Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects

OBJECTIVE: To determine whether plasma homocysteine (tHcy) levels were related to insulin resistance and obesity in subjects without diabetes or vascular disease. RESEARCH DESIGN AND METHODS: We studied correlates of plasma tHcy in 26 subjects covering a wide spectrum of obesity and insulin sensitivity (S(I)). The measurement of in vivo insulin sensitivity was performed using the minimal model analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT). RESULTS: There was no relationship between tHcy and body mass index. There was a significant relationship between plasma tHcy and S(I) (r=0.53, P=0.006), demonstrating that the more insulin sensitive subjects had higher levels of tHcy. On log transformation of the plasma insulin values, log insulin correlated negatively with plasma tHcy (r=-0.47; P=0.02). None of the subjects were deficient in vitamin B(12) and folate. Plasma vitamin B(12) was significantly related to plasma tHcy (r=-0.44, P=0.017), although we found no significant relationship between plasma folate and tHcy (r=-0.21, P=0.27). S(I) correlated significantly with vitamin B(12) (r=0.4, P=0.045) whereas, we found no significant relationship between S(I) and plasma folate (r=0.27, P=0.2). On multiple linear regression using tHcy as the dependent variable, S(I) and vitamin B(12) remained significant predictors of plasma tHcy, whereas, age and plasma folate were not predictors of tHcy. CONCLUSIONS: We conclude that in vitamin replete lean and obese individuals, insulin sensitivity correlates significantly with plasma tHcy. This relationship may need to be considered when evaluating the role of plasma homocysteine as a risk factor in patients with obesity and type 2 diabetes.     

Elevated plasma homocysteine concentrations six months after gastroplasty in morbidly obese subjects

OBJECTIVE: To investigate whether the increased homocysteine levels occur in the first 6 months postoperatively, when nutritional intake is the most inadequate and weight reduction is the most drastic. PATIENTS AND METHODS: Fasting glucose, insulin, lipoprotein, homocysteine, folic acid and vitamin B12 levels and oral glucose, tolerance test (OGTT) were determined in 12 morbidly obese subjects (3 men and 9 women with a mean age of 31+/-3 years, mean+/-SEM) before, 6 and 12 months after banded gastroplasty. RESULTS: Gastroplasty resulted in significant weight loss, from 120+/-6 to 92+/-6 and 88+/-7 kgs, 6 and 12 months postoperatively (all p<0.001). Fasting plasma insulin and triglyceride concentrations, the ratio of total cholesterol to HDL cholesterol, glucose and insulin responses to OGTT, and the degree of insulin resistance as expressed by the Homeostasis model index decreased significantly (p<0.05-0.001) following gastroplasty. Fasting plasma homocysteine concentrations increased from 10.2+/-0.8 to 12.1+/-0.6 at 6 months (p=0.036) and 12.0+/-1.2 micromol/l at 12 months (p=0.040), respectively. Pooled plasma homocysteine levels were negatively correlated with serum folate concentrations (r=-0.42, p=0.013). However, serum folate and vitamin B12 levels did not change after gastroplasty, nor did the relation between the loss of body weight and increase in homocysteine levels. CONCLUSION: We observed that elevated circulating homocysteine levels occurred as early as 6 months after gastroplasty despite improvement in carbohydrate and lipoprotein metabolism in morbidly obese Chinese subjects.     

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study

Aims/hypothesis Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B₁₂, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. Methods In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B₁₂, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. Results Two-thirds of mothers had low vitamin B₁₂ (<150 pmol/l), 90% had high MMA (>0.26 μmol/l) and 30% had raised tHcy concentrations (>10 μmol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B₁₂ (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B₁₂ concentrations were the most insulin resistant. Conclusions/interpretation Low maternal vitamin B₁₂ and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Fuel metabolism in anorexia nervosa and simple obesity

To examine insulin sensitivity and the relative contribution of different fuels to energy metabolism in anorexia nervosa and obesity, we measured oxidation (indirect calorimetry) of glucose, lipids, and proteins in the basal state and during an insulin clamp (+45 mU/m2.min) in 11 women with anorexia nervosa (age, 25 +/- 3 years; body mass index [BMI], 13.6 +/- 0.4 kg/m2; fat mass, 15.7% +/- 1.6%), eight obese women (age, 31 +/- 3; BMI 36.0 +/- 1.5; fat mass, 47.1% +/- 1.9%), and eight controls (age, 26 +/- 3; BMI, 21.8 +/- 0.9; fat mass, 25.7% +/- 3.6%). Expressed per lean body mass, (LBM), glucose disposal was equally reduced in anorectics (7.53 +/- 0.62 mg/kg LBM.min) and obese (6.80 +/- 1.07 mg/kg LBM.min) compared with controls (10.64 +/- 0.69 mg/kg LBM.min; P less than .01). The reduction in glucose disposal in anorectics was primarily due to a significant (P less than .01) reduction in glucose storage, while glucose oxidation was normal. In obese women, both storage and oxidation of glucose were reduced compared with controls (P less than .01). Basal energy expenditure was similar in anorectic, obese, and control subjects (20.6 +/- 1.00, 23.7 +/- 0.56, 23.2 +/- 1.36 cal/kg LBM.min, respectively). However, the contribution of glucose, lipids, and proteins to basal energy expenditure differed between anorectic (62%, 16%, 22%), obese (26%, 58%, 16%), and control (30%, 54%, 16%) subjects (P less than .05 v all). In conclusion, in anorexia nervosa, insulin stimulates glucose oxidation more than storage. In obesity, both components of insulin-stimulated glucose metabolism are impaired.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.

OBJECTIVE: To investigate homocysteine levels and their relationship with serum folate and vitamin B12 concentrations with weight loss after the Lap-Band form of gastric restrictive surgery, with the view to minimizing risk. METHODS: We measured levels of fasting plasma homocysteine (tHcy), folate (serum and RBC) and vitamin B12 in two groups. The study group was 293 consecutive patients at 12 (n=192) or 24 (n=101) months review after surgery. The controls were 244 consecutive patients presenting for this surgery. RESULTS: The group losing weight had higher geometric mean tHcy levels: 10.4 (95% CI, 9.8-10.8) micromol/l compared with 9.2 (95% CI, 8.9-9.7) in controls (P<0.001). This occurred with higher folate levels and unchanged vitamin B12 levels. Levels of folate and B12 together explained 35% (r (2)) of the homocysteine variance in the weight loss group compared with only 9% (r (2)) in controls (P<0.001). Those taking regular multivitamin supplements had lower tHcy levels: 9.6 (9.1-10.0) micromol/l vs 12.3 (11.4-13.3) in those not taking supplements (P<0.001). A low normal plateau of tHcy levels occurred at levels of folate >15 ng/l and B12)600 ng/ml. A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group. CONCLUSION: This study shows elevated tHcy levels with weight loss, without lower serum folate or vitamin B(12) levels. There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels. Patients losing weight have significant health benefits; however, they may be at greater risk of vascular events or fetal abnormality in association with raised tHcy levels. Multivitamin supplementation is effective in lowering tHcy levels.     

Plasma total homocysteine level and its association with carotid intima-media thickness in obesity

BACKGROUND: Elevated plasma concentrations of total homocysteine (tHcy) and obesity are risk factors for cardiovascular disease. The relationship between hyperhomocysteinemia and obesity has not been totally elucidated. OBJECTIVE: The first aim of the study was to investigate whether anthropometric measurements and insulin resistance contribute to the variation in homocysteine levels in obese adults. Our second aim was to determine if any relationship exists between the carotid intima-media thickness (IMT) and plasma tHcy levels in obese subjects without traditional cardiovascular risk factors. MATERIAL AND METHODS: Fifty-five obese (15 male, 40 female) and 30 (11 male, 19 female) age- and sex-matched apparently healthy volunteers were included. Exclusion criteria were smoking, hypertension, diabetes, vitamin ingestion, hyperlipidemia, renal failure, liver disease, pregnancy, menopause and secondary obesity such as Cushing's syndrome, hypothyroidism. tHcy, folate, vitamin B12 levels, fasting insulin, glucose, total cholesterol, triglycerides, HDL, LDL particles, uric acid, creatinine and creatinine clearance were measured. Non-invasive ultrasound measurements of carotid IMT were performed. RESULTS: tHcy levels and carotid IMT were comparable between obese and non-obese subjects. Waist/hip ratio (WHR) was related to tHcy and carotid IMT. Hyperhomocysteinemic subjects (tHcy >19.2 micromol/l) had greater WHR than normo-homocysteinemic subjects. Both tHcy levels and carotid IMT were higher in male subjects both in obese and non-obese subjects. No association was observed between insulin resistance and tHcy and carotid IMT. Renal function and abdominal obesity were significant predictors of plasma tHcy levels. CONCLUSIONS: We concluded that, in obese subjects who are free from atherosclerosis and impaired renal function, plasma tHcy levels do not differ from healthy subjects. Plasma tHcy concentrations are not related to carotid IMT in obese subjects during the non-atherogenic stage. Although no significant difference was observed between insulin-resistant and insulin-sensitive subjects compared to the plasma tHcy levels, the relationship between tHcy levels and some components of the insulin resistance syndrome may support the opinion that tHcy may be considered a component of the insulin resistance syndrome.     

Importance of plasma leptin in predicting future weight gain in obese children: a two-and-a-half-year longitudinal study

OBJECTIVE: To determine whether relatively low leptin levels predict changes in adiposity in prepubertal and pubertal obese children. RESEARCH METHODS AND PROCEDURES: In a biracial cohort of 68 obese children (33 male and 35 female; 46 Caucasians and 22 African-Americans, age range 7-18 y), we measured at baseline fasting insulin and leptin levels, height and weight and calculated body mass index (kg/m(2)) and expressed body mass index as (BMI) Z-score. After a 2.5-y follow-up, anthropometric measurements were repeated and changes in weight gain were calculated as changes in BMI Z-score. RESULTS: At baseline obese preadolescent boys and girls had similar age and BMI Z-score, fasting insulin and leptin levels. After an average follow-up of 2.5 y, mean weight change calculated by changes in BMI Z-score from baseline was similar in both groups. In obese adolescent boys and girls at baseline, no significant gender differences were observed for BMI Z-score and insulin levels. In contrast, plasma leptin levels were significantly higher in obese girls compared with obese adolescent boys. At follow-up, there was no significant difference in change in BMI Z-score between obese boys and girls. Multiple linear regression analysis revealed that high basal leptin levels were positively associated with greater changes in BMI Z-score only in girls (r(2)=0.18, P<0.02), after adjusting for basal BMI Z-score, Tanner stage, years of follow-up and basal insulin. High basal leptin levels in girls explained 18% of the weight gain. CONCLUSION: High leptin levels are associated with excessive future weight gain only in girls.     

Physical training decreases total plasma homocysteine and cysteine in middle-aged subjects

AIMS: The aim of this study was to evaluate whether endurance exercise in middle-aged men induces changes in plasma total homocysteine (tHcy) and total cysteine (tCys), and whether these changes depend on the diet especially on vitamin B(6), folic acid and vitamin B(12) intakes. METHODS: Twelve trained subjects (52.33 +/- 2.4 years) and twelve untrained subjects (56.23 +/- 0.9 years) volunteered for the present study. tHcy and tCys were measured with high-pressure liquid chromatography at rest in both groups and during an incremental exercise performed on a cycle ergometer until exhaustion in the trained subjects. RESULTS: At baseline homocysteinemia and cysteinemia were lower in trained subjects (7.48 +/- 0.4 and 183.45 +/- 13.6 micromol/l) compared with untrained subjects (9.79 +/- 0.4 micromol/l, p < 0.001; 229.01 +/-14.7 micromol/l, p < 0.05, respectively). Incremental exercise also induced a decrease in tHcy and tCys concentrations. Moreover, tHcy concentration was negatively related to the folic acid and B(12) intakes in untrained (r = -0.589, p < 0.05; r = -0.580, p < 0.05, respectively) as well as in trained groups (r = -0.709, p < 0.01; r = -0.731, p < 0.01, respectively) whereas no correlation between tCys and vitamin in the diet was observed. CONCLUSION: This study demonstrates that the combined effects of a chronic physical exercise and a high folate and vitamin B(12) intake could be responsible for the reduction of plasma tHcy and tCys concentrations that might be a key for the prevention of many diseases.     

Relation of plasma leptin to lipoproteins in overweight children undergoing weight reduction

BACKGROUND: In obese children, plasma leptin is elevated and correlates with the body mass index (BMI). In obese adults, plasma leptin decreases during weight reduction. Since the leptin system changes dynamically in puberty, we asked whether weight reduction in obese adolescents has similar consequences for plasma leptin as in overweight adults. In plasma, a portion of leptin is bound to several as yet uncharacterised proteins. We therefore studied the possible association of leptin with plasma lipoproteins. SUBJECTS AND METHODS: We measured plasma leptin, lipoprotein cholesterol and apolipoproteins (apo) A-I and B in 34 obese children (age 12.5+/-1.9 y, relative BMI 165.0+/-28.1%) before and after three weeks of weight reduction in a dietary camp. Lipoprotein binding of endogenous and exogenously radiolabelled leptin was studied by preparative ultracentrifugation. RESULTS: Plasma leptin was higher in obese children than in normal weight controls and fell from 16.5+/-9.8 ng/ml to 10.0+/-8.6 ng/ml after weight reduction (P < 0.001). In multivariate regression, relative BMI and apoA-I were significant predictors of baseline leptin and accounted for 38% (P = 0.003) and 15% (P = 0.006) of the variance of baseline leptin concentrations in obese children. Only the difference in plasma high-density lipoprotein (HDL)-cholesterol independently predicted the change of plasma leptin that was associated with weight reduction, explaining 29% of the variance of leptin changes (P = 0.0032). A substantial portion of both endogenous and exogenously labelled leptin was recovered with HDL isolated by ultracentrifugation. CONCLUSIONS: We conclude that plasma leptin decreases in overweight children undergoing short term weight reduction. In obese children, plasma apoA-I and HDL-cholesterol are independent predictors of leptin concentrations during weight loss, respectively. In addition, HDLs transport a variable portion of leptin in the circulation.     

Folate, vitamin B₁₂ and total homocysteine levels in Arab adolescent subjects: reference ranges and potential determinants

Background &; AimsElevated circulating fasting total homocysteine (tHcy) concentration is associated with an increased risk of occlusive vascular disease in adults. Important determinants of tHcy levels are folate, vitamin B₁₂ and vitamin B₆. This study aimed to investigate age, gender, and body mass as determinants of folate, vitamin B₁₂ and tHcy levels in Arab older children and adolescents and to propose population, gender and age-specific reference ranges for these biomarkers.Methods &; Results774 (316 boys, 458 girls) healthy 10–19 yr olds attending secondary schools in Kuwait were assessed for anthropometry and fasting blood levels of Hcy, folate and vitamin B_12. The mean (95% CI) serum levels of tHcy, folate and vitamin B₁₂ were respectively 6.57 μmol/L (6.42–6.73), 16.0 ng/ml (15.6–16.3) and 354.3 pg/ml (343.0–365.7). Boys had significantly higher tHcy and folate concentrations than the girls, although vitamin B₁₂ levels were greater in the latter. Folate and vitamin B₁₂ levels decreased significantly with age, while correspondingly, tHcy levels increased, with mean values (μmol/L) for boys (6.71; 8.25) and girls (5.36; 6.67) aged 10–14 yr and 14–19 yr respectively. Bivariate and multivariate analyses with adjustment for confounders such as age, gender, need for dietary control and socio-demographic variables indicated that the independent determinants of levels of tHcy were age, gender and body mass.ConclusionThere is an age-related increase in tHcy in adolescents reflecting decreased levels of folate and vitamin B₁₂, with the suggestion that age-related reference ranges for these biomarkers be used. These observations may have implications for prevention of future atherogenic disease.     

Ghrelin secretion in severely obese subjects before and after a 3-week integrated body mass reduction program

Ghrelin, the endogenous ligand of GH-secretagogue receptors, has been implicated in the regulation of feeding behavior and energy balance. Aim of the study was to investigate ghrelin levels in fasting conditions and after a standard meal test in obese subjects before and after a 3-week integrated body weight reduction (BWR) program (consisting of energy-restricted diet, exercise training, psychological counselling and nutritional education). Weight, height, fat mass, fat free mass (by impedentiometry), circulating ghrelin, insulin and leptin levels were evaluated in 10 obese subjects (3 male, 7 female; mean age: 35 +/- 9.3 yr; body mass index BMI: 45.2 +/- 10.6 kg/m2) before and after weight reduction. At baseline, obese subjects showed significantly lower ghrelin levels than controls, which were negatively correlated with BMI, weight, insulin and leptin levels. Fasting ghrelin levels were not modified by standard meal test in obese subjects (from 110.8 +/- 69.7 to 91.8 +/- 70.2 pmol/l p=ns), while a significant reduction was observed in controls (from 352.4 +/- 176.7 to 199.0 +/- 105.2 pmol/l; p<0.01). After a 3-week integrated BWR program obese subjects significantly reduced weight, BMI and leptin levels, while no significant changes were found both in fasting ghrelin and in ghrelin response after the meal. In conclusion, 5% weight loss obtained after a short-term period of integrated BWR program is not sufficient to normalize fasting ghrelin levels nor to restore the normal ghrelin suppression after a meal in severely obese subjects.     

Relation of plasma total homocysteine, folate and vitamin B12 levels to bone mineral density in Moroccan healthy postmenopausal women

To test whether in Moroccan healthy postmenopausal women, levels of plasma total homocysteine (tHcy), folate, and vitamin B12 are related to BMD. A total of 188 volunteer postmenopausal women were recruited from our blood taking center between April 2008 and December 2008. Each subject completed a standardized questionnaire designed to document putative risk factors of osteoporosis. Bone mineral density was determined by a Lunar Prodigy Vision DXA system, and blood samples for plasma tHcy, folate, vitamin B12, and serum parathyroid hormone (PTH) were taken. Comparison between women with osteoporosis, osteopenia and normal BMD showed that the osteoporotic women were significantly older, had lower weight and height than the women of the other groups. Plasma tHcy was significantly higher in the osteoporotic group. Levels of tHcy were inversely related to BMD at the lumbar spine, at the total hip and plasma vitamin B12 and positively related to age and creatinine. Multiple regression analysis showed that age and BMI were the main predictors of BMD at the lumbar spine, whereas the main predictors of BMD at the total hip were age, BMI, plasma tHcy, and plasma vitamin B₁₂. tHcy and vitamin B12 are independent risk factors for osteoporosis in Moroccan healthy postmenopausal women.     

Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: a pilot study

OBJECTIVE: Our first objective was to compare plasma total homocysteine (tHcy) concentrations in juvenile idiopathic arthritis (JIA) patients requiring methotrexate (MTX) treatment and healthy children. Our second aim was to evaluate the influence of low-dose (10-15 mg/m2/week) MTX treatment combined with folic acid supplementation (1 mg/d) or placebo on tHcy concentrations in JIA patients. METHODS: In 17 JIA patients and 17 age- and sex-matched healthy children, baseline tHcy concentrations were measured. When MTX treatment was initiated, JIA patients were randomly assigned to folic acid 1 mg/d/p.o. followed by placebo (8 weeks each) or vice versa. Blood samples for measurement of tHcy, vitamin B6, B12 and folate were taken after 4 weeks, 12 weeks and 20 weeks of treatment. RESULTS: 1) In the healthy children the mean tHcy concentration was 6.3 +/- 1.68 mumol/l as compared to 9.99 +/- 5.17 mumol/l in JIA patients (p < 0.04). At baseline, 5/17 JIA patients had tHcy concentrations > 10.5 mumol/l, the 99th percentile for teenagers. 3/5 patients even exceeded the upper normal level for adults (tHcy > or = 15 mumol/l). MTX treatment did not result in a significant increase of tHcy and folic acid supplementation had no significant impact on tHcy levels. CONCLUSION: This pilot study shows that patients with JIA requiring MTX treatment have significantly elevated baseline plasma tHcy concentrations compared to age- and sex-matched healthy controls. No significant impact of MTX and folate supplementation on tHcy concentration was found.     

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.     

Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects.

AIMS: The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case-control study. METHODS AND RESULTS: Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n=109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile=1.34, 95% CI 1.01-1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P<0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR=0.69 (95% CI 0.49-0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR=17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein. CONCLUSION: tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.     

Effects of sibutramine in non-dieting obese women

The aim of this study was to evaluate the effects of sibutramine on plasma leptin levels, body weight and glucose metabolism in non-dieting women. Fourteen healthy, non-diabetic, obese women were studied before treatment, after 1 week of placebo administration, and after a 2-week course of sibutramine (10 mg/day). At each of these stages, we assessed body composition, measured the levels of plasma leptin, C-peptide and various biochemical parameters, and also recorded plasma insulin and glucose levels during oral glucose tolerance tests. After 1 week of placebo treatment, there were no significant changes in any of the parameters. However, two weeks of 10 mg/day sibutramine dropped plasma leptin levels from a mean (+/-SE) of 48.84+/-4.54 to 42.84+/-4.74 ng/ml (p<0.04), reduced BMI from 39.36+/-2.01 to 38.57+/-1.93 kg/m2 (p<0.002), and decreased insulin resistance (IR, as measured using the homeostasis model assessment of insulin resistance) from 5.59+/-0.85 to 3.66+/-0.43 (p<0.02). There was no correlation between the reduction in leptin concentration and the decrease in BMI, fat mass, percent body fat, IR, C-peptide, or the area under curve for glucose or insulin. There was also no correlation between the decrease in leptin levels and the increases that occurred in the insulin sensitivity index or the hepatic sensitivity index. The results showed that treatment with 10 mg/day sibutramine significantly reduces BMI, IR and leptin levels in non-dieting obese women.     

Effects of short-term energy restriction and physical training on haemostatic risk factors for coronary heart disease in obese children and adolescents

OBJECTIVE: To study the changes of haemostatic risk factors for coronary heart disease during a weight reduction programme in obese children and adolescents. DESIGN: A short-term longitudinal study. SUBJECTS: Thirty-seven obese white girls (age, 12+/-1.8 y; body mass index (BMI), 26.9+/-5.25) and 19 obese white boys (age, 11.9+/-1.7 y; BMI, 26.2+/-5.2). MEASUREMENTS: Fibrinogen, factor VII coagulant activity, von Willebrand factor antigen, and soluble P-selectin were determined before and after a 3 week programme including energy restriction and physical activities. RESULTS: All determined haemostatic risk factors decreased significantly during the programme. Changes in risk factors were correlated to changes in body composition. Children and adolescents with the highest initial concentrations showed the greatest decreases. CONCLUSION: Energy restriction combined with physical activity improves the haemostatic risk profile in obese children and adolescents.     

Occurrence of hyperhomocysteinemia 1 year after gastroplasty for severe obesity

Severe obesity exposes one to an increased risk of cardiovascular mortality. Gastroplasty has been shown to induce substantial weight loss and to improve the atherogenic profile of severely obese subjects. However, vitamin deficiencies after gastroplasty have been reported. Because hyperhomocysteinemia, an independent risk factor for cardiovascular disease, is influenced by nutritional status (and especially by folate intake), we hypothesized that a marginal folate deficiency induced by gastroplasty could promote hyperhomocysteinemia. Thus, plasma homocysteine concentrations were measured by high-performance liquid chromatography in 53 severely obese patients (body mass index = 42 +/- 1), before and 1 yr after vertical gastroplasty. Plasma homocysteine concentrations increased, on an average, from 9.9 +/- 0.4 to 12.8 +/- 0.6 micromol/L (P < 0.0001). This increase in homocysteine levels was observed in two thirds of the subjects, leading to clear-cut hyperhomocysteinemia (>15 micromol/L) in 32%. The changes in homocysteine concentrations were correlated to weight loss (P < 0.001) and to decrease in plasma folate concentrations (P < 0.01). Whereas gastroplasty induced a mean 32-kg weight loss and a striking improvement in conventional risk factors, the occurrence of iatrogenic hyperhomocysteinemia might hamper the benefit of surgery on cardiovascular risk in most of the patients. Our results further support use of a systematic efficient folate supplementation after gastroplasty.     

Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) have a clustering of cardiovascular risk factors, such as obesity, lipid abnormalities, impaired glucose tolerance, insulin resistance, and hypertension. Exercise is reported to lower the incidence of cardiac events. The effect of exercise on plasma homocysteine concentrations, an independent cardiovascular risk factor, has not been previously reported in women with PCOS. We examined the effects of exercise on plasma total homocysteine concentrations in young overweight or obese PCOS women [age (mean +/- SD), 30.6 +/- 6.6 yr; body mass index, 35.49 +/- 7.57 kg/m(2)]. Twenty-one women consented to a 6-month exercise program; 12 women (exercisers) adhered to the program, whereas 9 (nonexercisers) did not. In both groups of women, the following parameters were recorded at baseline and 6 months: body mass index, waist-to-hip ratio, and aerobic capacity (maximal oxygen consumption); blood samples were taken after an overnight fast for plasma total homocysteine, insulin, and other biochemical parameters. A significant decrease in plasma total homocysteine concentrations (P < 0.001) and waist-to-hip ratio (P = 0.041) and a significant increase in maximal oxygen consumption (P = 0.019) were recorded at 6 months, compared with baseline in the exercise group. This decrease in homocysteine was not explained by changes in anthropometric or biochemical parameters. In contrast, no significant changes in any of the variables were observed in the nonexercise group. Our study has provided the first evidence that regular exercise significantly lowers plasma homocysteine in young overweight or obese women with PCOS, a group at increased risk of premature atherosclerosis. The precise mechanism by which exercise is associated with a reduction in homocysteine remains to be elucidated.     

The effect of a rapid weight loss induced by laparoscopic adjustable gastric banding on arterial stiffness, metabolic and inflammatory parameters in patients with morbid obesity

OBJECTIVE: To determine the effect of drastic weight loss on arterial compliance, inflammatory and metabolic parameters in patients with morbid obesity with and without cardiovascular risk factors who underwent laparoscopic adjustable gastric banding (LAGB). DESIGN: Open prospective study, morbidly obese subjects divided into low- and high-risk group were evaluated before and 4 months after LAGB. SUBJECTS: Forty-one Caucasian subjects aged between 16 and 55 years, with morbid (grade 3) obesity (20 low- risk and 21 high-risk subjects) who underwent LAGB and completed a 16-week follow-up. MEASUREMENTS: Patients were evaluated at baseline and 4 months after LAGB for body mass index (BMI), arterial blood pressure (BP), metabolic factors including lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-C reactive protein (CRP) and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity of large and small arteries was evaluated using pulse-wave contour analysis method (HDI CR 2000, Eagan, Minnesota) at baseline and after 4 months. RESULTS: Body mass index reduction induced by LABG, from 43.55+/-5.11 to 35.10+/-4.87 in low-risk patients and from 42.90+/-3.22 to 35.00+/-3.24 in high-risk patients, significantly improved small artery elasticity (SAE) from 6.30+/-2.74 to 7.25+/-1.85, in morbidly obese patients with multiple cardiovascular risk factors (high-risk group). Improvement in SAE was accompanied by improvement of arterial BP, glucose and lipid metabolism, and reduction of CRP values. CONCLUSION: Although dramatic weight reduction induced by surgical intervention was associated with similar changes in body weight and significant improvement of metabolic and inflammatory parameters in two groups of obese patients, SAE improved only in high-risk patients.