone is its cutaneous synthesis via ultraviolet radiation (UVR), we studied the serum level of 25-hydroxyvitamin D (25OHD) in 250 free-living elderly people (79.1 years old) from a subtropical region according to the UVR incidence and its correlations with parathormone (PTH) and ionized calcium. UVR and 25OHD differed according to the season of the year (P<0.001), with greater radiation in the summer and less in the winter, whereas the 25OHD peak and nadir occurred in autumn and spring, respectively. The highest 25OHD mean was 67.2 nmol/l, and the lowest was 29.1 nmol/l corresponding, respectively, to the measure of the month subsequent to the one of most and least sunlight incidence. Clustered by season, the correlation between UVR and 25OHD for the following seasons was r=0.98 and between the PTH and 25OHD of corresponding seasons, r=-0.95. Vitamin D deficiency occurred in 15.4% of patients, insufficiency in 41.9% and secondary hyperparathyroidism in 55%. In conclusion, we found a seasonal variation in 25OHD levels that strongly correlated with the PTH levels when separated by the seasons of the year. The 25OHD levels correlated with the UVR of the previous quarter, requiring no less than 30 days for serum changes arising from exposure to or deprivation of UVR to be observed. The prevalence of vitamin D deficiency/insufficiency found was greater than expected, even when compared to countries exposed to less solar irradiation. Thus, measures to encourage greater sun exposure and food enrichment policies should also be considered.

Bone mineral density and osteoporosis among a predominantly Caucasian elderly population in the city of São Paulo, Brazil.

This cross-sectional study covered 301 individuals over 70 years of age--207 women (W) and 94 men (M)--living in the city of São Paulo, Brazil. Our aims were to evaluate the prevalence of low bone mineral density (BMD) in this population and the possible factors that influence BMD. The subjects were submitted to a bone densitometry scan (DXA) to evaluate the BMD at lumbar spine (LS), femoral neck (FN), trochanter (T), total femur (TF) and total body composition. At the time, the participants filled in a questionnaire about lifestyle habits, diet and medical history, as well as having blood samples taken to check hormone and biochemical levels. Anthropometric parameters were measured. Osteopenia and osteoporosis were defined in accordance with the criteria suggested by the World Health Organization. In the different sites studied, the prevalence of osteopenia and osteoporosis varied, in men ranging 33.3-57.4% and 6.4-16.1%, respectively, and in women ranging 36.6-56.5% and 22.2-33.2%, respectively. Weight was the variable that most strongly correlated with BMD at the proximal femur in both sexes (men, r =0.44-0.52; women, r =0.48-0.52) and with BMD at LS in women (r =0.44). Height was the parameter that best correlated with BMD at LS in men (r =0.34). In men follicle-stimulating hormone, growth hormone and glycemia correlated with BMD at T and TF, while plasma albumin only correlated with BMD at T. In women glycemia correlated with BMD at LS, and follicle-stimulating hormone correlated with BMD at FN, T and TF. In conclusion, we found a high prevalence of osteopenia and osteoporosis in this population, with weight being the best predictor of BMD. The prevalence of osteoporosis and osteopenia at FN was as high in men as that observed in women.