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Objective. The retinol-binding protein 4 (RBP4) has been linked to the insulin resistance state in obesity and type 2 diabetes in animal studies. Data in humans are controversial and their relationship with organ damage in diabetic patients is lacking. We studied the association of plasma RBP4 with organ complications in type 2 diabetic patients. Setting. Sant Joan University Hospital, Reus, Spain. Subjects. 165 nonsmoker type 2 diabetic subjects according to American Diabetes Association criteria, aged 36–79 years, without proteinuria or severely decreased glomerular filtration rates (MDRD-GFR <30 mL min−1 1.73 m−2), were included in the study. Main outcome measure. Plasma RBP4 concentrations were the primary outcome variable. Statistics were performed in relation to clinical and subclinical arteriosclerosis, renal function parameters and biochemical data. Results. Plasma RBP4 concentrations were positively correlated with serum creatinine levels ( r = 0.322, P < 0.001) and inversely correlated with MDRD-GFR ( r = −0.468, P = 0.009). Patients with moderately renal dysfunction (MDRD-GFR <60 mL min−1 1.73 m−2) had higher plasma RBP4 concentrations than those with normal to mildly decreased GFR (55.3 ± 24.6 vs. 40.8 ± 15.4, P <0.001). Patients in the top quartile of RBP4 concentrations had an increased adjusted odds ratio for moderately renal dysfunction compared with lower quartiles (4.68; 95% CI: 1.52–14.36, P = 0.007). The presence of microalbuminuria was not associated with RBP4. Plasma RBP4 concentrations were higher in those subjects with previous clinical arteriosclerosis than in event-free subjects (48.8 ± 24.2 vs. 40.6 ± 13.9, P = 0.045). The presence of retinopathy or polyneuropathy did not differ across RBP4 quartiles. Conclusions. Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects. [ABSTRACT FROM AUTHOR]

Background Antiretroviral drug efficacy has been widely studied in relation to viral factors. Mutations in the HIV co-receptors and their natural chemokines, however, may be critical in HIV infection and treatment response. We compared the efficacy of protease inhibitor (PI) treatment among PI-naïve patients grouped according to whether they carried the chemokine CC motif receptor 2 ( CCR-2) 64I and monocyte chemoattractant protein 1 ( MCP-1)–2518G alleles. Methods and results HIV-infected patients who were PI-naive were selected for the study ( n=164) but there was no restriction on lymphocyte CD4 count or plasma HIV viral load. Follow-up was for the first 24 months of treatment. Clinical and laboratory data were obtained every 3 months. All the participants were genotyped for the MCP-1–2518G, CCR-2 64I, CCR-5Δ32 and stromal derived factor 1 ( SDF1) 3′A mutated alleles. The results indicated that patients carrying the mutated allele of MCP-1 had a higher mean CD4 cell count throughout the follow-up period than those with the common allele ( P=0.01). Also, patients with the MCP-1 and CCR-2 mutated alleles were more likely to continue to have an undetectable viral load following treatment ( P=0.05). Conclusion A better response to PI treatment appears to be conferred by mutations in the host MCP-1 and CCR-2 genes, and may be related to the cellular axis-of-entry used by the retrovirus. [ABSTRACT FROM AUTHOR]

Halkes CJM, van Wijk JPH, Ribalta J, Masana L, Castro Cabezas M (University Medical Center, Utrecht, the Netherlands, and University Hospital of Sant Joan, Rovira i Virgili University, Reus, Spain). Diurnal triglyceridaemia and insulin resistance in mildly obese subjects with normal fasting plasma lipids. J Intern Med 2004; 255: 74–81. A novel method has been developed to study diurnal triglyceride (TG) profiles using repeated capillary self-measurements in an ‘out-of-hospital’ situation. We assessed the diurnal capillary TG (TGc) profile in males with mild obesity and evaluated the use of plasma and capillary TG as markers of insulin resistance. Cross-sectional study. Fifty-four lean (body mass index, BMI < 25 kg m−2) and 27 mildly obese (25 < BMI < 30 kg m−2), normolipidaemic males measured capillary TG concentrations on six fixed time-points over a 3-day period in an ‘out-of-hospital’ situation. The total area under the TGc curve (TGc-AUC) and incremental area under the TGc curve (TGc-IAUC) were used as estimation of diurnal triglyceridaemia. Fasting blood samples were obtained once. Food intake was recorded by all participants. Obese and lean subjects had comparable fasting capillary TG concentrations (1.37 ± 0.40 mmol L−1 and 1.32 ± 0.53 mmol L−1, respectively). However, during the day, obese subjects showed a greater TG increase, resulting in significantly higher TGc-AUC (27.1 ± 8.4 and 23.0 ± 6.3 mmol h−1 l−1, respectively; P < 0.05) and TGc-IAUC (7.9 ± 5.8 and 4.6 ± 6.6 mmolh−1 L−1, respectively; P < 0.05). The total group of 81 males was divided into quartiles based on fasting plasma TG, fasting capillary TG, TGc-AUC and TGc-IAUC. Amongst these variables, TGc-AUC was the only significant discriminator of subjects with high homeostasis model assessment (HOMA) (insulin resistance) compared with low HOMA (insulin sensitive). Overall, BMI was the strongest determinant of HOMA. Diurnal TG profiles can be used to investigate postprandial lipaemia in both lean and mildly obese subjects and may help to detect subjects with an underlying disposition for hypertriglyceridaemia related to insulin resistance, i.e. the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background Elevated fasting and postprandial triglycerides (TG) are established risk factors for Coronary Heart Disease (CHD). Usually, fasting plasma TG are measured, although TG are mainly produced in a postprandial state. Our objective was to investigate diurnal TG profiles using serial capillary TG measurements, in normolipidemic healthy males. Materials and Methods Forty-eight, non-obese, non-smoking males (range: 20–55 years, mean age: 32 ± 12 years), measured diurnal capillary TG, at six fixed timepoints during the day on three different days and recorded their food intake. Insulin sensitivity was estimated by HOMA. Diurnal capillary TG profiles were calculated as integrated area under the mean capillary TG curve (TGc-AUC). Results All subjects had normal fasting plasma TG and cholesterol. The average TGc-AUC was 23.6 ± 6.7 mmol h L-1. Significant correlations with TGc-AUC were: fasting insulin (r = 0.40, P < 0.005), HOMA (r = 0.32, P < 0.05), relative fat mass (r = 0.31, P < 0.05), dietary protein-(r = 0.31, P < 0.05) and saturated fat intake (r = 0.30, P < 0.05). Age was not associated to diurnal triglyceridemia. After subdividing the group into quartiles on the base of TGc-AUC, differences were found between the highest (n = 12) and lowest quartile (n = 12) for: fasting capillary TG, fasting insulin, HOMA and systolic blood pressure. Fasting plasma TG and dietary intake were not different. Conclusion Diurnal TG profiles in healthy normolipidemic males are not age-dependent, but are associated to insulin sensitivity, fat mass and diet. Diurnal capillary TG profiles may be a valuable additional tool in estimating a risk profile for CHD since significant differences in diurnal TG are not always reflected by elevated fasting plasma TG. [ABSTRACT FROM AUTHOR]

Six patients (four women and two men) with mild to moderate hypercholesterolemia, but with no clinical evidence of the disease being monogenic familial hypercholesterolaemia and who, over the previous 3 months on a rigidly controlled hypolipidaemic diet therapy, showed no reduction in plasma cholesterol levels, were recruited into a study to assess the metabolic effects of Pirozadil, a new nicotinic acid derivative. After a 3 month treatment period, a significant reduction in plasma cholesterol from 299.8 ± 31.2 mg/dl (mean ± SD) to 256.8 ± 18.1 mg/dl ( P < 0.02) and Low Density Lipoprotein (LDL) cholesterol from 211.7 ± 44.9 mg/dl to 168.8 ± 19.0 mg/dl ( P < 0.05) was observed. Although there was a trend toward decreased plasma and Very Low Density Lipoprotein (VLDL) triglyceride, the differences did not reach statistical significance. High Density Lipoprotein (HDL) cholesterol was unchanged. The drug was well tolerated with no side effects noted. To assess the mode of action, autologous125I-labelled LDL was injected and apoprotein B (apo B) kinetic parameters were measured; production rate (PR) and fractional catabolic rate (FCR). An in vitro measurement of the in vivo catabolism (LDL-apo B receptor activity in freshly isolated lymphocytes) was also measured pre- and post-treatment. The pharmacological intervention resulted in a significant decrease of 19.9% in PR from 10.5 ± 1.81 mg/kg/d to 8.41 ± 1.13 mg/kg/d ( P < 0.05) while the FCR remained relatively unchanged (0.260 ± 0.042 vs 0.248 ± 0.040 pools/d) as did the LDL receptor activity (78.2 ± 20.9 vs 69.3 ± 21.4 ng LDL/mg cell protein/hr). Our data suggest that in polygenic hypercholesterolaemia, a condition in which the LDL receptor and hence catabolism is normal, the alternative therapy to facilitating enhanced catabolism is one that decreases the synthesis of the lipoprotein and, as such, nicotinic acid and its derivatives may be effective hypolipidaemic agents. [ABSTRACT FROM AUTHOR]

Reports on the proposal to redefine familial combined hyperlipidemia (FCHL) made during the May 2001 Scientific Sessions of the European Society for Clinical Investigation. Characteristics of FCHL; Reasons behind the proposal.

Objective: This work studied the presence of inflammatory and atherogenic lipoprotein markers that could explain the high incidence of cardiovascular disease (CVD) reported in rheumatoid arthritis (RA) patients., Methods: Inflammatory markers were 1) soluble adhesion molecules (intercellular adhesion molecule [ICAM] and vascular cell adhesion molecule [VCAM]), 2) C-reactive protein (CRP), 3) fibrinogen (Fb), 4) cytokines (interferon-gamma [IFNgamma], tumor necrosis factor alpha [TNFalpha]), and 5) secretory group IIA phospholipase A2 (sPLA2-IIA). Atherogenic lipoprotein markers were 1) the size distribution of plasma lipoprotein subclasses, and 2) the binding affinity of low-density lipoprotein (LDL) to chondroitin 6-sulfate glycosaminoglycan (GAG)., Results: RA patients (n = 31) and matched controls (n = 28) had similar plasma concentrations of total cholesterol, triglycerides, Apo B, Apo A-I, very low-density lipoprotein, intermediate-density lipoprotein, and high-density lipoprotein (HDL). RA patients had significantly higher plasma levels of sPLA2-IIA, ICAM, CRP, Fb, TNFalpha, and IFNgamma compared with controls. RA patients also had significantly higher levels of small, dense LDL-1 (P < 0.05) and lower levels of small HDL-2 particles (P < 0.001) compared with controls. In addition, LDL from RA patients had a significantly higher binding affinity (Kd) to GAG (mean +/- SD Kd 204+/-22.4 nM Apo B) than did LDL from control subjects (Kd 312+/-36 nM Apo B) (P < 0.05). This Kd value showed a significant negative correlation with the plasma levels of LDL-1 (r = -0.566, P < or = 0.004). In RA patients, a significant positive correlation was obtained between sPLA2-IIA and CRP, ICAM, and LDL-1. HDL-2 showed a negative correlation with sPLA2-IIA., Conclusion: These atherogenic lipoprotein factors combined with the presence of chronic inflammation may contribute to the high CVD-related mortality in RA patients.