Vitamin E status in gold-thioglucose-treated obese mice: the influence of weight loss

The influence of weight-loss and dietary vitamin E supplementation on plasma vitamin E status has been evaluated in Gold-thioglucose induced hypothalamic obese mice. They were submitted for two weeks to different dietary regimens: a normal energy-normal vitamin E diet (standard diet), a low energy-normal vitamin E diet (protein sparing modified fast (PSMF)-diet) and a no energy-no vitamin E diet (total starvation) respectively. Plasma vitamin E levels were significantly higher in the PSMF-treated group (P less than 0.01) but remained constant in the total fast group as compared to obese controls. Plasma vitamin E/cholesterol ratio (being increased (P less than 0.01) in PSMF-mice and decreased (P less than 0.01) in total fast mice) was strongly correlated with dietary vitamin E/fat ratio. These results suggest that dietary vitamin E supplementation can prevent plasma vitamin E to decrease during rapid weight-loss and that vitamin E/fat ratio is the main parameter to evaluate the dietary adequacy of vitamin E supplementation.     

Apolipoprotein E polymorphism and hyperlipoproteinemia in obesity

The purpose of this study is to elucidate the relationship between apolipoprotein (apo) E polymorphism and plasma lipid profiles and the frequency of hyperlipoproteinemia (HLP) in obesity. Eighty-seven obese subjects with 131 percent of ideal body weight (mean) were studied. One hundred and thirty-two nonobese subjects with 105 percent of ideal body weight were also selected as the controls. There was no significant difference in apo E allele and phenotype frequencies between the obese and nonobese subjects. The frequency of HLP was 100 percent in obese subjects with apo E2 and/or apo E4, whereas it was 47.3 percent in obese subjects with the common apo E3/3 phenotype. In obesity apo E2 was associated with increased plasma triglyceride (TG) and apo E, and decreased plasma high density lipoprotein (HDL) cholesterol (type III and IV HLP), whereas apo E4 was associated with increased plasma TG, total cholesterol, and apo E (type IIa, IIb, IV and V HLP). These results indicate that obese subjects with apo E2 and/or E4 were more susceptible to HLP than obese subjects with the common apo E3/3 phenotype. It is concluded that apo E2 and/or E4 are closely related to HLP in obesity and thus may be one factor linking obesity with cardiovascular disease.     

Leptin and its relation to obesity and insulin in the SHR/N-corpulent rat,a model of type II diabetes mellitus

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p < 0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r = 0.73, p < 0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r = 0.54, p < 0.05). There was also a significant positive correlation between plasma leptin and plasma insulin in the entire group (r = 0.70, p < 0.01). However, this relationship was significant only for lean rats but not for obese rats (r = 10.59, p < 0.05 for lean rats, and r = 0.23, p = NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r = 0.75, p < 0.05), total cholesterol (r = 0.63, p < 0.05), and triglyceride (r = 0.67, p < 0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.     

Associations Between Antioxidant Vitamin Status,Dietary Intake,and Retinol-binding Protein 4 Levels in Prepubertal Obese Children After 3-month Weight Loss Therapy

Objective:Adiposity is associated with increased oxidative stress, leading to changed fat-soluble vitamin concentrations. The aim of this study was to determine whether weight loss alters fat-soluble vitamin status and whether these alterations are associated with dietary intake, anthropometric parameters and adipokines in obese children.Methods:Vitamin A and E concentrations were measured using high-pressure liquid chromatography in 60 obese children before and after weight loss therapy. Retinol-binding protein 4 (RBP4), leptin, soluble leptin receptor (sOB-R), and high molecular weight adiponectin concentrations were determined by immunoenzymatic assays.Results:The intake of vitamin E was lower in obese children with weight loss after therapy (p=0.038). In this group, an increase was found in the vitamin A/lipids (p=0.022) and the vitamin E/lipids (p=0.008) ratios but due to the reduction in triglyceride levels. In the obese group, changes in vitamin E level were positively correlated with changes in dietary vitamin E (p=0.017) and the leptin/sOB-R ratio (p=0.046). Changes in vitamin A level were positively correlated with changes in dietary vitamin A (p=0.001) and RBP4 concentration (p=0.023). Associations between changes in RBP4 level with the changes in body mass index (BMI) (p=0.011) and total cholesterol concentration (p=0.023) but not with changes in vitamin A concentration were found in the obese after therapy.Conclusion:An increased risk of vitamin E deficiency may occur in children losing weight during lifestyle intervention. Changes in BMI value may influence changes in RBP4 concentrations and consequently the vitamin A status in obese children after therapy.     

Postprandial lipoprotein metabolism in normal and obese subjects: comparison after the vitamin A fat-loading test

Abnormalities in fasting lipid and lipoprotein levels are known to occur in obesity and other hyperinsulinemic states. However, postprandial lipoprotein metabolism has not been studied systematically in obese subjects using sensitive techniques to distinguish between triglyceride-rich lipoprotein particles derived from the intestine and the liver. In the present study the vitamin A fat-loading test was used to label intestinally derived triglyceride-rich lipoprotein particles in the postprandial state. Lipid parameters in seven normolipidemic obese subjects [body mass index, 43.7 +/- 2.81 kg/m2 (mean +/- SEM)] were compared to those in eight matched normal weight controls (body mass index, 23.6 +/- 0.72 kg/m2) during the 24-h period following ingestion of a mixed meal with a high fat content to which vitamin A had been added. Although subjects were selected for normal fasting lipid levels, in the obese group fasting triglycerides were significantly higher (1.35 +/- 0.12 vs. 0.68 +/- 0.08 mmol/L; P less than 0.0005) and high density lipoprotein (HDL) cholesterol was lower (0.94 +/- 0.08 vs. 1.35 +/- 0.11 mmol/L; P less than 0.01). The obese subjects had a greater postprandial triglyceride response to the test meal (P less than 0.05). The cumulative increment in total plasma triglycerides was 3.35-fold greater in obese than control subjects, while that of retinyl ester was only 1.63-fold greater, suggesting that a significant portion of the postprandial triglyceride response is due to endogenous hepatic lipoproteins. Postprandial plasma triglyceride and retinyl ester increment correlated with basal triglycerides (r = 0.72; P less than 0.005 and r = 0.57; P less than 0.03, respectively) and negatively with fasting HDL (r = -0.51; P less than 0.05 and r = -0.60; P less than 0.02, respectively). In the obese, the HDL triglyceride content increased maximally 4 h postprandially (4.1% to 6.1%; P less than 0.005) and phospholipid at 12 h (25.8% to 28.7%; P less than 0.05), with lower cholesteryl ester (21.1% to 17.5%; P less than 0.002) at 8 h, reflecting exchange of surface and core lipids with triglyceride-rich particles after the meal. In obese and control subjects the magnitude of HDL triglyceride enrichment after the meal correlated positively with the postprandial triglyceride increment (r = 0.74; P less than 0.007) and negatively with the fasting HDL cholesterol concentration (r = -0.80; P = 0.002). We conclude that even normolipidemic obese subjects have greater postprandial lipemia and triglyceride enrichment of HDL after ingestion of a high fat meal.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of plasma lipid profile oxysterols and vitamin E concentration in morbidity obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of arterial hypertension and non-insulin dependent diabetes mellitus. The aim of the study was to assess plasma concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG) and two parameters of oxidation stress--vitamin E and oxysterols, in morbidly obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus. Studies were performed in 37 morbidly obese patients divided into three groups: group I--without coexisting diseases, group II--with arterial hypertension, and group III--with arterial hypertension and non-insulin dependent diabetes mellitus. In all groups there was an increase in TG concentration, a decrease in HDL-cholesterol level, and normal values of TC and LDL-cholesterol. The concentrations of 7-hydroxycholesterols (7-OH) in group II (602.65 +/- 264.46 ng/ml) and group III (570.94 +/- 210.59 ng/ml) were significantly higher compared to that in group I (336.09 +/- 220.74 ng/ml). There were no differences between groups in concentrations of 7-ketocholesterols (7-K), TC, HDL-cholesterol, LDL-cholesterol, TG, vitamin E and vitamin E/(TC + TG) ratio. In all groups TC concentration correlated positively with TG concentration, and negatively with vitamin E/(TC + TG) ratio. Moreover, the positive correlation between TG and HDL-cholesterol concentrations, and negative correlation between plasma vitamin E and 7-K concentrations were demonstrated. In conclusion, although the study demonstrates similar disturbances in lipid profile and oxidation stress parameters in all groups, with significant differences in 7-OH only, the role of cholesterol oxidation products in pathogenesis of arterial hypertension and non-insulin dependent diabetes mellitus in morbidly obese patients cannot be excluded.     

Serum 25-hydroxyvitamin D is associated with insulin resistance independently of obesity in children ages 5–17

AimTo determine the association of vitamin D with insulin resistance and obesity in children.MethodsA total of 92 obese and 58 non-obese children aged 5–17 years were evaluated. Data were collected related to anthropometric (weight, height), and biochemical parameters (fasting plasma glucose, serum insulin, serum 25-hydroxyvitamin D, lipid profile, vitamin B12, parathormone) and physical examination (blood pressure, acanthosis nigricans, stria, lipomastia). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA). HOMA-IR = fasting insulin level (μU/ml) × fasting glucose (mg/dL)/405. A HOMA-IR value >2.5 was defined as insulin resistance.ResultsAccording to the US Endocrine Society classification, vitamin D deficiency (0−20 ng/ml) was determined at significantly higher rates in the obese group than in the control group (p < 0.001). The rate of subjects with a vitamin D level of 20−30 ng/ml was significantly lower in the obese group than in the control group (p < 0.001) Within the obese group a statistically significant difference was determined between the insulin resistant and non-insulin resistant groups in respect of serum 25-hydroxyvitamin D levels (p = 0.001) and vitamin B12 levels (p = 0.001). A significant negative correlation was determined between serum 25-hydroxyvitamin D and HOMA-IR (r=−0.256, p = 0.016) and insulin (r = −0.258, p = 0.015). The systolic blood pressure (p = 0.001) and diastolic blood pressure (p = 0.003) values were significantly different in the control and obese groups. A statistically significant difference was determined between the control and obese groups in terms of the levels of insulin, HOMA-IR, HbA1c, cortisol, LDL, total cholesterol, HDL, triglyceride, hemoglobin, MCV, MPV, and calcium.ConclusionThe prevalence of vitamin D deficiency was higher in obese children compared to normal-weight and overweight children. Serum 25(OH)D levels showed a negative correlation with insulin and HOMA-IR. Serum 25(OH)D is associated with insulin resistance independently of obesity.     

The cholesterol saturation of bile and its reduction by chenodeoxycholic acid in massively obese patients

Massively obese patients are at high risk for developing cholesterol gallstones. The objectives of this study were to determine the influence of massive obesity on the cholesterol saturation of bile, and to examine the effect of massive obesity on the ability of chenodeoxycholic acid to decrease biliary cholesterol saturation. Gallbladder bile collected at surgery from massively obese patients was significantly more saturated with cholesterol than bile from non-obese patients who were matched for age, sex and gallstone status (P less than 0.01). Median biliary cholesterol saturation index values for groups of subjects were: no gallstones-not obese (0.83); no gallstones-obese (1.14); gallstones-not obese (1.08); gallstones-obese (1.37). Furthermore, a 5-week course of chenodeoxycholic acid (6 mg/kg/day) was less effective in reducing biliary cholesterol saturation in massively obese patients. The bile of 4 of 10 obese patients remained supersaturated, compared to only one of 10 non-obese patients. These results indicate that biliary cholesterol saturation is raised in massive obesity and that in this condition, the biliary lipid response to chenodeoxycholic acid is diminished. This may explain why obese patients have a relatively poor response to gallstone dissolution therapy with this bile acid.     

Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease

The vitamin E status of 146 adults with chronic liver disease was assessed by estimating both their serum vitamin E concentration and the ratio of serum vitamin E to serum cholesterol concentration. Low levels of vitamin E occurred most frequently in patients with primary biliary cirrhosis and other forms of chronic cholestatic liver disease. When a serum vitamin E concentration of 12.3 mumol/l (mean-2 SD of a control population) was taken as the lower limit of normal, 44% of patients with primary biliary cirrhosis and 32% with other chronic cholestatic liver disease had a reduced concentration, indicating a biochemical deficiency of vitamin E. If a vitamin E/total cholesterol ratio of 2.35 mumol/mmol was taken as the lower limit of normal, then 64% and 43% of patients with primary biliary cirrhosis and other chronic cholestatic liver disease, respectively, had a biochemical deficiency of vitamin E. Of the patients with chronic cholestasis and a serum bilirubin concentration greater than 100 mumol/l, 91% had a reduced vitamin E/cholesterol ratio. Twelve patients with primary biliary cirrhosis and severe vitamin E deficiency (serum vitamin E less than 5.0 mumol/l and a vitamin E/cholesterol ratio less than 1.0 mumol/mmol) underwent extensive neurological investigation. Five had a mild mixed sensorimotor peripheral neuropathy, which was not, however, typical of the neurological syndrome associated with vitamin E deficiency. In patients with severe biochemical deficiency of vitamin E (less than 5 mumol/l and less than 1 mumol/mmol total cholesterol), administration of large oral doses of vitamin E only increased serum concentrations to within the normal range in one patient; in the others even weekly parenteral administration over a 3-month period did not correct deficiency. In patients with less severe biochemical deficiency, the serum vitamin E concentration and vitamin E/total cholesterol ratio were restored to normal by oral or intramuscular supplements of the vitamin.     

Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.     

Association of obesity and distribution of obesity with glucose tolerance and cardiovascular risk factors in the elderly.

The association of obesity and fat distribution with glucose tolerance and cardiovascular risk factor levels were investigated in a population-based study in East Finland including 396 non-diabetic men and 673 women aged from 65 to 74 years. Obese men and women (BMI greater than 27 kg/m2) had higher levels (P less than 0.001) of fasting and 2 h plasma glucose and insulin as well as total triglycerides and diastolic blood pressure, and lower levels of HDL cholesterol than normal weight men and women. Central fat distribution (the highest vs. the lowest tertile of waist-hip ratio) was associated independently of obesity with high fasting glucose (5.7 vs. 5.5 mmol/l in non-obese subjects, 5.9 vs. 5.7 mmol/l in obese subjects, P less than 0.05) and insulin levels (13.7 vs. 10.6 mU/l in non-obese subjects, 18.4 vs. 15.6 mU/l in obese subjects, P less than 0.01) and with adverse changes (P less than 0.05) in lipid and lipoprotein levels (triglycerides: 1.59 vs. 1.41 mmol/l in non-obese subjects, 1.92 vs. 1.69 mmol/l in obese subjects; HDL cholesterol: 1.33 vs. 1.43 mmol/l in non-obese subjects, 1.20 vs. 1.32 mmol/l in obese subjects). There were no marked differences in metabolic aberrations related to obesity between men and women. However, the association between waist-hip ratio and risk factors was non-linear in men whereas it was linear in women. In conclusion, obesity per se rather than its distribution was a more significant determinant of glucose and insulin as well as total triglyceride and HDL cholesterol levels in elderly subjects.     

Serum cholesterol and vitamins A and E in juvenile chronic arthritis

Serum total cholesterol is decreased during acute infections and in adults with rheumatoid arthritis, probably partly because of enhanced lipid peroxidation. Oxidative stress also causes augmentation of inflammation and tissue damage in arthritic synovium. Therefore, concentrations of serum total cholesterol and the antioxidant vitamins A and E were studied in 125 children with juvenile chronic arthritis. Total serum cholesterol was significantly lower in the patients than in healthy children in most age groups and correlated with the markers of disease activity, haemoglobin and the erythrocyte sedimentation rate. In age- and sex-adjusted stepwise multiple linear regression, serum zinc had a significant predictive value for cholesterol. The vitamin A concentrations in the sera of the patients was virtually the same as in the healthy controls, though serum vitamin E concentrations were low (22.8 +/- 15.2 vs 30.5 +/- 4.3 mumol/l, p less than 0.001). The deficiency in vitamin E was not compensated for by another lipoperoxide antioxidant, glutathione peroxidase. Only serum cholesterol had an independent explanatory significance for vitamin E in multiple linear regression analysis (partial correlation 0.554, p less than 0.001). It is suggested that low vitamin E and impairment of the anti-oxidant protection further contribute to low serum cholesterol values in JCA.     

Bone structure and calcium metabolism in obese Zucker rats.

Obesity is associated with altered bone mass. However, reports on bone status in obesity are inconsistent. Increased or normal bone mass was reported in obese adults but decreased bone mineral content was described in obese children. Therefore we evaluated the obese fa/fa rat as a possible model to assist in studies of bone metabolism in obesity. Obese and lean 14-week-old male rats underwent 24 h balance studies for calcium, magnesium and phosphate. Plasma calcium, magnesium, phosphate, immunoreactive parathyroid hormone, urinary cAMP (cyclic adenosine monophosphate) and femur bone histomorphometry were also analysed. Obese rats were heavier and had higher plasma insulin, cholesterol and triglycerides levels (P less than 0.05). A comparable positive balance for calcium, magnesium and phosphate was found in obese and lean rats. Total plasma calcium was higher in the obese, but albumin corrected calcium and plasma magnesium, phosphate and glucose were similar to the lean. In contrast to human obesity, obese rats were hypercalciuric, hypermagnisuric and hyperphosphaturic (P less than 0.05). iPTH and urinary cAMP were higher in the obese. Femora of fa/fa rats were shorter and lighter. Their bone osteoid surface and bone calcium content were similar to controls. Femora metaphysis in the obese had increased number of trabeculae, decreased trabecular width and higher erosion surface/bone surface ratio. Their diaphysis had increased cortical area/bone area and cortical width/bone width ratios and decreased medullary area. In summary, obese rats have higher iPTH, are hypercalciuric and have decreased bone mass. These last two observations differ from what is described in adult human obesity. Therefore, the obese fa/fa rat is of limited assistance in studies of bone status in adult human obesity. It might be of help in studies of bone metabolism in juvenile obesity.     

Fasting ghrelin levels are not elevated in children with hypothalamic obesity

Morbid obesity is a common problem after damage to the hypothalamus. Hypothalamic dysfunction is also thought to underlie the obesity that is typical of Prader-Willi syndrome. Elevated fasting levels of the appetite-stimulating hormone ghrelin have been reported in Prader-Willi syndrome. The aim of this study was to determine whether fasting ghrelin levels are increased in children with hypothalamic obesity. Fasting total ghrelin levels were compared in three groups: normal-weight controls (n = 16), obese controls (n = 16), and patients with hypothalamic obesity (n = 16). Obese children had lower fasting total ghrelin levels than normal controls, but there was no difference between the fasting total ghrelin level in obese controls and children with hypothalamic obesity (P = 0.88). These data suggest that it is unlikely that an elevation in fasting total ghrelin is responsible for the obesity that occurs after hypothalamic damage. Therapeutic interventions aimed at reducing fasting total ghrelin may prove ineffective in controlling weight gain in this group.     

Effects of vitamin A and ethanol on liver plasma membrane fluidity

To study possible mechanisms whereby vitamin A and ethanol may affect liver plasma membranes, rats were fed liquid diets containing either 6 international units of vitamin A per kcal or 5 times more, with or without ethanol (36% of total energy as isocaloric substitution for carbohydrate). Vitamin A supplementation resulted in 2- to 3-fold increases of liver plasma membrane free retinol (p less than 0.005) and retinyl esters (p less than 0.001), particularly esters of palmitate and oleate, whereas cholesterol esters did not change. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene revealed decreased fluidity as measured by an increase in fluorescence polarization which correlated significantly with retinyl palmitate plus oleate content in membranes. In rats fed ethanol chronically, we first verified our previous observation of a decrease in liver plasma membrane fluorescence polarization. We now find this effect to be associated with (and possibly due to) an increase of cholesterol ester content. In linear regression analysis, the change in fluorescence polarization correlated positively with vitamin A (p less than 0.02) and negatively with cholesterol ester contents (p less than 0.001). Ethanol feeding partially offset the effect of vitamin A supplementation on fluorescence polarization. We conclude from these observations that liver plasma membranes contain a significant amount of vitamin A, that vitamin A supplementation increases membrane fluorescence polarization and that chronic ethanol administration can interfere with this effect.     

Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: A comparison of older with young men

In this study, plasma lipids, lipoproteins and markers of oxidant/antioxidant status were investigated in young (n = 45) and older (n = 40) obese men and compared to those in young (n = 65) and older (n = 55) normal weight controls. The purpose was to determine whether obesity exacerbates or not lipid, lipoprotein abnormalities and oxidative stress in older men.Our findings showed that all obese patients had increased plasma triglyceride, cholesterol, LDL-cholesterol, -triglyceride and HDL-triglyceride levels concentrations compared to controls (P < 0.01). However, the younger obese men had relatively larger and accentuated changes in plasma lipids and lipoproteins than the older patients. Additionally, total antioxidant capacity (ORAC), vitamins C and E were lower while hydroperoxides and carbonyl proteins were higher in young and older obese patients compared to their respective controls (P < 0.001). Erythrocyte antioxidant SOD and catalase activities were enhanced in obese young patients, but reduced in obese older men. Glutathione peroxidase activity was low in obesity irrespective of age. In multiple regression analysis, BMI significantly predicted total cholesterol, LDL-C, LDL-TG and HDL-TG (P < 0.0001). These relationships were not modified by age. BMI alone was a not a significant predictor for ORAC, vitamins C, E, catalase and Glutathione peroxidase. However, the interaction BMI–age significantly predicted these parameters and explained 28–45% of their changes. BMI was a significant predictor of SOD, carbonyl proteins and hydroperoxides. This effect became more significant (P < 0.0001) and worsened with BMI–age interaction.In conclusion, lipoprotein metabolism and oxidant/antioxidant status are altered in obesity irrespective of age. However, obesity-related lipid and lipoprotein alterations were attenuated while oxidative stress was aggravated in older adults.     

Prevalence of malnutrition and associated metabolic risk factors for cardiovascular disease in older adults from Northwest Mexico

This cross-sectional study assessed the prevalence of malnutrition and several metabolic risk factors for cardiovascular disease in 287 apparently healthy older adults from Northwest Mexico. Also, the impact of overweight and obesity on metabolic risk factors was assessed. Nutritional status was determined using serum albumin levels and anthropometry. Vitamin status was also assessed. Metabolic risk factors for cardiovascular disease were evaluated. The prevalence of undernutrition was 15.3%. Also, vitamin E deficiency was common (18%). On the contrary, 44.9% of men and women were in overweight and 24% were obese. A 50.9% of the older adults had hypertension, 52.6% hypercholesterolemia (HC), 38.3% hypertriglyceridemia (HTG), 26.1% impaired fasting glucose and 26.1% impaired glucose tolerance (IGT). HC and low-density-lipoprotein-cholesterol (LDL-C) were significantly more prevalent in women than in men. Mean adjusted values of fasting glucose, high-density-lipoprotein-cholesterol (HDL-C), total cholesterol (TC)/HDL-C ratio ≥5, triglycerides (TG) and diastolic blood pressure (DBP) were significantly higher in subjects with body mass index (BMI) ≥ 25.0 kg/m². Undernutrition, obesity and vitamin E deficiency, as well as several metabolic risk factors for cardiovascular disease coexisted in this studied group. Overweight and obesity were the most prevalent findings. BMI ≥ 25 kg/m² was the common factor explaining most of the metabolic abnormalities. However, due to the sample size and the design of the study, the results must be seen with caution and cannot be generalized.     

Disparate cardiovascular effects of obesity and arterial hypertension

Since obesity and essential hypertension frequently coexist, a study was designed to analyze some of their cardiovascular effects. Twenty-eight obese patients, half of whom were normotensive and half with established hypertension, were matched for mean arterial pressure with 28 corresponding lean subjects. Systemic and renal hemodynamics, intravascular volume, plasma renin activity, and circulating catecholamine levels were measured. Obese patients had increased cardiac output (p less than 0.001), stroke volume (p less than 0.001), central blood volume (p less than 0.02), plasma and total blood volume (p less than 0.01), and decreased total peripheral resistance (p less than 0.001). In contrast, cardiac output, central blood volume, and stroke volume of hypertensive patients were normal, but they had increased total peripheral (p less than 0.001) and renal vascular resistance (p less than 0.001) and a contracted intravascular volume. Left ventricular stroke work was elevated to a similar level in obesity (p less than 0.001) and hypertension (p less than 0.02), but the increase was caused by an expanded stroke volume in the former and by an increase in systolic pressure in the latter. It is concluded that the disparate effects of obesity and hypertension on total peripheral resistance and intravascular volume counteract and may even offset each other. Thus, obesity may mitigate the effects of chronically elevated total peripheral resistance (and therefore end-organ damage) in essential hypertension. Since both entities affect the heart through different mechanisms, their presence in the same patient results in a double burden to the left ventricle, thereby gently enhancing the long-term risk of congestive failure.     

Effect of simvastatin in patients with type I (insulin-dependent) diabetes mellitus and hypercholesterolemia.

In 10 hypercholesterolemic patients with Type I (insulin-dependent) diabetes, simvastatin 10-40 mg/day was compared to placebo in a randomized, double-blind, cross-over study with treatment periods of 12 weeks. Between each treatment there was a wash-out period of 4 weeks. Compared to placebo, simvastatin reduced total cholesterol by 19% (p less than 0.001) and low density lipoprotein (LDL) cholesterol by 24% (p less than 0.001). Simvastatin therapy reduced plasma triglyceride by 8% and increased high density lipoprotein (HDL) cholesterol by 8%, but neither of these alterations was significant (p greater than 0.05). Diabetic control and daily requirement of insulin were not influenced by simvastatin. In six patients, all men, there were no alterations in the concentrations of dehydroepiandrosterone-sulphate, testosterone, estradiol, prolactin, luteinizing hormone or follicle-stimulating hormone, while sex hormone-binding globulin was significantly (19% (p less than 0.05)) reduced during therapy with simvastatin. Thus, in Type I (insulin-dependent) diabetic patients, simvastatin causes significant reductions in plasma total cholesterol and LDL cholesterol which are similar in magnitude to those observed in non-diabetics. This favourable effect can be obtained without any concomitant negative influence on glucose regulation or total gonadal steroid hormone concentrations.     

Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations

Fasting and postprandial plasma concentrations of glucose, FFA, insulin, glucagon, and GH concentrations were determined in 10 nonobese and 10 obese subjects with normal glucose tolerance. Measurements were made at 0800 h (after a 14-h fast) and at hourly intervals from then until 1600 h. During this time period all individuals ate breakfast at 0800 h (20% of total daily calories) and lunch (40% of total daily calories). Although plasma glucose concentrations were similar throughout the 8-h period in the 2 groups, plasma insulin concentrations were significantly (P less than 0.001) higher in the obese individuals. However, despite the presence of hyperinsulinemia, the obese group also had higher (P less than 0.001) plasma FFA concentration throughout the day. On the other hand, both the absolute and the relative declines in plasma FFA concentration after meals were similar in the 2 groups. Since plasma glucagon and GH concentrations were similar in the 2 groups, altered production of these lipolytic hormones was not responsible for the elevated plasma FFA levels in the obese individuals. These data document the presence in obese individuals of a disassociation in their ability to maintain normal plasma glucose as opposed to plasma FFA homeostasis, and indicate that the increase in plasma FFA concentrations in obesity occurs in the presence of hyperinsulinemia and is not related to abnormalities of either glucagon or GH secretion.