RESUMEN
OBJECTIVE: In the ACCORD trial, intensive treatment of patients with type 2 diabetes and high cardiovascular (CV) risk was associated with higher all-cause and CV mortality. Post hoc analyses have failed to implicate rapid reduction of glucose, hypoglycemia, or specific drugs as the causes of this finding. We hypothesized that exposure to injected insulin was quantitatively associated with increased CV mortality. RESEARCH DESIGN AND METHODS: We examined insulin exposure data from 10,163 participants with a mean follow-up of 5 years. Using Cox proportional hazards models, we explored associations between CV mortality and total, basal, and prandial insulin dose over time, adjusting for both baseline and on-treatment covariates including randomized intervention assignment. RESULTS: More participants allocated to intensive treatment (79%) than standard treatment (62%) were ever prescribed insulin in ACCORD, with a higher mean updated total daily dose (0.41 vs. 0.30 units/kg) (P < 0.001). Before adjustment for covariates, higher insulin dose was associated with increased risk of CV death (hazard ratios [HRs] per 1 unit/kg/day 1.83 [1.45, 2.31], 2.29 [1.62, 3.23], and 3.36 [2.00, 5.66] for total, basal, and prandial insulin, respectively). However, after adjustment for baseline covariates, no significant association of insulin dose with CV death remained. Moreover, further adjustment for severe hypoglycemia, weight change, attained A1C, and randomized treatment assignment did not materially alter this observation. CONCLUSIONS: These analyses provide no support for the hypothesis that insulin dose contributed to CV mortality in ACCORD.
Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
OBJECTIVES: To describe changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) associated with initiation and continued use of combined oral contraceptives (COCs) in healthy adolescents. STUDY DESIGN: This observational, matched cohort study was conducted in 2 large health systems. Utilizing claims and electronic medical records, we identified adolescents 14-17.9 years of age initiating medium-dose COCs (containing 30 or 35 (µg of ethinyl estradiol or equivalent and a progestin) between July 1, 2007 and December 31, 2009 with a baseline and at least 1 follow-up blood pressure (BP) and BMI. COC-users were matched 1:2 by age, race/ethnicity, and site to controls (COC-nonusers). All BPs and BMIs recorded during outpatient visits starting 1 month prior to COC initiation (index date for controls), through December 31, 2010 were collected. Mixed model linear regression with random intercepts and slopes were then used to estimate changes in SBP, DBP, and BMI over time. RESULTS: The 510 adolescent COC-users and 912 controls did not differ significantly by age, race/ethnicity, insurance, and baseline SBP, DBP, or BMI. After adjusting for baseline values, over a median of 18 months follow-up, COC-users had an decrease in SBP of 0.07 mm Hg/mo, and controls had an increase of 0.02 mm Hg/mo (P = .65). Similarly, DBP decreased by 0.007 mm Hg/mo in COC-users vs 0.006 mm Hg/mo in controls (P = .99). BMI increased by 0.04 (kg/m(2))/mo in COC-users vs 0.025 (kg/m(2))/mo in controls (P = .09). CONCLUSIONS: These data should provide reassurance to patients and providers regarding the lack of significant associations between COC-use and BMI or BP changes in adolescents.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Índice de Masa Corporal , Anticonceptivos Orales/administración & dosificación , Adolescente , Determinación de la Presión Sanguínea , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Minnesota , Análisis de RegresiónRESUMEN
OBJECTIVE: To examine changes in bone and body composition of adolescent female artistic gymnasts (GYM; n = 7), level 5+, compared with nongymnast controls (CON; n = 10) over 3 years. STUDY DESIGN: Areal bone mineral density (aBMD; g/cm(2)), bone mineral content (BMC; g) and bone area (cm(2)), of the total body (TB), total proximal femur (TPF), trochanter (Tr), femoral neck, lumbar spine (LS), and distal radius were measured using dual-energy X-ray absorptiometry. Fat-free soft tissue mass (FFST; g), fat mass (g), and percent body fat (%FAT) were also assessed. RESULTS: No initial differences in height or weight between GYM and CON were observed, and both groups demonstrated parallel increases in these parameters over time (P <.05; h(2) >or=0.15). At baseline, GYM possessed significantly lower %FAT and higher aBMD at all sites (except TB; P <.05; h(2) >or=0.15). Over 3 years, GYM increased more than CON (P <.05; eta (2) >or=0.15) in TB, Tr, and TPF aBMD, TB and LS BMC, and FFST. CONCLUSION: Female adolescents participating in competitive artistic gymnastics training over 3 years have enhanced rates of aBMD, BMC and FFST accrual.