Simão Augusto Lottenberg

Metabolic syndrome: identifying the risk factors

OBJECTIVES To discuss the metabolic syndrome and identify its risk factors, including in the pediatric age group. SOURCES Indexed review articles. SUMMARY OF THE FINDINGS The metabolic syndrome is characterized by insulin resistance and the presence of risk factors for cardiovascular diseases and diabetes mellitus type 2. Consensus has not yet been reached on its diagnostic criteria. This review presents diagnostic criteria defined by the American Heart Association (US National Cholesterol Education Program), the American Association of Clinical Endocrinologists, the World Health Organization and the International Diabetes Federation and discusses the possibilities of applying them to children. Pathophysiologic features of the syndrome are also covered, principally those related to the perinatal period and childhood. CONCLUSIONS The metabolic syndrome is being diagnosed with ever greater frequency, principally during adolescence. Lifestyle changes, such as to diet and level of physical activity are fundamental to prevention. Treatment with medication and, in extreme cases, with surgery should also be considered, depending on severity and age.

Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls

Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester transfer from the HDL-containing plasma fraction to lipoproteins of lighter densities (apo B-containing LP) and plasma cholesteryl ester transfer protein concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n = 11) and normal controls (n = 10) both in the fasting state and 4 h after a standard milk-shake test meal (50g of fat/m of body surface). The percent of [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL containing preparation incubated for 30 min and the [3H]cholesteryl ester transfer was measured upon precipitation of apo B-containing lipoproteins with dextran sulphate/MgCl2 following a 2 h period of plasma incubation with [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma triglyceride concentration and to a similar extent in diabetics and in normal controls. Both a HDL-[3H]cholesteryl ester synthesis and transfer rates were equally stimulated in diabetics and in controls. When data were expressed by the concentration of plasma triglycerides, cholesteryl ester formation and transfer rates were similar in the alimentary and fasting periods, and when expressed per apo B concentration, cholesteryl ester transfer rates rose during the alimentary period in both diabetics and controls indicating that there was a net gain of cholesteryl ester per apo B lipoprotein. Plasma CETP mass, and neutral lipid transfer activity were similar in diabetics and normal controls demonstrating that the reverse transport of cholesterol through the apo B lipoprotein pathway is not altered in normotriglyceridemic Type II diabetics.

HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus.

PURPOSE In this study we analyzed the role played by aerobic exercise training in the plasma lipoprotein profile, prebeta 1-HDL concentration, and in the in vitro HDL3 ability to remove cholesterol from macrophages and inhibit LDL oxidation in type 2 diabetes mellitus (DM) patients and control subjects, in the fasting and postprandial states. METHODS Healthy controls (HTC, N = 11; 1 M/10 F) and subjects with type 2 diabetes mellitus (DMT, N = 11; 3M/8F) were engaged in a 4-month aerobic training program, and compared with a group of sedentary subjects with type 2 diabetes mellitus (DMS, N = 10; 4 M/6 F). All groups were submitted to an oral fat load test to analyze all parameters, both at the beginning of the investigation protocol (basal) and at the end of the study period (final). RESULTS Exercising did not modify body weight, BMI, plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (TG), glucose, insulin, or HOMA-IR, but it reduced the waist circumference. The HDL3 composition did not change, and its ability to remove cell cholesterol was unaltered by aerobic training. In DMT but not in HTC, aerobic training improved 15% the HDL3 protective effect against LDL maximal oxidation rate in the fasting state, and reduced 24% the plasma prebeta 1-HDL concentration in the postprandial state, suggesting an enhanced prebeta 1-HDL conversion into larger, more mature HDL particles. In this regard, regular aerobic exercise enriched HDL2 with TG in the fasting and postprandial states in HTC and in the fasting phase in DMT. CONCLUSION Our results show that aerobic exercise training in diabetes mellitus improves the HDL efficiency against LDL oxidation and favors HDL maturation. These findings were independent of changes in insulin resistance and of the rise of plasma HDL cholesterol concentration.

Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states.

Hypercholesterolemic women (n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides. When transfer data were related to the plasma concentration of apo B, the gain of cholesteryl ester by the triglyceride-containing particles (VLDL + LDL) also increased in the postprandial period to a similar extent for both diets. Cholesteryl ester transfer protein (CETP) concentration measured by radioimmunoassay was similar during both experimental diets, although greater in the postprandial period for the PUFA diet. The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester (CE) was the plasma triglyceride concentration, that is, the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles (VLDL + LDL). In contrast, the fatty acid composition of these particles had less effect on CETP-mediated CE transfer.

Síndrome metabólica: identificando fatores de risco

OBJECTIVES: To discuss the metabolic syndrome and identify its risk factors, including in the pediatric age group. SOURCES: Indexed review articles. SUMMARY OF THE FINDINGS: The metabolic syndrome is characterized by insulin resistance and the presence of risk factors for cardiovascular diseases and diabetes mellitus type 2. Consensus has not yet been reached on its diagnostic criteria. This review presents diagnostic criteria defined by the American Heart Association (US National Cholesterol Education Program), the American Association of Clinical Endocrinologists, the World Health Organization and the International Diabetes Federation and discusses the possibilities of applying them to children. Pathophysiologic features of the syndrome are also covered, principally those related to the perinatal period and childhood. CONCLUSIONS: The metabolic syndrome is being diagnosed with ever greater frequency, principally during adolescence. Lifestyle changes, such as to diet and level of physical activity are fundamental to prevention. Treatment with medication and, in extreme cases, with surgery should also be considered, depending on severity and age.

The impact of dietary fatty acids on macrophage cholesterol homeostasis

The impact of dietary fatty acids in atherosclerosis development may be partially attributed to their effect on macrophage cholesterol homeostasis. This process is the result of interplay between cholesterol uptake and efflux, which are permeated by inflammation and oxidative stress. Although saturated fatty acids (SAFAs) do not influence cholesterol efflux, they trigger endoplasmic reticulum stress, which culminates in increased lectin-like oxidized LDL (oxLDL) receptor (LOX1) expression and, consequently, oxLDL uptake, leading to apoptosis. Unsaturated fatty acids prevent most SAFAs-mediated deleterious effects and are generally associated with reduced cholesterol efflux, although α-linolenic acid increases cholesterol export. Trans fatty acids increase macrophage cholesterol content by reducing ABCA-1 expression, leading to strong atherosclerotic plaque formation. As isomers of conjugated linoleic acid (CLAs) are strong PPAR gamma ligands, they induce cluster of differentiation (CD36) expression, increasing intracellular cholesterol content. Considering the multiple effects of fatty acids on intracellular signaling pathways, the purpose of this review is to address the role of dietary fat in several mechanisms that control macrophage lipid content, which can determine the fate of atherosclerotic lesions.

Home blood glucose monitoring in type 1 diabetes mellitus

OBJETIVO: Identificar cual de los dos esquemas de monitorizacion propuestos posibilita realizar un mejor control metabolico, en diabeticos del tipo1, durante los 12 meses de participacion en grupos educativos. METODO: Ensayo clinico cruzado con 21 pacientes divididos en dos grupos y sometidos a dos diferentes esquemas de monitorizacion. La efectividad de los esquemas fue evaluada por medio de la HbA1c. La variacion de los promedios de HbA1c fue analizada con la prueba de Friedman. RESULTADOS: Durante todo el estudio la variacion de los promedios de HbA1c, para el grupo A, fue de 8,48(±1,00) la 7,37(±0,99) y de 9,89(±0,86) la 8,34(±1,06) para el grupo B. Los analisis de la variacion de la HbA1c colocaron en evidencia una reduccion significativa (p<0,05) en los dos grupos, en los 3 periodos evaluados: primeros y ultimos 6 meses y durante los 12 meses de estudio. CONCLUSIONES: Los dos esquemas mejoraron el control metabolico y el esquema antes de las comidas fue mas efectivo.OBJECTIVE To determine which of two simplified blood glucose monitoring schemes promotes better metabolic control in type 1 diabetic patients during 12 months of participation in educational groups. METHODS A crossover clinical trial involving 21 patients divided into two groups was conducted. They were submitted to a two monitoring schemes: 2 alternate daily preprandial measurements and 2 alternate daily pre-and postprandial measurements. The effectiveness of the schemes was evaluated based on HbA1c. Variations in mean HbA1c were analyzed by Friedman test. RESULTS The groups were homogenous in terms of sociodemographic and clinical variables (p>0.05). Mean HbA1c levels ranged from 8.48 (+/-1.00) to 7.37 (+/-0.99) over time in Group A and from 9.89 (+/-0.86) to 8.34 (+/-1.06) in Group B. The analysis of the HbA1c showed a significant reduction in the first and last 6 months and over the 12 months of the study in two groups (p<0.05). The preprandial scheme demonstrated the largest number and highest percentage of significant drops in HbA1c. CONCLUSIONS The two monitoring improved the metabolic control and the preprandial scheme was more effective.

A relação entre polifarmácia, complicações crônicas e depressão em portadores de Diabetes Mellitus Tipo 2

Fueron objetivos de este estudio: caracterizar a la polifarmacia entre portadores de Diabetes Mellitus tipo 2 (DM2) y correlacionar la polifarmacia y el numero de complicaciones de la DM2 con indicadores de depresion (Inventario de Depresion de Beck [IDB] y cortisol urinario [CORT]). La muestra fue integrada por 40 pacientes de la Liga de Diabetes del HCFM-USP evaluados respecto de los indicadores de depresion (CORT e IDB) y tambien en cuanto a la practica de polifarmacia y numero de complicaciones de la DM2. Los resultados mostraron que los medicamentos utilizados fueron: antidiabeticos orales, insulinas, antihipertensivos, diureticos, antilipemiantes y tromboliticos. Dentro del grupo estudiado, 75% de los pacientes utilizaban diariamente entre 5 y 8 medicamentos, un 12,5% de la muestra hacia uso de 8 medicamentos/dia o mas; todos hicieron como minimo tres tomas diarias, el 60% presentaba entre 1 y 3 complicaciones de la DM2 y el 22,5% presentaba 3 o mas. La correlacion entre los indicadores de depresion (IDB y CORT) y el numero de medicamentos y de complicaciones de la DM2 no fue estadisticamente significativa. Sin embargo, hubo correlacion positiva entre CORT y la cantidad de tomas diarias de medicamentos (Spearman, r=0.319, p=0.019).The objectives of this study were: to characterize the polipharmacy in subjects with type 2 diabetes mellitus (DM2) and to verify the correlation between polipharmacy and number of medications for DM2 complications with depression indicators (Beck Depression inventory (BDI) and urinary cortisol (CORT) levels). A sample composed of 40 patients with DM2 from the Diabetes League of HCFM-USP was analyzed for depression indicators (CORT and BDI) in addition to evaluation for polipharmacy and number of DM2 complications. The results showed oral hypoglycemic agents, insulins, antihypertensives, diuretics, lipid-lowering drugs and thrombolytics are the most frequent medications used. In this sample, 75% used from 5 to 8 medicines daily and 12.5% used more than eight medicines/day; all of them used to take each medication at least 3 times daily. Between 1 and 3 DM2 complications were observed in 60% of the individuals and 22.5% showed more than 3 DM2 complications. No significant correlations were observed between depression indicators (BDI and CORT), number of medications and DM2 complications. However, positive correlation was observed between CORT and daily frequency of medication (Spearman, r = 0.319, p = 0.019).

Association of reduced zinc status with poor glycemic control in individuals with type 2 diabetes mellitus

This study evaluated the relationship between the zinc-related nutritional status and glycemic and insulinemic markers in individuals with type 2 diabetes mellitus (T2DM). A total of 82 individuals with T2DM aged between 29 and 59 years were evaluated. The concentration of zinc in the plasma, erythrocytes, and urine was determined by the flame atomic absorption spectrometry method. Dietary intake was assessed using a 3-day 24-h recall. In addition, concentrations of serum glucose, glycated hemoglobin percentage, total cholesterol and fractions, triglycerides, and serum insulin were determined. The insulin resistance index (HOMA-IR) and β-cell function (HOMA- β) were calculated. The markers of zinc status (plasma: 83.3±11.9μg/dL, erythrocytes: 30.1±4.6μg/g Hb, urine: 899.1±622.4μg Zn/24h, and dietary: 9.9±0.8mg/day) were classified in tertiles and compared to insulinemic and glycemic markers. The results showed that lower zinc concentrations in plasma and erythrocytes, as well as its high urinary excretion, were associated with higher percentages of glycated hemoglobin, reflecting a worse glycemic control in individuals with T2DM (p<0.05). Furthermore, there was a significant inverse correlation between plasma zinc levels and glycated hemoglobin percentage (r=-0.325, p=0.003), and a positive correlation between urinary zinc excretion and glycemia (r=0.269, p=0.016), glycated hemoglobin percentage (r=0.318, p=0.004) and HOMA-IR (r=0.289, p=0.009). According to our study results, conclude that T2DM individuals with reduced zinc status exhibited poor glycemic control.

The relationship between polipharmacy, chronic complications and depression in individuals with Type 2 Diabetes Mellitus

Fueron objetivos de este estudio: caracterizar a la polifarmacia entre portadores de Diabetes Mellitus tipo 2 (DM2) y correlacionar la polifarmacia y el numero de complicaciones de la DM2 con indicadores de depresion (Inventario de Depresion de Beck [IDB] y cortisol urinario [CORT]). La muestra fue integrada por 40 pacientes de la Liga de Diabetes del HCFM-USP evaluados respecto de los indicadores de depresion (CORT e IDB) y tambien en cuanto a la practica de polifarmacia y numero de complicaciones de la DM2. Los resultados mostraron que los medicamentos utilizados fueron: antidiabeticos orales, insulinas, antihipertensivos, diureticos, antilipemiantes y tromboliticos. Dentro del grupo estudiado, 75% de los pacientes utilizaban diariamente entre 5 y 8 medicamentos, un 12,5% de la muestra hacia uso de 8 medicamentos/dia o mas; todos hicieron como minimo tres tomas diarias, el 60% presentaba entre 1 y 3 complicaciones de la DM2 y el 22,5% presentaba 3 o mas. La correlacion entre los indicadores de depresion (IDB y CORT) y el numero de medicamentos y de complicaciones de la DM2 no fue estadisticamente significativa. Sin embargo, hubo correlacion positiva entre CORT y la cantidad de tomas diarias de medicamentos (Spearman, r=0.319, p=0.019).The objectives of this study were: to characterize the polipharmacy in subjects with type 2 diabetes mellitus (DM2) and to verify the correlation between polipharmacy and number of medications for DM2 complications with depression indicators (Beck Depression inventory (BDI) and urinary cortisol (CORT) levels). A sample composed of 40 patients with DM2 from the Diabetes League of HCFM-USP was analyzed for depression indicators (CORT and BDI) in addition to evaluation for polipharmacy and number of DM2 complications. The results showed oral hypoglycemic agents, insulins, antihypertensives, diuretics, lipid-lowering drugs and thrombolytics are the most frequent medications used. In this sample, 75% used from 5 to 8 medicines daily and 12.5% used more than eight medicines/day; all of them used to take each medication at least 3 times daily. Between 1 and 3 DM2 complications were observed in 60% of the individuals and 22.5% showed more than 3 DM2 complications. No significant correlations were observed between depression indicators (BDI and CORT), number of medications and DM2 complications. However, positive correlation was observed between CORT and daily frequency of medication (Spearman, r = 0.319, p = 0.019).