Antonio Roberto Chacra

Effect of valsartan on the incidence of diabetes and cardiovascular events

BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)

Effect of nateglinide on the incidence of diabetes and cardiovascular events

BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial.

Aims:  Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy.

Alterações metabólicas da síndrome lipodistrófica do HIV

A introducao da highly active antiretroviral therapy (HAART) - terapia anti-retroviral fortemente ativa - vem reduzindo a morbidade e a mortalidade em pacientes infectados com o virus da imunodeficiencia humana (HIV). Entretanto, tratamentos prolongados, com combinacoes de drogas, sao de dificil manutencao devido a ma aderencia e aos efeitos toxicos. O tratamento com agentes anti-retrovirais, especialmente os inibidores da protease, fez surgir uma sindrome caracterizada por redistribuicao anormal da gordura corporal, alteracoes no metabolismo glicemico, resistencia insulinica e dislipidemia, chamada de sindrome lipodistrofica do HIV (SLHIV). Atualmente nao existe nenhum consenso para prevencao ou tratamento da sindrome, cuja causa permanece desconhecida. Esta revisao enfatiza os achados clinicos e dados da literatura a respeito da SLHIV, pois um melhor entendimento desta sindrome por infectologistas, cardiologistas e endocrinologistas e essencial para o manejo da doenca.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents--protease inhibitors in particular--has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.The introduction of highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with the human immunodeficiency virus (HIV). However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. Treatment with antiretroviral agents - protease inhibitors in particular - has uncovered a syndrome of abnormal fat redistribution, impaired glucose metabolism, insulin resistance and dyslipidemia, collectively termed lipodystrophy syndrome (SLHIV). Nowadays, no clinical guidelines are available for the prevention or treatment of SLHIV, and its cause have yet to be totally elucidated. This review emphasizes the clinical features and the data from previous studies about the SLHIV taking into account that a better understanding of this syndrome for HIV specialists, cardiologists and endocrinologists is fundamental for the disease control.

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).

Safety and efficacy of saxagliptin in combination with submaximal sulphonylurea versus up-titrated sulphonylurea over 76 weeks

To assess the long-term efficacy and safety of saxagliptin in patients with type 2 diabetes mellitus inadequately controlled on sulphonylurea monotherapy, 768 patients were randomised to saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg versus placebo added to up-titrated glyburide over 76 weeks (24 weeks plus 52-week extension) in this phase 3, double-blind, placebo-controlled trial; 557 patients completed the study, 142 without being rescued. At 76 weeks, adjusted mean changes from baseline HbA1C (repeated measures model) (95% confidence interval) for saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide were 0.11% (-0.05, 0.27), 0.03% (-0.14, 0.19), and 0.69% (0.47, 0.92), respectively (post hoc and nominal p < 0.0001 for saxagliptin 2.5 and 5 mg vs. up-titrated glyburide). Adverse event frequency was similar in all treatment groups; reported hypoglycaemia event rates were 24.2%, 22.9%, and 20.6% with saxagliptin 2.5 mg, saxagliptin 5 mg, and up-titrated glyburide, respectively. Saxagliptin plus glyburide provided sustained incremental efficacy compared with up-titrated glyburide over 76 weeks, and was generally well tolerated.

Efficacy and safety of saxagliptin in older patients with type 2 diabetes mellitus

Abstract Objective: To assess the safety and efficacy of saxagliptin (5 mg once-daily) in older patients (≥65 years of age) with inadequately controlled type 2 diabetes. Research design and methods: In this retrospective subgroup analysis, data from five randomized, double-blind, placebo-controlled, multicenter, 24-week, phase 3 trials were included. The primary studies evaluated saxagliptin 5 mg once-daily (monotherapy or add-on) in patients aged 18–77 years with HbA1c ≥7.0% (four studies) or ≥7.5% (add-on to glyburide study) versus placebo. Main outcome measures: The primary efficacy endpoint of each study included in this pooled analysis was HbA1c change from baseline to week 24. Results: In the five-study pooled population, 279 (16.6%) patients were at least 65 years old; 142 received saxagliptin 5 mg once-daily and 137 received placebo. Treatment groups were well-balanced for baseline characteristics within each study. In older patients, the HbA1c adjusted mean change from a baseline of 8.1% was −0.73 ± 0.16% (mean ± SEM) with saxagliptin compared with −0.17 ± 0.14% for placebo from a baseline of 8.0%. Adverse event rates were similar with saxagliptin 5 mg once-daily compared with placebo in older patients. Conclusion: The pooled subgroup analysis of saxagliptin 5 mg once-daily monotherapy and add-on therapy trials demonstrated clinically relevant and significant efficacy for reducing HbA1c in older (≥65 years) patients. Saxagliptin was well-tolerated in older patients with a low incidence of hypoglycemia and no weight gain.

Neuropatia autonômica cardiovascular diabética: fatores de risco, impacto clínico e diagnóstico precoce

Cardiovascular autonomic neuropathy (CAN) is one of the most clinically significant complications of diabetes mellitus (DM), but one of the least frequently diagnosed. In this review, we discuss the major risk factors for the development and progression of CAN in patients with DM, the natural history of autonomic neuropathy and its impact on cardiovascular disease in DM, as well as the tests for the early diagnosis and staging of CAN in the clinical practice. The bibliographic research was based on two databases: Medline and Tripdatabase, with the following descriptors: diabetic cardiovascular autonomic neuropathy and cardiovascular autonomic neuropathy and diabetes. We selected English and German articles, written between 1998 and 2007. In its initial stages (early and intermediate), CAN may be diagnosed and reversed. However, in advanced cases (severe stage), the only treatment that remains is a symptomatic one. CAN is associated with higher cardiovascular morbidity and mortality rates and poor quality of life in diabetic individuals.

Low cardiorespiratory fitness in people at risk for type 2 diabetes: early marker for insulin resistance

PurposeThere is a significant association between insulin resistance and low cardiorespiratory fitness in nondiabetic subjects. In a population with risk factors for type 2 diabetes (T2DM), before they are insulin resistant, we investigated low exercise capacity (VO2max) as an early marker of impaired insulin sensitivity in order to determine earlier interventions to prevent development of insulin resistance syndrome (IRS) and T2DM.MethodsCross-sectional analyses of data on 369 (78 men and 291 women) people at risk for IRS and T2DM, aged 45.6 +/- 10 years (20-65 years) old from the Community Diabetes Prevention Project in Minnesota were carried out. The cardiorespiratory fitness (VO2max) by respiratory gas exchange and bicycle ergometer were measured in our at risk non insulin resistant population and compared with a control group living in the same geographic area. Both groups were equally sedentary, matched for age, gender and BMI.ResultsThe most prevalent abnormality in the study population was markedly low VO2max when compared with general work site screening control group, (n = 177; 137F; 40 M, mean age 40 ± 11 years; BMI = 27.8 ± 6.1 kg/m2). Individuals at risk for IRS and T2DM had a VO2max (22 ± 6 ml/kg/min) 15% lower than the control group VO2max (26 ± 9 ml/kg/min) (p < 0.001). It was foun that VO2max was inversely correlated with HOMA-IR (r = -0.30, p < 0.0001).ConclusionsDecreased VO2max is correlated with impaired insulin sensitivity and was the most prevalent abnormality in a population at risk for IRS and T2DM but without overt disease. This raises the possibility that decreased VO2 max is among the earliest indicators of IRS and T2DM therefore, an important risk factor for disease progression.

Internações por pé diabético: comparação entre o custo direto estimado e o desembolso do SUS

This study aimed to analyze costs for treating patients with diabetic foot cared by the public Brazilian Health System (SUS), comparing the estimated cost with the amount of SUS reimbursement. A cohort prospective study carried out in hospitals that provide services for the Unified Health System in Sergipe, involving 109 hospitalization episodes of patients with diabetes and foot ulcers. We follow these patients day by day and estimated the hospital direct cost and the SUS reimbursement. All patients had type 2 diabetes and the majority of ulcers (64,2%) were classified as Wagner 4 or 5. Forty-three (39,4%) healed without amputation and fifty-two (47,7%) healed with amputation. Fourteen (12,8%) patients died. Hospital direct cost ranged from R