Alina Coutinho Rodrigues Feitosa

Glycemia and cardiovascular disease in type 1 diabetes mellitus.

OBJECTIVE To evaluate the role of glycemic control in the development of cardiovascular disease (CVD) in type 1 diabetes mellitus (DM). METHODS We review the literature regarding coronary atherosclerosis, coronary artery calcification, and the epidemiologic studies related to the role of glycemia and the classic risk factors for coronary artery disease (CAD) in type 1 DM. RESULTS Four prospective studies (Wisconsin Epidemiologic Study of Diabetic Retinopathy, EURODIAB, Steno Diabetes Center Study of Adults With Type 1 DM, and Pittsburgh Epidemiology of Diabetes Complications study) do not show that glycemic control predicts CAD occurrence. Findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study show that compared with conventional insulin therapy, intensive insulin therapy reduces CVD among patients with type 1 DM and is associated with lower prevalence of coronary artery calcification. The discrepancies between the findings from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study and the Pittsburgh Epidemiology of Diabetes Complication study are likely due to differences between the study populations and the lower prevalence of renal disease in the former study. Besides duration of DM and albuminuria/overt nephropathy, insulin resistance is a major determinant of CAD associated with type 1 DM. CONCLUSIONS Discrepant study results regarding the relationship between glycemia and CAD/coronary artery calcification may be related to the prevalence of renal disease and the presence of the metabolic syndrome. Published data suggest that addressing traditional risk factors including albuminuria, the metabolic syndrome, and inflammatory markers is better for preventing and treating CAD than focusing exclusively on glycemic control, which is still necessary for preventing microvascular complications. Furthermore, there is a synergistic effect of glycemic control and albuminuria on the development of CVD.

Doença cardiovascular no diabetes melito tipo 1

The association between type 1 diabetes and coronary heart disease has become very clear since the late 1970. It has been demonstrated that there is an important increased risk in morbidity and mortality caused by coronary artery disease in young adults with type 1 diabetes compared with the non diabetic population. The underlying pathogeneses is still poorly understood. While the role of glycemic control in the development of microvascular disease complication is well established its role in CVD in patients with DM1 remains unclear with epidemiologic studies reporting conflicting data. Recent findings from the DCCT/EDIC showed that prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced level of HbA1c during the DCCT. The improvement of glycemic control itself appeared to be particularly effective in younger patients with shorter duration of the disease. Other analyses suggested the glycemia may have a stronger effect on CAD in patients without than in those with albuminúria. Other major determinants of coronary artery disease are the components of metabolic syndrome and the surrogate measure of insulin resistence: eGDR. It is proposed that patients with DM1 should have aggressive medical therapy, risk factor modification and careful monitoring not only of his blood sugar but also of the other processes involved in the atherosclerotic process, mostly the ones with family history of type 2 diabetes.

Transferência de lípides para a lipoproteína de alta densidade (HDl) em mulheres com diabetes melito tipo 1

INTRODUCTION People with type 1 diabetes mellitus (T1DM) have an increased risk of cardiovascular disease and may still have a normal lipid profile. In order to clarify whether normal HDL cholesterol levels may conceal defects in HDL function, we have studied the transfer of lipids to HDL in T1DM. METHODS Twenty-one young women with T1DM were compared with 21 non-diabetic women. Nanoemulsion preparations were used as lipid donor to HDL: one labeled with (3)H-triglycerides and 14C-free cholesterol and the other with (3)H-cholesteryl esters and 14C-phospholipids. These preparations were incubated with plasma samples for 1h. After chemical precipitation, the supernatant containing HDL was counted for radioactivity. RESULTS No difference in transfer was observed to nanoemulsion HDL from cholesteryl esters, triglycerides, free cholesterol and phospholipids. CONCLUSION Simultaneous lipid transfer to HDL was not affected in T1DM patients. This suggests that the disease does not alter lipoprotein composition and transfer protein action in such way as to disturb HDL metabolism.

Lipid transfer to HDL in type-2 diabetic patients: associations with microalbuminuria, statin, and insulin

FUNDAMENTO: La diabetes mellitus tipo 2 (DM2) es un factor de riesgo aislado para coronariopatia, principalmente cuando asociado a la microalbuminuria (MA). Alteraciones estructurales y funcionales de las lipoproteinas no estan totalmente aclaradas en ese contexto. OBJETIVO: Evaluar no solo la transferencia de lipidos hacia HDL (T) en pacientes DM2, sino tambien la asociacion tanto con la presencia de la MA como con el tratamiento con estatina o insulina. METODOS: Estudiamos a 33 pacientes con DM2 y 34 controles pareados para edad. Se incubo con plasma una nanoemulsion lipidica artificial radiomarcada con 3H-Triglicerido (TG) y 14C-colesterol libre (CL) o 3H-colesterol esterificado (CE) y 14C-fosfolipido (FL). Se procedio a la precipitacion de la nanoemulsion y de las lipoproteinas, con excepcion de la HDL, que tuvo su radioactividad contada. RESULTADOS: El valor de TFL (%) resulto mayor en el grupo con DM2 en confrontacion con el grupo-control (25,2±3,2 y 19,7±3,2 respectivamente; p < 0,001); la TCL (%), por su vez, obtuvo los siguientes resultados: 9,1±2,7 y 6,3±1,5 respectivamente; p < 0,001. El diagnostico de MA no se asocio a cambios de la propiedad de transferencia. El uso de la insulina se asocio al menor valor de TFL (%): 23,5±2,1 vs 26,1±3,3; p = 0,018. Ya el uso de la estatina se asocio a la baja del valor de todas las lipoproteinas - TCE (%): 3,5±0,9; TFL (%):23,8±2,0; TTG (%): 3,9±0,8; TCL (%):7,4±1,3 - si comparado al grupo que no usaba estatina (TCE (%):5,9±2,4; TFL (%):26,9±3,6; TTG (%):6,4±2,2; TCL (%):11,1±2,6). CONCLUSIONES: El DM2 aumento la transferencia de lipidos de superficie hacia HDL, mientras que el uso de estatina disminuyo todas las transferencias de lipidos. La presencia de MA no se asocio a las alteraciones de las transferencias de lipidos.BACKGROUND Type-2 diabetes mellitus (T2DM) is an isolated risk factor for coronary artery disease, especially when associated with microalbuminuria (MA). Structural and functional changes in lipoproteins have not yet been fully elucidated in this context. OBJECTIVE To assess lipid transfer (T) to HDL in type-2 diabetic patients and its association with microalbuminuria and treatment with statins or insulin. METHODS Thirty-three patients with type-2 diabetes mellitus and 34 age-matched control subjects were studied. A synthetic cholesterol-rich nanoemulsion radiolabeled with (3)H- triglycerides (TG) and 14C-free cholesterol (FC) or (3)H- cholesteryl ester (CE) and 14C-phospholipids (PL) was incubated with plasma. Both the nanoemulsion and lipoproteins were precipitated, except for HDL, which was counted for radioactivity. RESULTS PLT (%) was higher in the T2DM group than in the control group (25.2 +/- 3.2 and 19.7 +/- 3.2 respectively; p < 0.001), as was free cholesterol (% FC): 9.1 +/- 2.7 and 6.3 +/- 1.5 respectively; p < 0.001. The diagnosis of microalbuminuria (MA) was not associated with changes in lipid transfers. Insulin therapy was associated with lower PLT rates: 23.5 +/- 2.1 versus 26.1 +/- 3.3; p = 0.018. Statin therapy, in turn, was associated with a drop in all lipid transfers - CET 3.5 +/- 0.9; PLT: 23.8 +/- 2.0; TGT: 3.9 +/- 0.8; FCT: 7.4 +/- 1.3 - as compared to the group that was not on statin therapy (CET: 5.9 +/- 2.4; PLT: 26.9 +/- 3.6; TGT: 6.4 +/- 2.2; FCT: 11.1 +/- 2.6). CONCLUSION Type-2 diabetes mellitus increased lipid transfer to HDL particles, whereas statin therapy decreased all lipid transfers. The presence of MA was not associated with changes in lipid transfer.

Transferências lipídicas para HDL em diabéticos tipo 2: associações com microalbuminúria, estatina e insulina

FUNDAMENTO: La diabetes mellitus tipo 2 (DM2) es un factor de riesgo aislado para coronariopatia, principalmente cuando asociado a la microalbuminuria (MA). Alteraciones estructurales y funcionales de las lipoproteinas no estan totalmente aclaradas en ese contexto. OBJETIVO: Evaluar no solo la transferencia de lipidos hacia HDL (T) en pacientes DM2, sino tambien la asociacion tanto con la presencia de la MA como con el tratamiento con estatina o insulina. METODOS: Estudiamos a 33 pacientes con DM2 y 34 controles pareados para edad. Se incubo con plasma una nanoemulsion lipidica artificial radiomarcada con 3H-Triglicerido (TG) y 14C-colesterol libre (CL) o 3H-colesterol esterificado (CE) y 14C-fosfolipido (FL). Se procedio a la precipitacion de la nanoemulsion y de las lipoproteinas, con excepcion de la HDL, que tuvo su radioactividad contada. RESULTADOS: El valor de TFL (%) resulto mayor en el grupo con DM2 en confrontacion con el grupo-control (25,2±3,2 y 19,7±3,2 respectivamente; p < 0,001); la TCL (%), por su vez, obtuvo los siguientes resultados: 9,1±2,7 y 6,3±1,5 respectivamente; p < 0,001. El diagnostico de MA no se asocio a cambios de la propiedad de transferencia. El uso de la insulina se asocio al menor valor de TFL (%): 23,5±2,1 vs 26,1±3,3; p = 0,018. Ya el uso de la estatina se asocio a la baja del valor de todas las lipoproteinas - TCE (%): 3,5±0,9; TFL (%):23,8±2,0; TTG (%): 3,9±0,8; TCL (%):7,4±1,3 - si comparado al grupo que no usaba estatina (TCE (%):5,9±2,4; TFL (%):26,9±3,6; TTG (%):6,4±2,2; TCL (%):11,1±2,6). CONCLUSIONES: El DM2 aumento la transferencia de lipidos de superficie hacia HDL, mientras que el uso de estatina disminuyo todas las transferencias de lipidos. La presencia de MA no se asocio a las alteraciones de las transferencias de lipidos.BACKGROUND Type-2 diabetes mellitus (T2DM) is an isolated risk factor for coronary artery disease, especially when associated with microalbuminuria (MA). Structural and functional changes in lipoproteins have not yet been fully elucidated in this context. OBJECTIVE To assess lipid transfer (T) to HDL in type-2 diabetic patients and its association with microalbuminuria and treatment with statins or insulin. METHODS Thirty-three patients with type-2 diabetes mellitus and 34 age-matched control subjects were studied. A synthetic cholesterol-rich nanoemulsion radiolabeled with (3)H- triglycerides (TG) and 14C-free cholesterol (FC) or (3)H- cholesteryl ester (CE) and 14C-phospholipids (PL) was incubated with plasma. Both the nanoemulsion and lipoproteins were precipitated, except for HDL, which was counted for radioactivity. RESULTS PLT (%) was higher in the T2DM group than in the control group (25.2 +/- 3.2 and 19.7 +/- 3.2 respectively; p < 0.001), as was free cholesterol (% FC): 9.1 +/- 2.7 and 6.3 +/- 1.5 respectively; p < 0.001. The diagnosis of microalbuminuria (MA) was not associated with changes in lipid transfers. Insulin therapy was associated with lower PLT rates: 23.5 +/- 2.1 versus 26.1 +/- 3.3; p = 0.018. Statin therapy, in turn, was associated with a drop in all lipid transfers - CET 3.5 +/- 0.9; PLT: 23.8 +/- 2.0; TGT: 3.9 +/- 0.8; FCT: 7.4 +/- 1.3 - as compared to the group that was not on statin therapy (CET: 5.9 +/- 2.4; PLT: 26.9 +/- 3.6; TGT: 6.4 +/- 2.2; FCT: 11.1 +/- 2.6). CONCLUSION Type-2 diabetes mellitus increased lipid transfer to HDL particles, whereas statin therapy decreased all lipid transfers. The presence of MA was not associated with changes in lipid transfer.

Avaliação da frutosamina como parâmetro de controle glicêmico na gestante diabética

Objective To evaluate the alternative parameters to monitor glycemia in pregnant women with diabetes studying the relationship between fructosamine testing and self monitoring of blood glucose in pregnant women with diabetes. Materials and methods Serum fructosamine levels and the self monitoring of blood glucose over 14 days before the collection of fructosamine were evaluated in 47 diabetic pregnant women. Results Seventy-one fructosamine levels and 2,238 glucose measurements (CGs) were analysed. Levels of fructosamine correlated with high blood glucose index (HBGI) and the standard deviation of glycemias (r = 0.28; p = 0.021 and r = 0.26; p = 0.03, respectively). The comparison between the mothers of the newborns with appropriated or large birthweight and those who gave birth to small newborns for their gestational age (SGA) showed that the latter had a lower glycemic mean (105 vs. 114 and 119 mg/dL), a higher low blood glucose index (5.8 vs. 1.3 and 0.7) and a higher percentage of hyperglycemias (11 vs. 0 and 0%) even when the fructosamine falls within the reference values (242 vs. 218 and 213 μmol/l). Conclusion The levels of fructosamine can be used as further parameter to aid self monitoring of blood glucose to evaluate hyperglycemias and glycemic variability, however, this can underestimate hypoglycemias in pregnant women carrying small-for-gestational age fetuses.

Transferencias lipídicas hacia HDL en diabéticos tipo 2: asociaciones con microalbuminuria, estatina y insulina

FUNDAMENTO: La diabetes mellitus tipo 2 (DM2) es un factor de riesgo aislado para coronariopatia, principalmente cuando asociado a la microalbuminuria (MA). Alteraciones estructurales y funcionales de las lipoproteinas no estan totalmente aclaradas en ese contexto. OBJETIVO: Evaluar no solo la transferencia de lipidos hacia HDL (T) en pacientes DM2, sino tambien la asociacion tanto con la presencia de la MA como con el tratamiento con estatina o insulina. METODOS: Estudiamos a 33 pacientes con DM2 y 34 controles pareados para edad. Se incubo con plasma una nanoemulsion lipidica artificial radiomarcada con 3H-Triglicerido (TG) y 14C-colesterol libre (CL) o 3H-colesterol esterificado (CE) y 14C-fosfolipido (FL). Se procedio a la precipitacion de la nanoemulsion y de las lipoproteinas, con excepcion de la HDL, que tuvo su radioactividad contada. RESULTADOS: El valor de TFL (%) resulto mayor en el grupo con DM2 en confrontacion con el grupo-control (25,2±3,2 y 19,7±3,2 respectivamente; p < 0,001); la TCL (%), por su vez, obtuvo los siguientes resultados: 9,1±2,7 y 6,3±1,5 respectivamente; p < 0,001. El diagnostico de MA no se asocio a cambios de la propiedad de transferencia. El uso de la insulina se asocio al menor valor de TFL (%): 23,5±2,1 vs 26,1±3,3; p = 0,018. Ya el uso de la estatina se asocio a la baja del valor de todas las lipoproteinas - TCE (%): 3,5±0,9; TFL (%):23,8±2,0; TTG (%): 3,9±0,8; TCL (%):7,4±1,3 - si comparado al grupo que no usaba estatina (TCE (%):5,9±2,4; TFL (%):26,9±3,6; TTG (%):6,4±2,2; TCL (%):11,1±2,6). CONCLUSIONES: El DM2 aumento la transferencia de lipidos de superficie hacia HDL, mientras que el uso de estatina disminuyo todas las transferencias de lipidos. La presencia de MA no se asocio a las alteraciones de las transferencias de lipidos.BACKGROUND Type-2 diabetes mellitus (T2DM) is an isolated risk factor for coronary artery disease, especially when associated with microalbuminuria (MA). Structural and functional changes in lipoproteins have not yet been fully elucidated in this context. OBJECTIVE To assess lipid transfer (T) to HDL in type-2 diabetic patients and its association with microalbuminuria and treatment with statins or insulin. METHODS Thirty-three patients with type-2 diabetes mellitus and 34 age-matched control subjects were studied. A synthetic cholesterol-rich nanoemulsion radiolabeled with (3)H- triglycerides (TG) and 14C-free cholesterol (FC) or (3)H- cholesteryl ester (CE) and 14C-phospholipids (PL) was incubated with plasma. Both the nanoemulsion and lipoproteins were precipitated, except for HDL, which was counted for radioactivity. RESULTS PLT (%) was higher in the T2DM group than in the control group (25.2 +/- 3.2 and 19.7 +/- 3.2 respectively; p < 0.001), as was free cholesterol (% FC): 9.1 +/- 2.7 and 6.3 +/- 1.5 respectively; p < 0.001. The diagnosis of microalbuminuria (MA) was not associated with changes in lipid transfers. Insulin therapy was associated with lower PLT rates: 23.5 +/- 2.1 versus 26.1 +/- 3.3; p = 0.018. Statin therapy, in turn, was associated with a drop in all lipid transfers - CET 3.5 +/- 0.9; PLT: 23.8 +/- 2.0; TGT: 3.9 +/- 0.8; FCT: 7.4 +/- 1.3 - as compared to the group that was not on statin therapy (CET: 5.9 +/- 2.4; PLT: 26.9 +/- 3.6; TGT: 6.4 +/- 2.2; FCT: 11.1 +/- 2.6). CONCLUSION Type-2 diabetes mellitus increased lipid transfer to HDL particles, whereas statin therapy decreased all lipid transfers. The presence of MA was not associated with changes in lipid transfer.