GooD4Mum: A general practice-based quality improvement collaborative for diabetes prevention in women with previous gestational diabetes.

AIMS: Gestational diabetes (GDM) and Type 2 diabetes pose tremendous health and economic burdens as worldwide incidence increases. Primary care-based systematic diabetes screening and prevention programs could be effective in women with previous GDM. GooD4Mum aimed to determine whether a Quality Improvement Collaborative (QIC) would improve postpartum diabetes screening and prevention planning in women with previous GDM in general practice. METHODS: Fifteen general practices within Victoria (Australia) participated in a 12-month QIC, consisting of baseline and four quarterly audits, guideline-led workshops and Plan-Do-Study-Act feedback cycles after each audit. The primary outcome measures were the proportion of women on local GDM registers completing a diabetes screening test and a diabetes prevention planning consultation within the previous 15 months. RESULTS: Diabetes screening increased with rates more than doubled from 26% to 61% and postpartum screening increased from 43%-60%. Diabetes prevention planning consultations did not show the same level of increase (0%-10%). The recording of body mass index improved overall (51%-69%) but the number of women with normal body mass index did not. CONCLUSIONS: GooD4Mum supported increased diabetes screening and the monitoring of high risk women with previous GDM in general practice.

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a randomized cross-over study.

BACKGROUND AND AIMS: To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes. METHODS AND RESULTS: Twenty-seven subjects (47-77 yrs) with type 2 diabetes were randomly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet. Most of the meals and staple foods for the intervention diet were provided. Lipids, glycemic variables, blood pressure, homocysteine, C-reactive protein, plasma carotenoids and body composition (anthropometry and dual energy X-ray absorptiometry) were assessed at baseline, and at the end of both diet periods. Dietary adherence was monitored using plasma carotenoid and fatty acid (FA) analysis, complemented by diet diaries. Compared with usual diet, on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1% (95% CI: 6.5-7.7) to 6.8% (95% CI: 6.3-7.3) (p=0.012) and diet quality improved significantly [plant:animal (g/day) food ratio increased from 1.3 (95% CI: 1.1-1.5) to 5.4 (95% CI: 4.3-6.6) (p<0.001)], plasma lycopene and lutein/zeaxanthin increased (36% and 25%, respectively), plasma saturated and trans FAs decreased, and monounsaturated FAs increased. CONCLUSION: A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes, without adverse effects on weight.

Ability of traditional lipid ratios and apolipoprotein ratios to predict cardiovascular risk in people with type 2 diabetes.

AIMS/HYPOTHESIS: The apolipoprotein B (ApoB):apolipoprotein A (ApoA)-I ratio may be a better indicator of cardiovascular disease (CVD) risk in people with type 2 diabetes than traditional lipid risk markers (LDL-cholesterol, HDL-cholesterol and triacylglycerol), but whether the ApoB:ApoA-I ratio should be used to indicate lipid-lowering therapy is still debated. METHODS: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study randomised 9,795 patients with type 2 diabetes to fenofibrate (200 mg daily) or placebo and followed them up for a median of 5 years. We compared ApoB, ApoA-I, ApoAII and the ApoB:ApoA-I ratio with traditional lipid variables as predictors of CVD risk. We estimated the HR of the effect of 1 SD difference in baseline concentrations of lipids, apolipoproteins and respective ratios on the risk of CVD events and also used receiver operating characteristic curve analysis. RESULTS: In the placebo group, the variables best predicting CVD events were non-HDL-cholesterol:HDL-cholesterol, total cholesterol:HDL-cholesterol (HR 1.21, p < 0.001 for both), ApoB:ApoA-I (HR 1.20, p < 0.001), LDL-cholesterol:HDL-cholesterol (HR 1.17, p < 0.001), HDL-cholesterol (HR 0.84, p < 0.001) and ApoA-I (HR 0.85, p < 0.001). In the fenofibrate group, the first four predictors were very similar (but ApoB:ApoA-I was fourth), followed by non-HDL-cholesterol and ApoB. Lipid ratios and ApoB:ApoA-I performed better than any single lipid or apolipoprotein in predicting CVD risk. CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes in the FIELD study, traditional lipid ratios were as strong as the ApoB:ApoA-I ratio in predicting CVD risk. The data provide little evidence for replacement of traditional lipids and their ratios with measures of ApoB, ApoA-I and their ratio.

Correlation of thromboelastography with standard tests of anticoagulation in paediatric patients receiving extracorporeal life support.

UNLABELLED: Children requiring extracorporeal life support (ECLS) are at significant risk for thrombotic and haemorrhagic complications. Thromboelastography (TEG) is increasingly being used to assist in monitoring the coagulation status of critically ill patients. Its role in heparinised children receiving ECLS is unknown. METHODS: A retrospective review of TEG in 27 children (mean age 2 years and 8 months) receiving ECLS in a tertiary paediatric intensive care unit between December 2006 and April 2008. Paired TEG (kaolin and heparinase) analysis was performed on 171 occasions. On all occasions activated partial thromboplastin time (APTT) and platelet count were performed within 4 hours of the TEG (mean 6.5 minutes after TEG). On 158 occasions, the activated clotting time (ACT) was measured simultaneously with TEG. RESULTS: The TEG (kaolin) sample was not interpretable due to the heparin effect in 89 (52%) samples. There was a weak correlation between TEG (heparinase) variables and APTT, and between TEG and ACT with a stronger correlation between TEG (Maximum amplitude) and platelet count. CONCLUSION: TEG monitoring should always include paired samples in heparinised children on ECLS. In this heterogeneous population, weak, and moderate correlations exist between TEG and standard haematological tests. Prospective studies, with simultaneous sampling for TEG and conventional laboratory tests, must be performed in order to establish its absolute utility as a clinical tool in this population.

Zebrafish: An in vivo model for the study of neurological diseases.

As the population ages, there is a growing need for effective therapies for the treatment of neurological diseases. A limited number of therapeutics are currently available to improve cognitive function and research is limited by the need for in vivo models. Zebrafish have recently become a focus of neurobehavioral studies since larvae display neuropathological and behavioral phenotypes that are quantifiable and relate to those seen in man. Due to the small size of Zebrafish larvae, assays can be undertaken in 96 well plates and as the larvae can live in as little as 200 mul of fluid, only a few milligrams of compound are needed for screening. Thus in vivo analysis of the effects of compounds can be undertaken at much earlier stages in the drug discovery process. This review will look at the utility of the zebrafish in the study of neurological diseases and its role in improving the throughput of candidate compounds in in vivo screens.

Australian Aboriginal people and Torres Strait Islanders have an atherogenic lipid profile that is characterised by low HDL-cholesterol level and small LDL particles.

AIM: To characterise lipid profiles for Australian Aboriginal people and Torres Strait Islanders. METHODS: Community-based, cross-sectional surveys in 1995-1997 including: 407 female and 322 male Australian Aboriginal people and 207 female and 186 male Torres Strait Islanders over 15 years old. A comparator of 78 female (44 with diabetes) and 148 male (73 with diabetes) non-indigenous participants recruited to clinical epidemiological studies was used. Lipids were determined by standard assays and LDL diameter by gradient gel electrophoresis. RESULTS: Diabetes prevalence was 14.8% and 22.6% among Aboriginal people and Torres Strait Islanders, respectively. LDL size (mean [95% CI (confidence interval)]) was smaller (P<0.05) in non-diabetic Aboriginal (26.02 [25.96-26.07] nm) and Torres Strait Islander women (26.01 [25.92-26.09] nm) than in non-diabetic non-indigenous women (26.29 [26.13-26.44] nm). LDL size correlated (P<0.0005) inversely with triglyceride, WHR, and fasting insulin and positively with HDL-cholesterol. HDL-cholesterol (mean [95% CI] mmol/L) was lower (P<0.0005) in indigenous Australians than in non-indigenous subjects, independent of age, sex, diabetes, WHR, insulin, triglyceride, and LDL size: Aboriginal (non-diabetic women, 0.86 [0.84-0.88]; diabetic women, 0.76 [0.72-0.80]; non-diabetic men, 0.79 [0.76-0.81]; diabetic men, 0.76 [0.71-0.82]); Torres Strait Islander (non-diabetic women, 1.00 [0.95-1.04]; diabetic women, 0.89 [0.83-0.96]; non-diabetic men, 1.00 [0.95-1.04]; diabetic men, 0.87 [0.79-0.96]); non-indigenous (non-diabetic women, 1.49 [1.33-1.67]; diabetic women, 1.12 [1.03-1.21]; non-diabetic men, 1.18 [1.11-1.25]; diabetic men, 1.05 [0.98-1.12]). CONCLUSIONS: Indigenous Australians have a dyslipidaemia which includes small LDL and very low HDL-cholesterol levels. The dyslipidaemia was equally severe in both genders. Strategies aimed at increasing HDL-cholesterol and LDL size may reduce high CVD risk for indigenous populations.

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes.

AIMS: To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. METHODS: Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. RESULTS: PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427). CONCLUSIONS: In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.

Differential association of C-reactive protein with adiposity in men and women in an Aboriginal community in northeast Arnhem Land of Australia.

OBJECTIVE: To examine the relationship between C-reactive protein (CRP), adiposity and other metabolic abnormalities in an Aboriginal community in Northern Australia. DESIGN: Cross-sectional analysis of data obtained between 2001 and 2003 from 379 Aboriginal people residing in a geographically isolated community. RESULTS: Mean (95% CI) CRP in women and men was 4.06 cholesterol (3.53, 4.66) mg/l and 3.42 (2.94, 3.97) mg/l, respectively (P=NS). The prevalence of the metabolic syndrome (US National Cholesterol Education [corrected] Program (NCEP) definition) was significantly higher for women than men (41 vs 18%, chi (2)=20.94, P<0.001). C-reactive protein correlated strongly with adiposity in women (waist circumference, waist to hip ratio and body mass index; r>/=0.514, P<0.01) but much less strongly in men (r

Widespread vascular production of C-reactive protein (CRP) and a relationship between serum CRP, plaque CRP and intimal hypertrophy.

OBJECTIVES: Evidence of local vascular production and a relationship between serum hsCRP levels and tissue expression of CRP in subjects with vascular disease would support a direct role for CRP in atherosclerosis. METHODS AND RESULTS: Vascular tissue from subjects undergoing coronary artery bypass grafting surgery (CABGS) (n=28) and carotid endarterectomy (CEA) (n=25) were studied. Histological samples were assessed for intima-media ratio (IMR) and CRP by immunohistochemistry. CRP mRNA was quantified by real-time polymerase chain reaction. CRP mRNA was seen in all plaques, non-atherosclerotic artery and atrium but no difference in mRNA expression was seen between plaque and non-atherosclerotic tissue. Serum hsCRP correlated with IMR (r=0.64, p=0.001) in non-atherosclerotic arteries and with plaque CRP staining (r=0.57, p=0.009) independent of age, BMI, lipids, diabetes and blood pressure. In a separate patient series, serum hsCRP was measured in aortic and coronary sinus blood from subjects undergoing CABGS or angiography (n=54). There was a coronary circulation hsCRP gradient ([mean+/-S.E.M.] aortic CRP 4.3mg/l+/-0.8 versus coronary sinus 5.8+/-1.2mg/l, p<0.05). CONCLUSIONS: Widespread vascular CRP mRNA expression, a correlation between serum hsCRP, intimal hypertrophy and plaque CRP, and a coronary hsCRP gradient suggest vascular secretion may contribute to serum CRP levels.

Traditional risk factor assessment does not capture the extent of cardiovascular risk in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerosis. However, the degree of endothelial dysfunction and its relationship to traditional and novel cardiovascular risk factors have not been examined in SLE. METHODS: In a case-control design, 35 patients with clinically stable SLE and 35 control subjects matched for age, sex, body mass index and smoking status were studied. Arterial elasticity, lipid profile, homocysteine, measures of inflammation and oxidative stress were determined. RESULTS: Among traditional vascular risk factors, there was a nonsignificant trend towards lower blood pressure in the control subjects, whereas low-density lipoprotein (LDL) cholesterol levels were significantly lower in the SLE group (2.5 vs 3.3 mmol/L, P < 0.001). Patients with SLE had significantly lower small artery elasticity (SAE; 4.9 vs 7.0 ml/mmHg x 100, P < 0.001) and higher plasma homocysteine (11.4 vs 8.3 mmol/L, P = 0.002) than control subjects. Levels of serum sVCAM-1 (614 vs 494 ng/mL, P = 0.002), oxidized LDL (144 vs 97, P < 0.001) and CD40 ligand (4385 vs 1373 pg/ml, P = 0.001) were significantly higher in SLE. Oxidized LDL levels, older age at SLE diagnosis and higher disease damage scores correlated inversely with SAE but not traditional risk factors. CONCLUSION: Impaired endothelial function as shown by decreased SAE, and an adverse profile of novel proatherogenic and prothrombotic vascular disease risk factors were prevalent in clinically quiescent SLE. These findings show the vulnerability of patients with SLE for atherosclerosis, and emphasize that assessments based on traditional risk factors alone may be inadequate.

The metabolic syndrome and changing relationship between blood pressure and insulin with age, as observed in Aboriginal and Torres Strait Islander peoples.

AIMS: To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age. METHODS: A cross-sectional population-based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2-h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids. RESULTS: The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15-29 years, and an inverse correlation for Aborigines aged 40 years and older. CONCLUSION: Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin.

Plasma low-molecular weight fluorescence in type 1 diabetes mellitus.

Characteristic tissue fluorescence is associated with advanced glycation end product (AGE) accumulation in experimental diabetes models, but its utility in patients with type 1 diabetes remains to be established. We studied 148 patients with type 1 diabetes and 77 healthy age-matched control subjects. Low-molecular weight (LMW) fluorophore levels were estimated in plasma samples obtained after an overnight fast. Intra- and interassay coefficients of variation were 4.7% and 6.4%, respectively. LMW fluorophore levels were significantly higher in patients with diabetes than in control subjects (6.3 +/- 0.6 AU/mL vs. 4.1 +/- 0.3; P = 0.007). However, all of this difference came from patients with microvascular complications (n = 67, 7.5 +/- 1.3). There was no significant difference in LMW fluorescence between complication-free patients (4.4 +/- 0.2) and control subjects (P > 0.05). On multivariate analysis, LMW fluorophores correlated with measures of renal function (P < 0.05) but not with diabetes per se. In addition, there was no correlation between LMW fluorophores and the markers of oxidative stress or systemic inflammation. Longitudinal and interventional studies are required to determine whether the association between LMW fluorophores and nephropathy is cause or effect.

Oxidized LDL and small LDL particle size are independently predictive of a selective defect in microcirculatory endothelial function in type 2 diabetes.

AIM: To explore the associations of LDL (low-density lipoprotein) particle size and oxidized LDL with endothelium-dependent function of the forearm microcirculation in diabetes. METHODS: Endothelium-dependent function was examined in 43 middle-aged men and women with type 2 diabetes and 10 age-matched controls. All received aspirin to inhibit endothelial cyclo-oxygenase. Forearm blood flow (FBF) was measured using venous occlusion plethysmography with separate administration of acetylcholine (ACh) and bradykinin (BK) into the brachial artery. Endothelium-independent function was assessed using sodium nitroprusside (SNP). N(G)-monomethyl-L-arginine (L-NMMA) was co-infused with ACh (ACh + L-NMMA) and BK (BK + L-NMMA) to assess non-NO-mediated contributions to endothelium-dependent function. RESULTS: Subjects with diabetes had impaired endothelium-dependent and endothelium-independent function compared with controls (p < 0.01 for ACh, BK and SNP). In multivariate regression analysis, LDL size (r = 0.41 and p = 0.007), oxidized LDL (r = -0.41 and p = 0.007) and duration of diabetes (r = -0.37 and p = 0.02) predicted FBF response to ACh independently of age, gender and systolic blood pressure. There were no associations between LDL size, oxidized LDL, duration of diabetes and FBF response to BK, SNP, ACh + L-NMMA or BK + L-NMMA. CONCLUSION: In type 2 diabetes, small dense LDL particles, duration of diabetes and oxidized LDL may independently contribute to endothelial dysfunction of the microcirculation. These disturbances may occur via a selective defect, because ACh and BK activate endothelial NO synthase via different G-protein signal transduction pathways.

Expression of GLUT12 in the fetal membranes of the human placenta.

The aim of this study was to characterize the expression of the novel glucose transporter GLUT12 in the fetal membranes of the human placenta. RT-PCR and Western blotting of extracts of amnion and choriodecidua from four normal term placentas identified GLUT12 mRNA and protein expression. In all four samples the signals for GLUT12 were markedly stronger in the choriodecidua than in the amnion, whereas the signals for GLUT1, a glucose transporter know to be expressed in fetal membranes, were similar for the two tissues. In further studies, paraffin sections of fetal membranes were analyzed by immunohistochemistry with GLUT12 and GLUT1-specific polyclonal antibodies. GLUT12 immunoreactivity was localized predominantly to the trophoblast cells in the chorion and to a lesser extent to decidual cells and to epithelial and fibroblast cells of the amnion. GLUT1 was localized to chorionic trophoblast cells and amniotic epithelial and fibroblast cells. GLUT12 expression was predominantly cytoplasmic, whereas GLUT1 was associated with the membrane of the cells. These results show that GLUT12 is expressed in cells of human fetal membranes and suggest that GLUT12 may play a role in the facilitation of glucose transport into these cells.

Lipoproteins and diabetic microvascular complications.

Risk factors for the microvascular complications (nephropathy and retinopathy) of Type 1 and Type 2 diabetes mellitus and the associated accelerated atherosclerosis include: age, diabetes duration, genetic factors, hyperglycaemia, hypertension, smoking, inflammation, glycation and oxidative stress and dyslipoproteinaemia. Hypertriglyceridaemia, low HDL and small dense LDL are common features of Type 2 diabetes and Type 1 diabetes with poor glycaemic control or renal complications. With the expansion of knowledge and of clinical and research laboratory tools, a broader definition of 'lipid' abnormalities in diabetes is appropriate. Dyslipoproteinaemia encompasses alterations in lipid levels, lipoprotein subclass distribution, composition (including modifications such as non-enzymatic glycation and oxidative damage), lipoprotein-related enzymes, and receptor interactions and subsequent cell signaling. Alterations occur in all lipoprotein classes; chylomicrons, VLDL, LDL, HDL, and Lp(a). There is also emerging evidence implicating lipoprotein related genotypes in the development of diabetic nephropathy and retinopathy. Lipoprotein related mechanisms associated with damage to the cardiovascular system may also be relevant to damage to the renal and ocular microvasculature. Adverse tissue effects are mediated by both alterations in lipoprotein function and adverse cellular responses. Recognition and treatment of lipoprotein-related risk factors, supported by an increasing array of assays and therapeutic agents, may facilitate early recognition and treatment of high complication risk diabetic patients. Further clinical and basic research, including intervention trials, is warranted to guide clinical practice. Optimal lipoprotein management, as part of a multi-faceted approach to diabetes care, may reduce the excessive personal and economic burden of microvascular complications and the related accelerated atherosclerosis.

GLUT12 expression in human placenta in first trimester and term.

The aim of this study was to characterize the expression of a novel glucose transporter protein GLUT12 in human placenta. GLUT12 mRNA expression was identified by RT-PCR in extracts from five normal term placentae and in extracts from cultured cells of the JAR, JEG-3 and HTR-8Svneo cell lines. In further studies, paraffin sections of first trimester tissue from chorionic villus sampling and term tissue obtained after delivery were analysed by immunohistology with a GLUT12 specific polyclonal antibody. GLUT12 immunoreactivity was expressed predominantly in the syncytiotrophoblast and in extra-villous trophoblast cells in first trimester tissues at 10, 11 and 12 weeks' gestation. In term tissue, however, GLUT12 staining was not detected in syncytiotrophoblast and was found predominantly in villous vascular smooth muscle cells and villous stromal cells. These results suggest that there is a dynamic spatial and temporal expression pattern for the novel glucose transporter GLUT12 in human placenta.

Effects of monounsaturated enriched sunflower oil on CHD risk factors including LDL size and copper-induced LDL oxidation.

OBJECTIVE: To compare the effects of a diet high in monounsaturated enriched sunflower oil and a low fat diet on CHD risk factors including in vitro Cu-induced LDL oxidation and LDL size, lipids, lipoproteins, glucose and insulin. DESIGN: A randomized crossover dietary intervention. SETTING: Free living individuals. SUBJECTS: Fourteen healthy males 35 to 55 years of age and 14 healthy postmenopausal women 50 to 60 years of age completed the dietary intervention. Two subjects did not complete the study, and their data were not included. INTERVENTIONS: A low fat, high carbohydrate diet (22% to 25% of energy from total fat, 7% to 8% of energy from monounsaturated fat and 55% to 60% of energy from carbohydrate) was compared to a monounsatutated enriched sunflower oil (MO) diet (40% to 42% of energy from fat, with 26% to 28% from monounsaturated fat and 40% to 45% of energy from carbohydrate) in an isocaloric substitution. Each dietary period was one month. RESULTS: Total cholesterol, LDL cholesterol, triglycerides and glucose were not significantly different between the two diets. HDL cholesterol, HDL3 cholesterol and insulin were significantly higher on the MO diet, mean 7%, 7% and 17% higher respectively. Copper-induced LDL oxidation lag phase was significantly longer (mean 18%) after the MO diet compared to the low fat, high carbohydrate diet. LDL particle size was not significantly different. CONCLUSIONS: The significant increase in LDL oxidation lag phase and the significantly higher HDL cholesterol on the MO diet would be expected to be associated with a decrease in CHD risk.

Insulin resistance as a major determinant of increased coronary heart disease risk in postmenopausal women with Type 2 diabetes mellitus.

AIM: To investigate the risk factors associated with clinically defined coronary heart disease (CHD) in women with Type 2 diabetes mellitus (DM). METHODS: CHD status was assessed via standard history and resting electrocardiogram in 41 postmenopausal diabetic and 41 age- and body mass index-matched normoglycaemic women recruited from a community-based cohort. The following parameters were assessed: body composition by dual energy X-ray absorptiometry, blood pressure, metabolic and lipoprotein profile and haemostatic factors. RESULTS: Diabetic women with CHD (n = 14) had greater insulin resistance, calculated by homeostasis model assessment (10.2 (7.0-14.8) vs. 6.5 (5.5-7.7), P = 0.010), and higher plasminogen activator inhibitor-1 (PAI-1) levels (45 (29-69) vs. 24 (19-32) ng/ml, P = 0.013), than those without CHD. They also had higher triglycerides (2.9 (2.2-3.8) vs. 2.1 (1.8-2.4) mmol/l, P = 0.016) and a trend towards reduced low-density lipoprotein particle size (25.5 +/- 0.6 vs. 25.8 +/- 0.5 nm, P = 0.097). In a logistic regression model, insulin resistance was a significant independent predictor of CHD status (odds ratio = 1.33, 95% confidence interval = 1.06-1.68, P = 0.015). In contrast, in normoglycaemic women the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B and systolic blood pressure (P = 0.018, P = 0.016, P = 0.006 and P = 0.049, respectively). CONCLUSIONS: Increased insulin resistance in association with elevated PAI-1 and dyslipidaemia appears to underpin the increased risk of CHD in women with Type 2 DM. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group. Diabet. Med. 18, 476-482 (2001)