Associations of erythrocyte membrane fatty acids with the concentrations of C-reactive protein, interleukin 1 receptor antagonist and adiponectin in 1373 men.

Dietary and endogenous fatty acids could play a role in low-grade inflammation. In this cross-sectional study the proportions of erythrocyte membrane fatty acids (EMFA) and the concentrations of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra) and adiponectin were measured and their confounder-adjusted associations examined in 1373 randomly selected Finnish men aged 45-70 years participating in the population based Metsim study in Eastern Finland. The sum of n-6 EMFAs, without linoleic acid (LA), was positively associated with concentrations of CRP and IL-1Ra (r partial=0.139 and r partial=0.115, P<0.001). These associations were especially strong among lean men (waist circumference <94 cm; r partial=0.156 and r partial=0.189, P<0.001). Total n-3 EMFAs correlated inversely with concentrations of CRP (r partial=-0.098, P<0.001). Palmitoleic acid (16:1n-7) correlated positively with CRP (r partial=0.096, P<0.001). Cis-vaccenic acid (18:1n-7) was associated with high concentrations of adiponectin (r partial=0.139, P<0.001). In conclusion, n-6 EMFAs, except for LA, correlated positively with the inflammatory markers. Palmitoleic acid was associated with CRP, whereas, interestingly, its elongation product, cis-vaccenic acid, associated with anti-inflammatory adiponectin.

Semisolid meal enriched in oat bran decreases plasma glucose and insulin levels, but does not change gastrointestinal peptide responses or short-term appetite in healthy subjects.

BACKGROUND AND AIMS: Dietary fibre (DF) may play an important role in weight control. The amount, type and way of processing of DF modify food structure and subsequent postprandial appetitive, metabolic and hormonal effects, but current understanding about the magnitude of effects that specific types and amounts of DF exert are still poorly understood. METHODS AND RESULTS: We investigated the effects of wheat and oat brans alone and as combination in semisolid food matrix on postprandial appetite profile and gastrointestinal (GI) hormonal responses. Twenty healthy, normal-weight subjects (5 male/15 female, aged 23.3 ± 0.85y) participated in the study. Isoenergetic and isovolumic (1250 kJ, 300 g) puddings with different insoluble and soluble DF content were tested in a randomised order: pudding with 1) no added fibre, 2) 10 g wheat bran DF, 3) 10 g oat bran DF and 4) combination including 5 g wheat bran DF + 5 g oat bran DF. Blood samples were drawn before and 15, 30, 45, 60, 90, 120 and 180 min after the test meals to determine plasma glucose, ghrelin, peptide YY (PYY) and serum insulin concentrations. Subjective profiles of appetite were assessed using visual analogue scales (VAS). Plasma glucose (P = 0.001) and serum insulin (P < 0.001) responses were the lowest after the pudding with the greatest amount of ß-glucan. In contrast, postprandial ghrelin or PYY responses or appetite sensations did not differ among the meals. CONCLUSION: Oat ß-glucan decreased postprandial plasma glucose and serum insulin responses, yet had no significant effects on GI peptide responses or appetite ratings.

Moderate increase in dietary sucrose does not influence fasting or postprandial serum lipids regardless of the presence of apolipoprotein E2 allele in healthy subjects.

OBJECTIVE: To investigate whether a moderate increase in dietary sucrose intake induces different serum lipid responses in normolipidemic subjects with the epsilon 2 allele compared with subjects without the epsilon 2 allele. DESIGN: Controlled, parallel study. SUBJECTS: There were 15 subjects with the apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE 3/3 or 3/4 genotype, whose mean+/-s.d. age was 48+/-14 and 35+/-10 years, respectively. All subjects had normal glucose metabolism. INTERVENTIONS: The subjects were instructed to increase their sucrose intake by 40 g/day for 8 weeks and to decrease the intake of saturated and unsaturated fat to maintain energy balance. Dietary adherence was monitored using food records and the actual increase in sucrose intake was 39.8+/-18.4 g/day. Sixteen subjects (nine with APOE 3/2 genotype, seven with APOE 3/3 or 3/4 genotypes) participated also in an 8 h oral fat tolerance test at the beginning and at the end of the intervention. RESULTS: Body weight remained stable during the intervention. Sucrose intake did not have a significant effect on fasting concentrations of serum total and lipoprotein lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in either genotype group. Neither were there any changes in postprandial lipid or insulin responses. CONCLUSIONS: Moderate increase in sucrose intake does not affect fasting or postprandial serum lipid responses in healthy subjects with or without the epsilon 2 allele.

Tolerance of symptomatic lactose malabsorbers to lactose in milk chocolate.

OBJECTIVE: To study tolerance to lactose in milk chocolate among symptomatic lactose maldigesters. DESIGN: Randomized cross-over study. SUBJECTS: Twenty-seven adult lactose maldigesters with symptomatic lactose intolerance. METHODS: A 100 g chocolate sample prepared with whole milk (12 g lactose), whole-milk powder (12 g lactose), low-lactose milk powder (2 g lactose) or lactose-free milk powder was eaten after an overnight fast. Gastrointestinal symptoms (flatulence, abdominal bloating, abdominal pain, borgorygmi and nausea) were recorded in a questionnaire during the following 8 h. Bowel movements and stool consistency were also registered during the test day. RESULTS: The numbers of persons reporting different gastrointestinal symptoms or any of the symptoms did not differ significantly after eating the chocolate samples. No statistical differences were found in the estimated strength of the different symptoms or the total strength of all symptoms combined. Differences in the bowel frequency and stool consistency were also non-significant. CONCLUSIONS: Lactose malabsorbers with self-reported lactose intolerence did not differ in their response to milk chocolate samples containing different amounts of lactose.

Effect of the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue of massively obese subjects.

The aim was to study the effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on the expression of PPARgamma target genes in adipose tissue. Adipose tissue samples were collected from 30 massively obese subjects (10 men and 20 women) from omental, sc abdominal, and femoral depots. The mRNA expression of PPARgamma1, PPARgamma2, lipoprotein lipase, p85alpha phosphatidylinositol 3-kinase, and uncoupling protein 2 were quantified by reverse transcription-competitive PCR. The genotypes of Pro12Ala polymorphism were determined by single-strand conformation polymorphism analysis. The frequency of the Ala12 allele was 13.3% (8 Pro12Ala and 22 Pro12Pro). There were no differences in body weight, fat mass, and fasting serum leptin between the genotypes. The mRNA expression of p85alpha phosphatidylinositol 3-kinase was significantly lower in the omental fat of the Pro12Ala carriers than the Pro12Pro carriers (P < 0.01). It also appeared that PPARgamma2 expression was higher in men with Ala12 allele (P < 0.01). Interestingly, particularly in women, the expression of both PPARgamma splice variants was lower in omental than sc fat independently of the genotype (P < 0.05-0.01). The common Pro12Ala polymorphism of the PPARgamma2 gene has minor influence on mRNA expression of PPARgamma target genes in adipose tissue of obese subjects. Expression of both PPARgamma splice variants is dependent on fat depot: omental fat shows lower mRNA levels, compared with sc fat depots.

Association of the PRO12ALA polymorphism of the PPAR-gamma2 gene with oxidized low-density lipoprotein and cardiolipin autoantibodies in nondiabetic and type 2 diabetic subjects.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a key component in adipocyte differentiation and fat-specific gene expression and may modulate macrophage functions, like proinflammatory activities, and stimulate oxidized low-density lipoprotein (ox-LDL) uptake. We hypothesized that the Pro12Ala polymorphism of the PPAR-gamma2 gene may affect the immune response to ox-LDL. Therefore, we investigated the association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with ox-LDL autoantibodies, as well anticardiolipin antibodies, in a 10-year prospective study. The Pro12Ala polymorphism was genotyped in 119 nondiabetic subjects (age, 45 to 64 years; body mass index [BMI], 19 to 46 kg/m(2)) and 70 type 2 diabetic patients (age, 45 to 65 years; BMI, 19 to 46 kg/m(2)) by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method. Ox-LDL autoantibodies and anticardiolipin antibodies were determined at baseline and after 10 years of follow-up. At baseline, the Pro12Ala polymorphism was not associated with ox-LDL autoantibodies in nondiabetic subjects, whereas type 2 diabetic patients having the Pro12Ala or the Ala12Ala genotypes tended to have higher levels of ox-LDL autoantibodies than did type 2 diabetic patients with the Pro12Pro genotype. At the 10-year follow-up, diabetic subjects having the Ala12 allele had higher ox-LDL autoantibody levels than did diabetic subjects with the Pro12Pro genotype (P =.043 after adjustment for age, gender, BMI, and hemoglobin A(1c) [HbA(1c)] at 5 years). In nondiabetic subjects and regarding anticardiolipin antibodies, no such relationship was observed. We conclude that the Pro12Ala polymorphism of the PPAR-gamma2 gene was associated with increased ox-LDL autoantibodies in type 2 diabetic subjects. Genotype may therefore modulate the oxidative modification of LDL in hyperglycemic milieu.

The effect of vegetable oil-based cheese on serum total and lipoprotein lipids.

OBJECTIVE: To investigate the effect of rapeseed oil-based cheese (milk-fat substituted by rapeseed oil) on serum total and lipoprotein lipid concentrations and blood pressure in reference to ordinary, milk-fat-based cheese in subjects with mildly to moderately elevated serum cholesterol concentration. DESIGN: Randomized, controlled, single-blind, cross-over clinical trial. SETTINGS: Outpatient dietary intervention with free-living subjects in Eastern Finland. INTERVENTIONS: The study began with a 2 week pre-trial period followed by two 4 week intervention periods. During the intervention study subjects replaced their ordinary cheese or cold cuts with 65 g of rapeseed oil-based or milk-fat-based control cheese. The type of test cheese was switched at 4 weeks of intervention. Altogether 31 subjects completed the study. RESULTS: Compared with the control cheese period the mean serum total cholesterol concentration was 6.7% (95% Cl -9.9 to -3.5%) lower after 2 weeks and 5.0% (95% Cl -7.5 to -2.5%) lower after 4 weeks of use of rapeseed oil-based cheese. Respectively, LDL cholesterol concentration was 7.0% (95% Cl -11.7 to -2.6%) lower after 2 weeks use and 6.4% (95% Cl -10.0 to -2.8%) lower after 4 weeks' use of rapeseed oil-based cheese. CONCLUSIONS: The present study showed that the rapeseed oil-based cheese reduces serum total and LDL cholesterol concentrations in mildly to moderately hypercholesterolemic subjects when replacing ordinary milk-fat-based cheese in the diet. SPONSORSHIP: Mildola Ltd, Tuusula, Finland and Kyrönmaan Juustomestarit Ltd, lsokyrö, Finland.

Variation in the fatty acid binding protein 2 gene is not associated with markers of metabolic syndrome in patients with coronary heart disease.

BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of the intestinal fatty acid binding protein 2 (FABP2) gene is associated with insulin resistance and affects the fatty acid composition of serum lipids. Our aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of the FABP2 gene in patients with coronary heart disease (CHD), and the association between the polymorphism and the markers of metabolic syndrome, serum lipid levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) Study. Markers of metabolic syndrome included fasting plasma glucose concentration, serum high-density lipoprotein cholesterol and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in the CHD patients (27.2%) and control subjects from two independent studies (27.8% and 28.7%). There were no significant differences in plasma glucose, serum lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes. Genotype frequency was not associated with the prevalence of diabetes or metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol Education Program criteria) tended to be more frequent in subjects with the Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid profiles of serum cholesteryl esters, TG or phospholipids among the genotypes. CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids in Finnish CHD patients.

A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference.

METHODS: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m(2)) and waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. RESULTS: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. CONCLUSIONS: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.

No harm from five year ingestion of oats in coeliac disease.

BACKGROUND: Six to 12 months of ingestion of moderate amounts of oats does not have a harmful effect in adult patients with coeliac disease. As the safety of long term intake of oats in coeliac patients is not known, we continued our previous 6-12 month study for five years. AIM: To assess the safety of long term ingestion of oats in the diet of coeliac patients. PATIENTS: In our previous study, the effects of a gluten free diet and a gluten free diet including oats were compared in a randomised trial involving 92 adult patients with coeliac disease (45 in the oats group, 47 in the control group). After the initial phase of 6-12 months, patients in the oats group were allowed to eat oats freely in conjunction with an otherwise gluten free diet. After five years, 35 patients in the original oats group (23 still on an oats diet) and 28 in the control group on a conventional gluten free diet were examined. METHODS: Clinical and nutritional assessment, duodenal biopsies for conventional histopathology and histomorphometry, and measurement of antiendomysial, antireticulin, and antigliadin antibodies. RESULTS: There were no significant differences between controls and those patients consuming oats with respect to duodenal villous architecture, inflammatory cell infiltration of the duodenal mucosa, or antibody titres after five years of follow up. In both groups histological and histomorphometric indexes improved equally with time. CONCLUSIONS: This study provides the first evidence of the long term safety of oats as part of a coeliac diet in adult patients with coeliac disease. It also appears that the majority of coeliac patients prefer oats in their diet.

The impact of the leucine 7 to proline 7 polymorphism of the neuropeptide Y gene on postprandial lipemia and on the response of serum total and lipoprotein lipids to a reduced fat diet.

OBJECTIVE: The aim of the study was to examine the impact of the leucine7 to proline7 (Leu7Pro) polymorphism of the NPY gene on postprandial (PP) lipemia, post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and the response of serum lipids to a reduced fat diet. DESIGN AND SUBJECTS: Seven middle-aged obese subjects with Leu7Pro genotype were matched with seven subjects with Leu7Leu genotype for gender, age, apolipoprotein E phenotype and BMI. These 14 subjects participated in the oral 8 h fat tolerance test. Sixty-eight slightly obese middle-aged subjects (10 with the Leu7Pro genotype) had participated in intervention studies and consumed a reduced fat diet for 8 weeks. RESULTS: There were no statistically significant differences in PP areas under the curve of plasma total triglycerides (TG), chylomicron TG, VLDL-TG or insulin between the genotype groups. The TG-to-cholesterol (C) ratio in VLDL was significantly lower in the subjects with Leu7Pro genotype compared to those with the Leu7Leu genotype at time points 30 min and 1 h in the fat tolerance test. Heparin-induced activities of LPL or HL or the response of serum total or LDL-C to the reduced fat diet did not differ between the groups. CONCLUSIONS: The NPY genotype neither affects the magnitude of postprandial lipemia induced by a fat tolerance test nor the response of serum total lipids or lipids in different lipoprotein classes to the reduced fat diet. However, this preliminary study suggests that there might be compositional differences in the lipoprotein particles between the genotype groups that affect postprandial lipid metabolism. SPONSORSHIP: The Council for Health Sciences of the Academy of Finland, Kuopio University Hospital and the National Technology Agency, Finland.

Hormone sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss.

OBJECTIVE: The effect of weight reduction on hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) gene expression and their relationship with adipose tissue metabolism were studied in massively obese men and women. SUBJECTS: Seventeen obese subjects (eight men, nine women) participated in the study (age 44+/-2 y, weight 145+/-8 kg, fat 40+/-2% of body mass, mean+/-s.e.m.), who were going through a gastric-banding operation for weight reduction. MEASUREMENTS: HSL and LPL mRNA expressions were analyzed using the reverse transcription competitive polymerase chain reaction. Subcutaneous fat lipolysis was measured in vivo by microdialysis and in vitro in isolated subcutaneous abdominal adipocytes. Measurements were done before and after 1 y of weight reduction. RESULTS: Significant reductions in weight (for men -20.3+/-2.5%, for women -18.3+/-2.1% (mean+/-s.e.m.) and fat mass (for men -27.6+/-7.9%, for women -21.8+/-3.9%) were observed in both genders. In women HSL mRNA expression decreased by 31% (P=0.008) and LPL expression increased slightly, but nonsignificantly (42%, P=0.110). These changes were not observed in men. In men, inhibition of lipolysis with alpha(2)-adrenergic and adenosine agonist was improved (P=0.001) in isolated adipocytes. CONCLUSIONS: This study uncovers new differences between genders in adipocyte metabolism along with weight reduction. In women, the observed changes in HSL and LPL gene expression suggest that deposition of lipids into adipose tissue might be favored after weight reduction. In men, the results indicate improved responsiveness to inhibition in adipose tissue metabolism along with weight reduction.

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Leucine7 to proline7 polymorphism in the preproneuropeptide Y is associated with the progression of carotid atherosclerosis, blood pressure and serum lipids in Finnish men.

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preproneuropeptide Y (prepro-NPY) gene signal peptide may be important in blood pressure regulation, cholesterol metabolism and the pathogenesis of atherosclerosis in humans. We examined the associations of the Leu7Pro polymorphism with carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42-60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated four-year increase in the mean (P=0.01) and maximal (P=0.007) common carotid intima-media thickness (IMT) and with slightly increased systolic (P=0.03) and diastolic (P=0.02) blood pressures, adjusted for other major risk factors. Men with Pro7 substitution had 30.6% (95% CI 6.9-54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3-34.4%) greater increase in the maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol (P=0.01) and LDL cholesterol (P=0.02) in obese (body mass index (BMI)>30 kg/m(2)) men. This study provides important evidence suggesting that the Pro7 substitution in the prepro-NPY is an important risk factor for accelerated atherosclerotic progression, increased blood pressure and increased serum cholesterol in humans.

Sterol regulatory element binding protein 1c (SREBP-1c) expression in human obesity.

OBJECTIVE: Investigation of the expression of sterol regulatory element binding protein-1c (SREBP-1c) in different adipose tissue depots in morbidly obese subjects before and after 1 year of weight loss induced by gastric banding operation. RESEARCH METHODS AND PROCEDURES: SREBP-1c expression was studied in 20 massively obese subjects (6 men and 14 women; age: 41 +/- 9 years; weight: 148 +/- 34 kg; percentage of body fat: 42 +/- 4; mean +/- SD) using reverse transcription competitive polymerase chain reaction. Adipose tissue biopsies were taken from omental, subcutaneous abdominal, and femoral depots before weight loss, and from subcutaneous depots after weight loss. Subcutaneous samples were taken also from 6 normal weight subjects. RESULTS: The level of SREBP-1c mRNA was significantly lower in omental (1.8 +/- 0.2 amol/microg of total RNA) than in subcutaneous abdominal (3.7 +/- 0.4 amol/microg of total RNA) or femoral (3.9 +/- 0.4 amol/microg of total RNA; p < 0.001, mean +/- SEM) depots. The values in subcutaneous depots were about twice as high in normal weight (7.4 +/- 2.5 for abdominal and 6.5 +/- 1.5 for femoral, p < 0.01) as in obese subjects. After weight loss, the mRNA levels of SREBP-1c increased in obese subjects, both in subcutaneous abdominal (5.3 +/- 0.7, p < 0.01) and in femoral (4.8 +/- 0.8, p < 0.05) tissue. DISCUSSION: SREBP-1c mRNA expression was lower in omental adipose tissue than in subcutaneous depots in obese subjects before weight loss. Furthermore, the expression of SREBP-1c in obese subjects was clearly lower than in normal weight subjects, but mRNA levels increased along with weight reduction. Weight reduction was associated with increased mRNA levels of SREBP-1c in obese subjects. The reduced expression of SREBP-1c in obesity could be ascribed to lowered action or concentration of insulin, changeable along with weight reduction. However, changes in SREBP-1c expression after weight reduction could also be ascribed to the changes in calorie intake or nutritional habits after gastric banding operation.

Myocardial fatty acid oxidation in patients with impaired glucose tolerance.

AIMS/HYPOTHESIS: Fatty acids are an important source of energy in the myocardium. Abnormal myocardial fatty acid metabolism could contribute to the deterioration of cardiac function frequently observed in patients with Type II (non-insulin-dependent) diabetes mellitus. In our previous study, myocardial total uptake of non-esterified fatty acid (NEFA) was measured in patients with impaired glucose tolerance and found to be normal. This study aimed to investigate the subsequent metabolic steps and beta-oxidation of NEFA. METHODS: A total of 6 men with impaired fasting glucose (age 50 +/- 2 years, BMI 29 +/- 1 kg/m2, means +/- SEM) and 6 healthy men (50 +/- 1 years, 25 +/- 1 kg/ m2) were studied in the fasting state. Myocardial blood flow was measured with [15O]H2O and positron emission tomography and myocardial NEFA metabolism with [11C]palmitic acid. RESULTS: Myocardial blood flow was normal and not different between the impaired glucose tolerance and the control group (78 +/- 6 vs 73 +/- 13 ml/100 g/ min, NS). The [11C]palmitic acid uptake indices were similar between the groups (10.4 +/- 0.5 vs 11.2 +/- 0.8 ml/100 g/min, respectively, NS). The clearance of [11C]-palmitate from the myocardium, an index of NEFA beta-oxidation, was similar between the groups (half-times of activity 17.6 +/- 1.6 vs 19.5 +/- 2.3 min, respectively, NS) CONCLUSION/INTERPRETATION: The results indicate that myocardial NEFA uptake and beta-oxidation are not altered in patients with IGT. Thus, it is not likely that altered NEFA metabolism contributes to the deterioration of the cardiac function in patients with IGT or Type II diabetes.

Occurrence and predictors of retinopathy and visual acuity in Type 2 diabetic patients and control subjects. 10-year follow-up from the diagnosis.

The evolution of visual acuity and retinopathy and their risk factors in patients with newly diagnosed type 2 diabetes and in control subjects. A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82 women) non-diabetic control subjects recruited from the population register. The frequency of retinopathy was determined by grading of 45 degrees fundus photographs at baseline and after 5 and 10 years. By the 10-year follow-up the diabetic patients had lower visual acuity than the control subjects. The impairment of the visual acuity correlated inversely to HbA(1C) value of the 5-year examination. The frequency of retinopathy in type 2 diabetic patients increased sharply after 5 years and at 10-year 55% of diabetic patients had signs of retinopathy. The frequency of retinopathy in the control subjects was low, but detectable. In the diabetic patients poor glycemic control was the most important predictive factor for the development of retinopathy. In the control subjects blood pressure levels were higher and microalbuminuria more common in those with than in those without retinopathy. The visual acuity deteriorated and the frequency of retinopathy increased in newly diagnosed type 2 diabetic patients with duration of disease and poor glycemic control. Interestingly, higher blood pressure levels and microalbuminuria predicted retinopathy in control subjects.

APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose.

BACKGROUND: The E4 allele of the apolipoprotein gene (APOE) is associated with a greater serum cholesterol response to dietary changes in fat and cholesterol. However, less is known about the interaction between APOE polymorphism and other macronutrients in the diet. OBJECTIVE: We evaluated the interaction between APOE polymorphism and dietary fat and carbohydrate, particularly sucrose, in relation to serum lipid concentrations. DESIGN: A total of 284 men and 130 women with coronary artery disease (mean age: 61 y; range: 33-74 y) participated in the cross-sectional EUROASPIRE study. Serum lipids and fatty acids in cholesteryl esters (CEs) were measured and APOE genotypes were determined. Dietary intake was examined by using a 4-d food record. RESULTS: Patients were grouped by APOE genotype: E2 (E2/E2 and E2/E3; n = 21), E3 (E3/E3; n = 245), and E4 (E4/E2, E4/E3, and E4/E4; n = 148). Patients with the E2 allele had lower LDL-cholesterol concentrations and tended to have higher triacylglycerol concentrations than did patients with the E3 or E4 allele; concentrations were not significantly different between the last 2 groups. In regression analysis, significant predictors of serum triacylglycerol were the interaction between sucrose intake and the E2 allele, proportion of n-3 fatty acids in CEs, body mass index, and diabetes. A high sucrose intake was associated with high triacylglycerol concentrations only in patients with the E2 allele. Interaction between saturated fat intake and the E2 allele, proportion of linoleic acid in CEs, and fiber intake predicted serum cholesterol. CONCLUSION: Coronary artery disease patients with the E2 allele will likely have a greater triacylglycerol response to high dietary sucrose intakes than will patients with the E3 or E4 allele.