Catalytic hydrocracking of jatropha oil over natural clay for bio-jet fuel production.

Currently, the conversion of biomass to produce high-valued biofuels such as biodiesel and bio-jet fuel has attached booming interests, when used for partial replacement of petroleum fuels in different ratios is a promising solution due to the problem of depleting petroleum reserves and environmental purposes. Non-edible Jatropha oil can be transformed to biofuel when subjected to were hydrocracking at hydrogen pressure using an activated natural clay as a catalyst in a high pressure batch reactor. The type of product and its quality and quantity depend on the process conditions such as reaction time, temperature, and catalyst type, form, and amount. The present work aims to study the hydrocracking process of Jatropha oil at different operating conditions. The catalyst is characterized using SEM, FTIR, XRF, and XRD. The effect of process conditions variation have been studied and discussed. The results showed the highest yield of 40% bio-jet fuel was achieved at a temperature of 350 °C, H2 pressure of 4 bar, and reaction time of 18 min. the bio-jet fuel products were tested and their specifications were conformed to ASTM D1655 specifications, viz the freezing point (-56 °C), the flash point (53 °C), and existent gum content (5.9 mg/100 ml).

Assessment and referral of patients with short stature by primary care physicians in the Arabian gulf region: Current perspectives from a regional survey.

Children with short stature are frequently referred late to pediatric endocrinologists in the Arabian Gulf region. This is likely a contributing factor to late initiation of treatment despite current evidence suggesting that children with short stature have better outcomes with earlier treatment. This delay in referral could be due to a lack of identification or proper assessment of short stature by front-line physicians. To analyze the assessment and perception of short stature in this group of physicians, an expert group of pediatric endocrinologists developed and disseminated an anonymous online survey of 22 multiple choice questions amongst general pediatricians, pediatric subspecialists, and family medicine physicians in the Arabian Gulf region. Of the 640 respondents, 450 completed the survey (70.3% completion rate). While most surveyed physicians use the correct definition for short stature in children, only 24% reported a consistent use of a wall-mounted stadiometer. Of the respondents, 50% or less would consider referring clinical conditions other than growth hormone (GH) deficiency or idiopathic short stature, 41% would refer a child with short stature as soon as height dropped below the 5th percentile, 57% considered GH a treatment option for short stature, and only 60% consider GH treatment safe. The results of this survey demonstrate knowledge gaps in short stature assessment and referral that need to be addressed through education on short stature amongst target physicians, and lay groundwork for future recommendations to address those gaps in the Arabian Gulf region.

Bovine scavenger receptor class A (SR-A) exhibit specific patterns of regulation in the endometrium during the oestrous cycle and early pregnancy.

In mammals, tight regulation of maternal endometrial function is critical for pregnancy success. In bovine species, endometrial expression of members of the scavenger receptor class A (SR-A) has been listed in high-throughput analyses, but very little is known about the involvement of these immune factors during implantation in mammals. To provide first insights into the contribution of SR-A to endometrial physiology, we analysed the expression and regulation of all members of SR-A (SR-A1, SR-A3-SR-A6) during the oestrous cycle and early pregnancy in cattle. Levels of SR-A1 were increased on Day 20 of pregnancy, whereas SR-A3 levels were increased on Day 13 of the oestrous cycle and of the pregnancy. Although SR-A4 levels were reduced on Day 20 of the oestrous cycle, they remained high in pregnant animals. SR-A5 levels increased by Day 13 of the oestrous cycle and decreased on Day 20, but remained high in pregnant animals. Interferon-τ does not affect SR-A gene expression, whereas progesterone regulates the expression of the SR-A3 and SR-A5 transcripts. Endometrial SR-A3 appeared significantly higher in cows carrying invitro-produced embryos than in AI cows. Our data suggest that members of the SR-A family are involved in endometrial remodelling and regulation of endometrial gland physiology, both processes being critical for implantation in mammals.

Independent positive association of plasma ß-carotene concentrations with adiponectin among non-diabetic obese subjects.

PURPOSE: Many epidemiological studies find an inverse correlation between carotenoids intake or carotenoids plasma concentrations and body mass index (BMI), insulin resistance or metabolic syndrome in the general population. However, it is not clear whether these relationships occur in obese population. METHODS: We conducted a cross-sectional study in 108 obese non-diabetic patients. RESULTS: There was an inverse correlation between plasma levels of pro-vitamin A carotenoids (α-carotene, ß-carotene and ß-cryptoxanthin) and both BMI and insulin resistance (estimated by the HOMA-IR). No correlation between plasma concentrations of lycopene or lutein/zeaxanthin and BMI or insulin resistance was found. The inverse association between the three pro-vitamin A carotenoids and HOMA-IR disappeared after adjustment for BMI and waist circumference. Interestingly, we identified a positive association between concentrations of ß-carotene and adiponectin in plasma that was independent of sex, age, smoking status, BMI and waist circumference. To our knowledge, such association has never been described in obese patients. CONCLUSION: These results suggest the existence of a favourable effect of ß-carotene on insulin sensitivity in obese individuals that could involve a positive regulation of adiponectin, either directly or via its pro-vitamin A activity. The demonstration of the potential benefits of ß-carotene towards insulin sensitivity would open the way to dietary strategies to prevent metabolic syndrome.

SOCS genes expression during physiological and perturbed implantation in bovine endometrium.

In mammals, suppressor of cytokine signalling (CISH, SOCS1 to SOCS7) factors control signalling pathways involved in the regulation of numerous physiological processes including pregnancy. In order to gain new insights into the biological functions of SOCS in the endometrium, a comprehensive analysis of SOCS gene expression was carried out in bovine caruncular (CAR) and intercaruncular (ICAR) tissues collected i) during the oestrous cycle, ii) at the time of maternal recognition of pregnancy and at implantation in inseminated females, iii) following uterine interferon-tau (IFNT) infusion at day 14 post-oestrus, iv) following a period of controlled intravaginal progesterone release and v) following transfer of embryos by somatic-cell nuclear transfer (SCNT). The regulatory effects of IFNT on in vitro cultured epithelial and stromal cells were also examined. Altogether, our data showed that CISH, SOCS4, SOCS5 and SOCS7 mRNA levels were poorly affected during luteolysis and pregnancy. In contrast, SOCS1, SOCS2, SOCS3 and SOCS6 mRNA levels were strongly up-regulated at implantation (day 20 of pregnancy). Experimental in vitro and in vivo models demonstrated that only CISH, SOCS1, SOCS2 and SOCS3 were IFNT-induced genes. Immunohistochemistry showed an intense SOCS3 and SOCS6 staining in the nucleus of luminal and glandular epithelium and of stromal cells of pregnant endometrium. Finally, SOCS3 expression was significantly increased in SCNT pregnancies in keeping with the altered immune function previously reported in this model of compromised implantation. Collectively, our data suggest that spatio-temporal changes in endometrial SOCS gene expression reflect the acquisition of receptivity, maternal recognition of pregnancy and implantation.

Detection of Helicobacter pylori infection in Egyptian patients with chronic calcular cholecystitis.

Reports of Helicobacter pylori in biliary tract diseases in humans are very fragmentary, and therefore there is a need for further investigations. This study aims to detect H. pylori in the bile and gall bladder (GB) of patients with chronic calcular cholecystitis (CCC), and to determine the association of H. pylori infection with gallstone type. Thirty patients with CCC admitted for laparoscopic cholecystectomy were investigated, including upper gastro-endoscopy before cholecystectomy. Rapid urease test and histopathological examination were performed on gastric biopsies. The GB specimens were investigated for the presence of H. pylori by immunohistochemistry (IHC). H. pylori antigen in bile was detected by enzyme immunoassay. Chemical analysis of gallstones was performed to determine type. Immunohistochemistry testing showed 73.3% and 66.7% positivity among GB neck and body biopsies, respectively, demonstrating high sensitivity and specificity. A significant association was found between gastric and GB H. pylori positivity (P < 0.01). H. pylori antigen was detected in bile from three CCC cases. The greatest number of stones were of the calcium bilirubinate type. Gall bladder positivity for H. pylori was accompanied by chronic quiescent gastritis (40.9%). In conclusion, H. pylori infection may be an aetiological factor leading to cholecystitis. Gastric colonisation with H. pylori could be a source for GB infection, and the organism may act as a lithogenic component, especially in the context of pure pigmented gallstones.

Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau.

The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endometria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h (P < 0.05). On day 13 following estrous endometrial expression of nine genes increased [ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven genes decreased (SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, MGC128929, and WBSCR17; P < 0.05) in pregnant compared with cyclic heifers. Of these DEGs, significant differences in expression between pregnant and cyclic endometria were maintained on day 16 for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, and ZSWIM4 (P < 0.05) both their expression was not directly regulated by IFNT in vivo. Analysis of the expression of selected interferon-stimulated genes in blood samples from postpartum dairy cows revealed a significant increase (P < 0.05) in expression of ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared with cyclic controls. In conclusion, RNAseq identified a number of novel pregnancy-associated genes in the endometrium of cattle during early pregnancy that are not regulated by IFNT in vivo. In addition, a number of genes that are directly regulated by short term exposure to IFNT in vivo are differentially expressed on day 18 following estrus detection in the blood of postpartum dairy cows depending on their pregnancy status.

Modulation of maternal immune system during pregnancy in the cow.

There is a molecular crosstalk between the trophoblast and maternal immune cells of bovine endometrium. The uterine cells are able to secrete cytokine/chemokines to either induce a suppressive environment for establishment of the pregnancy or to recruit immune cells to the endometrium to fight infections. Despite morphological differences between women and cows, mechanisms for immune tolerance during pregnancy seem to be conserved. Mechanisms for uterine immunesuppression in the cow include: reduced expression of major histocompatability proteins by the trophoblast; recruitment of macrophages to the pregnant endometrium; and modulation of immune-related genes in response to the presence of the conceptus. Recently, an eGFP transgenic cloned embryo model developed by our group showed that there is modulation of foetal proteins expressed at the site of syncytium formation, suggesting that foetal cell can regulate not only by the secretion of specific factors such as interferon-tau, but also by regulating their own protein expression to avoid excessive maternal recognition by the local immune system. Furthermore, foetal DNA can be detected in the maternal circulation; this may reflect the occurrence of an invasion of trophoblast cells and/or their fragment beyond the uterine basement membrane in the cow. In fact, the newly description of exosome release by the trophoblast cell suggests that could be a new fashion of maternal-foetal communication at the placental barrier. Additionally, recent global transcriptome studies on bovine endometrium suggested that the immune system is aware, from an immunological point of view, of the presence of the foetus in the cow during early pregnancy.

Conceptus-induced changes in the endometrial transcriptome: how soon does the cow know she is pregnant?

This study sought to determine the earliest response of the bovine uterine endometrium to the presence of the conceptus at key developmental stages of early pregnancy. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7, and 13 postestrus, but the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). Of these 514 genes, MX2, BST2, RSAD2, ISG15, OAS1, USP18, IFI44, ISG20, SAMD9, EIF4E, and IFIT2 increased to the greatest extent in pregnant endometria (>8-fold log2 fold change increase). The expression of OXTR, Bt.643 (unofficial symbol), and KCNMA1 was reduced the most, but short-term treatment with recombinant ovine interferon tau (IFNT) in vitro or in vivo did not alter their expression. In vivo intrauterine infusion of IFNT induced the expression of EIF4E, IFIT2, IFI44, ISG20, MX2, RSAD2, SAMD9, and USP18. These results revealed for the first time that changes that occur in the endometrial transcriptome are independent of the presence of a conceptus until pregnancy recognition. The differentially expressed genes (including MX2, BST2, RSAD2, ISG15, OAS1, USP18, IFI44, ISG20, SAMD, and EIF4E) are a consequence of IFNT production by the conceptus. The identified genes represent known and novel early markers of conceptus development and/or return to cyclicity and may be useful to identify the earliest stage at which the endometrial response to the conceptus is detectable.

[The effect of apolipoprotein e polymorphism on plasma cholesteryl ester transfer protein activity in type 2 diabetic patients].

We studied the relationship between apo E polymorphism and cholesteryl ester transfer protein (CETP) activity in 127 type 2 diabetic patients who did not take lipid lowering drugs. Furthermore, we studied the relationship between apo E and CETP in modulating plasma triglyceride and HDL cholesterol. Apo E genotypes were determined by PCR-RFLP and CETP activity was measured using an exogenous way. Our results showed that the CETP activity increased significantly in E2 carrier group compared to E4 carriers and E3E3 homozygous (84.7 +/- 43.9 vs 62.5 +/- 35.9 vs 52.6 +/- 23.6 nmol CE/ml 2h respectively; p = 0.015). However, there was no association between apoE polymorphism and lipid parameter variations. Even after adjustment for CETP activity the results remained unchanged showing that CETP did not step in the relationship between apo E and lipid parameter variations. In conclusion there is an association between apo E polymorphism and CETP activity and this association did not affect the relationship between apo E polymorphism and triglyceride and HDL cholesterol concentrations.

[Thyroid carcinoma and Hashimoto thyroiditis]. / Carcinome de la thyroïde et thyroïdite de Hashimoto.

OBJECTIVES: To study of the association between thyroid carcinoma and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: [corrected] Retrospective study of 78 patients undergoing surgery between 2001 and 2002, with a pathological diagnosis of Hashimoto's thyroiditis. The clinical data and complementary tests performed before surgery are reported. RESULTS: The mean age was 44.6 years, with 77 females and only one male. There were 12 cases of thyroid cancer associated with HT, mostly with the nodular form, with 11 papillary carcinoma (14.1%) and one non-hodgkin B lymphoma of the thyroid. Tumor size varied from 4 to 60 mm with a mean of 26 mm. There was one microcancer (size<10 mm). CONCLUSIONS: We did not find an increased incidence of thyroid cancer associated with this highly selected population of HT patients.

Association between dietary fat and antioxidant status of Tunisian type 2 diabetic patients.

BACKGROUND: The antioxidant enzymes: superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSH-Px) provide a defense against the damage of cells by reactive oxygen species, which increased in diabetic state. It was demonstrated that dietary treatment could improve the antioxidant status in patients with type 2 diabetes mellitus. This study was undertaken to determine if erythrocyte Cu/Zn SOD and GSH-Px activities correlate with dietary nutrients in 35 selected type 2 diabetic patients (21 women and 14 men) without diabetic complications. RESULTS: We found that erythrocyte Cu/Zn SOD was diminished in patients with poor controlled diabetes and GSH-Px activity was significantly decreased in obese compared with non-obese type 2 diabetic patients (1.07+/-0.87 and 2.36+/-1.99 U/ml, respectively; P=0.024). Both erythrocyte Cu/Zn SOD and GSH-Px activities were positively correlated to erythrocyte omega3-polyunsaturated fatty acids (PUFA). In non-obese diabetic patients, only GSH-Px activity was correlated negatively to the fraction of linoleic acid (18:2omega6) and arachidonic acid (20:4omega6) in erythrocytes phospholipids. CONCLUSIONS: The data of this study reveal that activities of erythrocyte antioxidant enzymes were altered in type 2 diabetic patients. Further studies are needed to determine if diet supplemented with omega3-PUFA is required to improve antioxidant defense system in diabetic state.

Modulation of plasma cholesteryl ester transfer protein activity by unsaturated fatty acids in Tunisian type 2 diabetic women.

BACKGROUND AND AIM: Type 2 diabetes mellitus is associated with atherosclerosis, which has been, in part, ascribed to abnormalities in the reverse cholesterol transport system. Among the key actors involved in this pathway is cholesteryl ester transfer protein (CETP) which mediates the transfer of cholesteryl esters (CE) from HDL to apoB-containing lipoproteins. METHODS AND RESULTS: The purpose of this study was to examine CETP activity in 220 patients with type 2 diabetes mellitus (type 2 DM) treated with diet alone or diet and sulphonylurea drugs and to identify the factors that may regulate it in the diabetic state. We also examined the effect of diet on the activity of plasma CETP in a subgroup of type 2 DM women. CETP activity was assessed by measuring plasma-mediated cholesteryl ester transfer (CET) between pooled exogenous HDL and apoB-containing lipoproteins. In 220 patients with type 2 DM, CET was significantly higher in conjunction with higher plasma triglycerides and lower HDL-cholesterol compared to 100 matched healthy controls. Correlation analysis showed that CETP activity was significantly correlated with the HDL-C to apoA1 ratio (r = -0.205, P = 0.003) and to LDL-C to HDL-C ratio in diabetic women (P = 0.010). Furthermore, CETP activity was correlated marginally with total energy intake (P = 0.052) but to a statistically significant extent with the amount of fat consumed daily (P = 0.008). A significant negative correlation was found between plasma CETP activity and MUFA of plasma phospholipids or free PUFA (P = 0.032), especially with omega3-fatty acids (P = 0.001). CONCLUSION: Our findings indicate that CET is accelerated in patients with type 2 DM and that this may be regulated by dietary fatty acids in the diabetic state.

Association of plasma cholesteryl ester transfer protein activity and polymorphism with coronary artery disease extent in Tunisian type II diabetic patients.

INTRODUCTION: Cholesteryl ester transfer protein (CETP), a key protein in reverse cholesterol transport, has a controversial role in atherosclerosis. OBJECTIVES: : We investigated CETP activity and polymorphism in Tunisian type II diabetes and its relationship with coronary artery disease (CAD). DESIGN AND METHODS: 173 type II diabetic patients with or without CAD were compared to 67 controls. RESULTS: The HDL cholesterol concentration was low in a Tunisian population. The B1 allele of the CETP gene was associated with a low concentration of HDL cholesterol and was more frequent in Tunisians than in other populations. In type II diabetic patients, the B1 allele was associated with increased prevalence of CAD only in men (OR=0.357, CI=0.161-0.791, P=0.01). The CETP activity increased in type II diabetic patients compared to controls (P=0.05). Furthermore, the CETP activity was increased in patients with double or triple vessel disease compared to those with single vessel disease (P=0.025). CONCLUSIONS: Our data are in favour of an association between CETP and developing CAD, as well as the extent of CAD.

Lipids and lipoprotein(a) concentrations in Tunisian type 2 diabetic patients; Relationship to glycemic control and coronary heart disease.

The aim of this study was to evaluate plasma lipoprotein(a) [Lp(a)] concentrations in Tunisian patients with type 2 diabetes mellitus (DM), to correlate the values with other lipid parameters, and to examine the relationship to glycemic control and coronary heart disease (CHD). Diabetic patients with and without CHD (n=200) had significantly higher levels of Lp(a) (327.94+/-239.93 mg/l) and a greater proportion of elevated (>300 mg/l) Lp(a) concentrations (46%) compared with 100 healthy nondiabetic controls (269.83+/-225.6 mg/l, P<.01, and 26%, P<.01), while there were no statistically significant difference between diabetics without CHD (n=100) and controls. No significant association of Lp(a) with glycemic control (HbAlc or fasting blood glucose) was noted in diabetic patients. Positive correlations were observed between Lp(a) levels and total cholesterol and LDL-C in all diabetic patients and particularly in diabetic men. Male patients with CHD showed significantly higher plasma Lp(a) levels than those without CHD (P=.023), and 57.3% of patients with CHD showed increase (>300 mg/l) Lp(a) compared with 33.3% of patients without CHD. Elevated levels of Lp (a) and abnormal lipid profile in diabetic men suggest their involvement in atherogenesis and subsequent development of CHD.

[Lipoprotein (a) and ischemic heart diseases in patients with type 2 diabetes]. / Lipoprotéine (a) et cardiopathies ischémiques chez les patients diabétiques de type 2.

Lipoprotein (a) is a new independent coronary risk factor, but the role of lipoprotein (a) in type 2 diabetes remains controversial. The objective of this study was to demonstrate the relationship between the level of lipoprotein (a) and the coronary artery diseases (CAD) in type 2 diabetes. Recruitment was carried out in 3 groups of patients: Group 1: 110 control subjects, Group 2: 115 diabetics (D), Group 3: 105 diabetics with CAD (DC). The mean age was, 51 + 7; 52 + 6; 56 + 6 respectively. Total cholesterol, triglyceride, HDL-C, LDL-C, Apo A-I, Apo B and lipoprotein (a) were measured for the patients. The Lp (a) level was significantly higher in the diabetic groups as compared to the controls (p < 0.05), but this level was different between D and DC: 312 + 232 vs 347.8 + (NS). However, when the Lp (a) level is higher than 300 mg/ml, there is a significant difference between DC and D (53% vs 42% p = 0.05). There is no correlation between Lp level and total cholesterol; however, there is a significant variation of Lp (a) level with LDL-C (r = -0.14, P = 0.01). There is a negative correlation between Lp (a) and HDL-C (r = -0.13, p = 0.03), Lp (a) and ApoA-I (r = - 0.11, p = 0.05); but there is a positive correlation between Lp (a) and ApoB (r = 0.14, p = 0.02). Lp(a) level higher than 300 mg/L constitutes a coronary risk factor in type 2 diabetes. This contributes, with the other lipid disorders, to the increase of the coronary risk factors in diabetes.

Analysis of the postprandial lipid metabolism: use of a 3-point test.

OBJECTIVES: The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required. RESEARCH DESIGN AND METHODS: We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8). RESULTS: The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides). CONCLUSIONS: We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.

Postprandial concentrations and distribution of apo C-III in type 2 diabetic patients. Effect Of bezafibrate treatment.

Apo C-III plays a key role in the metabolism of triglyceride-rich lipoproteins. It has recently been implicated as a potential determinant of the triglyceride (TG) lowering effect of fibrates, which down-regulate its expression. This hypothesis has been explored in ten moderately hypertriglyceridemic (TG 4.50+/-2.40 mmol/l) male type 2 diabetic patients tested with a lipid load before and after 4 weeks of treatment with 400 mg bezafibrate daily. Treatment lowered apo C-III concentrations by 20%, mainly in VLDL. Postprandially, apo C-III was transferred to chylomicrons in proportion to their TG content exclusively from HDL. VLDL retained their apo C-III and the apo C-III:TG ratio decreased as TG contents increased. At the end of the absorptive period (8 h) HDL did not recover the totality of their apo C-III (net loss 19 and 28% respectively before and after treatment, P<0.0001 for time effect). Bezafibrate lowered apo E by 33% (P<0.03). The apo C-III:apo E ratio did not vary significantly under treatment but underwent a postprandial decrease: 13% before and 18% (P=0.01) after treatment. These results indicate that repression of apo C-III expression and lowering of the apo C-III:E ratio are not likely mechanisms for the lipid-lowering effects of fibrates in type 2 diabetic patients. The potent effects on postprandial lipemia are suggestive of an apo C-III-independent stimulation of lipolysis.

Postprandial reverse cholesterol transport in type 2 diabetic patients: effect of a lipid lowering treatment.

Deterioration of reverse cholesterol transport (RCT), an important anti-atherogenic process, may contribute to the largely unexplained severity of cardiovascular risk in type 2 diabetic patients. Among other relevant metabolic perturbations is the impairment in type 2 patients of the postprandial increase in RCT which, in normal subjects, is associated with the transfer to HDL of PL from lipolyzed chylomicrons. We have explored the possibility that improvement of postprandial lipolysis by bezafibrate might also restore the stimulated level of postprandial RCT. Twelve male patients (HbA1c 7.6 +/- 1.6% triglycerides (TG) 4.5 +/- 2.4 mmol/l) were treated for 4 weeks with 400 mg bezafibrate and compared with seven age-matched controls. Lipoproteins were analyzed over 8 h after a 1000 Kcal fat load (80% lipid), serum mediated cholesterol efflux was evaluated using 3H-cholesterol labelled Fu5AH cells. Fasting efflux was lower in patients (17.9 +/- 3.3 vs 19.9 +/- 3.0 a. units, P < 0.05) and decreased postprandially in most instead of increasing, so that area under the time-curve (AUC) was 23% lower than in controls (140 +/- 23 vs 170 +/- 25 units x h, P < 0.001) The patients' HDL failed to acquire PL and gained TG in proportion to lipemia (r = 0.660, P < 0.001). Bezafibrate restored fasting efflux (19.6 +/- 3.6 units, P < 0.005 vs pretreatment) but not postprandial increase of efflux or HDL-PL. AUC of efflux was however improved to 155 +/- 23 units h (P < 0.02). Postprandial efflux related mainly to HDL-PL in controls and patients before treatment. HDL-TG emerged as a significant negative correlate common to all groups (r = -0.674, P < 0.001 8 h after the meal). Impairment of reverse cholesterol transport in diabetic patients might therefore be due to combined postprandial deficit of PL transfer and excess accumulation of TG in HDL. The significant improvement due to fibrate treatment might thus be related to the reduction of HDL-TG contents associated with the improvement of postprandial hyperlipemia.

Changes in free insulin-like growth factor-1 and leptin concentrations during acute metabolic decompensation in insulin withdrawn patients with type 1 diabetes.

UNLABELLED: To determine the effect of acute insulin withdrawal and its subsequent replacement on components of the insulin-like growth factor (IGF)-1 binding protein system and on circulating leptin levels in patients with type 1 diabetes. Seventeen patients (age 31 yr +/-10) with type 1 diabetes treated with continuous subcutaneous insulin infusion (HbA1c 7.6% +/-1.0) were studied. The protocol consisted of two phases: acute insulin withdrawal of up to 8 h followed by a further 2-h period of insulin replacement. For the first phase the basal insulin infusion was stopped (at 0300 h), and for the second a single dose of either regular human or insulin lispro was given subcutaneously (0.2 U/kg). Plasma insulin, glucose, growth hormone, glucagon, IGF-1, free IGF-1, IGFBP-1, -2, -3 and leptin were measured. RESULTS: After interruption of the basal insulin infusion, plasma free insulin levels fell from 60+/-12.0 pmol/L to 10.8+/-4.2 pmol/L, and plasma glucose rose from 5.6+/-0.4 mmol/L to 14.8+/-1.2 mmol/L (P< 0.01). During insulin withdrawal, IGFBP-1 increased by more than 6-fold (from 32+/-8 to 205+/-17 ng/mL, P<0.001), IGFBP-3 increased significantly (from 2631+/-118 to 3053+/-101 ng/mL, P<0.001), and total IGF-1 levels declined modestly (from 226+/-33 to 182+/-26 ng/mL, P<0.001). In contrast, free IGF-1 concentrations (0.72+/-0.22 ng/mL at baseline) were markedly suppressed during insulin withdrawal to values below the detection limit of the assay (0.08 ng/mL) in 15 of the 17 patients (P<0.001). Circulating plasma leptin declined markedly in females from 20+/-3 ng/mL to 11+/-2 ng/mL (P<0.0001) and in males from 10+/-2 ng/mL to 7+/-2 ng/mL (P<0.02). Within 2 h of insulin replacement, the changes in circulating concentrations of IGFBP-1 and IGFBP-3 were partially reversed, and free IGF-1 levels rebounded to 0.54+/-0.22 ng/mL (P<0.1 vs. insulin withdrawal). Growth hormone, glucagon, and IGFBP-2 levels did not change significantly throughout the study. Despite the rapid restoration of plasma insulin and substrate levels, circulating leptin levels continued to fall in the 2-h period after insulin replacement in both females and males. The marked reduction in circulating free IGF-1 after insulin withdrawal and its increase after insulin administration suggest that acute changes in IGFBP concentrations induced by insulin are important regulators of IGF-1 bioavailability in patients with type 1 diabetes. In both males and females, the rapid induction of severe insulin deficiency is associated with a consistent fall in plasma leptin levels.