Vitamin D levels and insulin resistance in children born with severe growth restriction.

This study was designed to examine differences in serum 25(OH)D levels between small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) prepubertal children in correlation with birth weight and indices of insulin resistance and ß-cell function. Sixty-five nonobese children were examined at age 5-7.5 years; 27 born SGA and 38 matched AGA. Body weight, height, BMI, and waist circumference were recorded and fasting serum levels of glucose, insulin, 25(OH)D, and parathyroid hormone (PTH) were measured. The homeostasis model assessment for insulin resistance (HOMA-IR) and the ß-cell function index (HOMA-ß%) were estimated. The mean level of 25(OH)D was higher in the SGA group (26.2±10 vs. 17.2±7 ng/ml, p<0.01) but that of PTH was no different. The insulin resistance and ß-cell function indices were higher in the SGA group: HOMA-IR 1.34±0.67 vs. 0.99±0.53, and HOMA-ß% 135±56 vs. 97±60 in the SGA and AGA groups, respectively. In the SGA group, 25(OH)D was correlated with HOMA-ß% but not with HOMA-IR or insulin. In multiple regression, in the total cohort 25(OH)D and HOMA-IR were independently negatively correlated with birth weight (ß= - 0.31, ß= - 0.36, p<0.05) respectively. In conclusion, at prepuberty severely in utero growth restricted children have increased birth weight dependent levels of 25(OH)D, which might exert a regulatory role on ß-cell function.

Effect of rosuvastatin monotherapy or in combination with fenofibrate or ω-3 fatty acids on lipoprotein subfraction profile in patients with mixed dyslipidaemia and metabolic syndrome.

BACKGROUND: Raised triglycerides (TG), decreased high-density lipoprotein cholesterol (HDL-C) levels and a predominance of small dense low density lipoproteins (sdLDL) are characteristics of the metabolic syndrome (MetS). OBJECTIVE: To compare the effect of high-dose rosuvastatin monotherapy with moderate dosing combined with fenofibrate or ω-3 fatty acids on the lipoprotein subfraction profile in patients with mixed dyslipidaemia and MetS. METHODS: We previously randomised patients with low-density lipoprotein cholesterol (LDL-C) > 160 and TG > 200 mg/dl to rosuvastatin monotherapy 40 mg/day (R group, n = 30) or rosuvastatin 10 mg/day combined with fenofibrate 200 mg/day (RF group, n = 30) or ω-3 fatty acids 2 g/day (Rω group, n = 30). In the present study, only patients with MetS were included (24, 23 and 24 in the R, RF and Rω groups respectively). At baseline and after 12 weeks of treatment, the lipoprotein subfraction profile was determined by polyacrylamide 3% gel electrophoresis. RESULTS: The mean LDL size was significantly increased in all groups. This change was more prominent with RF than with other treatments in parallel with its greater hypotriglyceridemic capacity (p < 0.05 compared with R and Rω). A decrease in insulin resistance by RF was also noted. Only RF significantly raised HDL-C levels (by 7.7%, p < 0.05) by increasing the cholesterol of small HDL particles. The cholesterol of larger HDL subclasses was significantly increased by R and Rω. CONCLUSIONS: All regimens increased mean LDL size; RF was the most effective. A differential effect of treatments was noted on the HDL subfraction profile.

Visfatin levels in prepubertal children born small or large for gestational age.

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.

The effects of ezetimibe and/or orlistat on triglyceride-rich lipoprotein metabolism in obese hypercholesterolemic patients.

We investigated the factors influencing triglycerides (TG) reduction during ezetimibe, alone or combined with orlistat, administration. Eighty-six obese hypercholesterolemic subjects were prescribed a low-fat diet and were randomized to ezetimibe (E group), orlistat (O group), or both (OE group) for 6 months. Plasma TG and apolipoprotein (apo) C-III reduction was significantly greater in the combination group compared with monotherapy. Multivariate analysis showed that in E group apoC-III reduction and baseline TG levels were independently positively correlated, whereas baseline apoC-II levels were negatively correlated, with TG lowering. In OE group apoC-III reduction was the only independent contributor to TG reduction.

Lipid profile in subclinical hypothyroidism: is L-thyroxine substitution beneficial?

OBJECTIVE: The significance of dyslipidemia in subclinical hypothyroidism (SH) and the effect of thyroid substitution on lipids remain controversial. The present study aimed to assess the association of SH with lipid abnormalities and to quantify the effect of L-thyroxine therapy on serum lipid profiles. DESIGN: Serum lipid parameters of 66 patients with SH and 75 age- and sex-matched euthyroid controls were evaluated in a cross-sectional study. RESULTS: Patients with SH had higher total cholesterol (TC) (222+/-45 (s.d.) vs 190+/- 32 mg/dl), low-density lipoprotein cholesterol (LDL-C) (139+/-28 vs 118+/-39 mg/dl), apolipoprotein B (149+/-21 vs 139+/-18 mg/dl) and lipoprotein (a) (Lp(a)) (median 12.5 (0.8-101) mg/dl vs 7 (0.8-44) mg/dl) levels compared with euthyroid controls (P<0.05 for all comparisons). In a follow-up study including 37 patients with SH, all measurements were repeated after restoration of a euthyroid state with incremental doses of l-thyroxine. No significant changes in serum lipid profiles were observed except for a decrease in high-density lipoprotein cholesterol (59+/-15 to 55+/-14 mg/dl, P<0.05). However, patients with high pre-treatment TC (> or =240 mg/dl) showed a significant reduction in both TC (278+/-28 vs 257+/-36 mg/dl, P<0.05) and LDL-C (192+/-23 vs 173+/-28 mg/dl, P<0.01) levels. Similar but more pronounced changes were observed in a subgroup of patients with pre-treatment levels of TSH > or =10 microU/ml. Thyroid autoimmunity had no effect on either the baseline or the post-treatment lipid profile. CONCLUSION: Although patients with subclinical hypothyroidism exhibit increased levels of the atherogenic parameters (mainly LDL-C and Lp(a)), thyroid substitution therapy does not seem to significantly improve dyslipidemia in the whole group of patients.

Effect of letrozole on the lipid profile in postmenopausal women with breast cancer.

Hormonal therapy plays a central role in the overall treatment of breast cancer. Aromatase inhibitors can inhibit the aromatase enzyme system resulting in a reduction of oestrogens. Letrozole is a non-steroidal aromatase inhibitor that effectively blocks aromatase activity without interfering with adrenal steroid biosynthesis. The drug can significantly reduce the levels of plasma oestrogens, which remain suppressed throughout the treatment. Data are scarce concerning the influence of these drugs on serum lipid levels. In the present study, we evaluated the effects of letrozole on the serum lipid profile in postmenopausal women with breast cancer. A total of 20 patients with breast cancer were treated with letrozole, 2.5 mg once daily. After an overnight fast, serum lipid parameters (total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides, apolipoproteins A1, B and E and lipoprotein (a)) were measured before treatment and at 8 and 16 weeks afterwards. A significant increase in total cholesterol (P=0.05), LDL cholesterol (P<0.01) and apolipoprotein B levels (P=0.05) in the serum, as well as in the atherogenic risk ratios total cholesterol/HDL cholesterol (P<0.005) and LDL cholesterol/HDL cholesterol (P<0.005) was noticed after letrozole treatment. We conclude that letrozole administration in postmenopausal women with breast cancer has an unfavourable effect on the serum lipid profile.

The effect of atorvastatin on serum lipids, lipoprotein(a) and plasma fibrinogen levels in primary dyslipidaemia--a pilot study involving serial sampling.

We conducted an open-label study to test the effects of atorvastatin on serum lipids, lipoprotein(a) [Lp(a)] and plasma fibrinogen levels. A total of 90 dyslipidaemic, non-smoking patients (45 patients with primary hypercholesterolaemia and 45 patients with primary mixed hyperlipidaemia) aged 48 +/- 11 years were studied. The patients were treated with 20 mg of atorvastatin for 24 weeks, in a single nocturnal dose. At baseline and every eight weeks, the fasting lipid profile, together with serum Lp(a) and plasma fibrinogen levels (Clauss method), were measured. Atorvastatin was highly effective in normalising the serum lipid profile. No significant change in median serum Lp(a) levels was observed in the whole group of patients (0.14 g/l before, vs. 0.16 g/l after, treatment) as well as in patients with raised (> 0.30 g/l) baseline levels (n = 32). A small non-significant increase of plasma fibrinogen was found (3.04 g/l vs. 3.14 g/l) after 24 weeks of atorvastatin administration. The effects of atorvastatin on both these variables did not differ in patients with hypercholesterolaemia or mixed hyperlipidaemia. In conclusion, our findings suggest that the effect of atorvastatin on plasma fibrinogen levels in dyslipidaemic patients without evident vascular disease is not clinically relevant. Furthermore, any rise in fibrinogen levels that may occur is likely to be transient in nature. Further studies are necessary to clarify this issue. There was no evidence that atorvastatin influences serum Lp(a) levels.

Comparison of the efficacy of atorvastatin and micronized fenofibrate in the treatment of mixed hyperlipidemia.

OBJECTIVE: To evaluate and compare the influences of micronized fenofibrate and atorvastatin on serum lipid profile, including lipoprotein(a) levels, and on fibrinogen levels in a large group of patients with primary mixed hyperlipidemia (serum total and low-density lipoprotein cholesterol levels > 240 and 160 mg/dl, respectively, and serum triglyceride level > 200 mg/dl). METHODS: This was a 16-week, open-label, parallel-design study conducted in our lipid clinic. After a 6-week dietary baseline phase, we implemented a treatment phase, during which patients received 10 mg/day atorvastatin (n = 45) or 200 mg/day micronized fenofibrate (n = 46) for 16 weeks. Patients were assigned to one of the drugs in sequential orders. Serum lipid profiles, including levels of lipoprotein(a) and fibrinogen, as well as muscle and liver enzymes, were measured during screening, and during weeks -4, -2, 0, 8, and 16 of the treatment period. RESULTS: Atorvastatin was more effective than was micronized fenofibrate at lowering levels of total and low-density lipoprotein cholesterol, whereas fenofibrate was more effective at lowering levels of triglycerides, and raising levels of high-density lipoprotein cholesterol and apolipoprotein A1. However, micronized fenofibrate could significantly decrease plasma fibrinogen levels, whereas atorvastatin evoked a small increase. CONCLUSION: Both atorvastatin in small doses and micronized fenofibrate are effective for improving serum lipid profiles of patients with mixed hyperlipidemia. However, there are considerable differences between the two drugs concerning their influences on plasma fibrinogen levels.

Lipoprotein (a) levels, apolipoprotein (a) phenotypes and thyroid autoimmunity.

It has been reported that euthyroid normolipidemic males and postmenopausal females exhibit significantly higher serum lipoprotein (a) (Lp(a)) levels compared with age- and sex-matched normolipidemic controls. However, it is well known that there is an inverse correlation between Lp(a) concentration and apolipoprotein (a) (apo(a)) isoform size. Thus, it is imperative to exclude differences in apo(a) isoform frequencies between subjects with or without thyroid autoimmunity in order to verify if there is an association between thyroid autoimmunity and increased Lp(a) concentration. To exclude such an effect of different apo(a) isoform frequencies, we determined apo(a) phenotypes in 22 patients (9 males and 13 postmenopausal females) with thyroid autoimmunity and in 64 (29 males and 35 females) age- and sex-matched individuals without thyroid autoimmunity (control group). There were no significant differences in the values of lipid parameters between the two groups, including Lp(a). We did not detect any significant differences in the apo(a) phenotype frequencies between the two groups. Additionally, in neither of the subgroups formed according to the presence of low molecular vs high molecular weight apo(a) isoforms were there any significant differences in median serum Lp(a) levels between patients with and without thyroid autoimmunity. Thus, our results contradict the previously reported association between thyroid autoimmunity and Lp(a) concentrations.

Lipoprotein (a) concentrations in patients with various dyslipidaemias.

Although the genetic background is the most important determinant of lipoprotein (a) (Lp(a)) concentration other factors, such as coexistent dyslipidaemia, could modify its levels. We undertook the present study to examine the serum Lp(a) concentration in various dyslipidaemias and to reveal any correlation of serum Lp(a) concentration with the other lipid parameters in a large group of dyslipidaemic Greek patients. A total of 242 patients followed as outpatients in our lipid clinic were studied. The patients were stratified into four main groups. Patients with cholesterol levels greater than 5.17 mmol/L but normal triglycerides were regarded as hypercholesterolaemic (n=85), patients with triglycerides greater than 2.25 mmol/L but normal cholesterol levels as hypertriglyceridaemic (n=51), patients with both increased cholesterol and triglyceride levels as having mixed hyperlipidaemia (n=62), and finally patients with decreased (<0.90 mmol/L) high-density lipoprotein (HDL) cholesterol but normal cholesterol and triglyceride levels as having primary hypoalphalipoproteinaemia (n=44). Hypercholesterolaemic patients exhibited the highest serum Lp(a) levels, while hypertriglyceridaemic patients exhibited the lowest. Patients with mixed hyperlipidaemia had intermediate serum Lp(a) concentration, which was significantly higher than that of hypertriglyceridaemic patients but significantly lower than that of hypercholesterolaemic patients. Interestingly, patients with low serum HDL-cholesterol levels presented with low serum Lp(a) concentration similar to that of hypertriglyceridaemic patients. In hypercholesterolaemic patients no correlation was found between serum total and low-density lipoprotein (LDL) cholesterol nor apolipoprotein B (apoB) levels and Lp(a) concentration. On the contrary, in hypertriglyceridaemic patients an inverse correlation was observed between serum triglycerides and Lp(a) concentration. After dividing the hypertriglyceridaemic patients into one group with elevated (>1.3 g/L) serum apoB levels (n=32) and another group with normal apoB levels (n=19), we found that the median serum Lp(a) concentration was three times higher in hyperapoB patients compared to patients with normal apoB levels. We conclude that serum Lp(a) levels are different in various types of primary hyperlipidaemia and are modulated according to the type of lipid elevation.