Nanomaterials by design: a review of nanoscale metallic multilayers.

Nanoscale metallic multilayers have been shown to have a wide range of outstanding properties, which differ to a great extent from those observed in monolithic films. Their exceptional properties are mainly associated with the large number of interfaces and the nanoscale layer thicknesses. Many studies have investigated these materials focusing on magnetic, mechanical, optical, or radiation tolerance properties. Thus, this review provides a summary of the findings in each area, including a description of the general attributes, the adopted synthesis methods and most common characterization techniques used. This information is followed by a compendium of the material properties and a brief discussion of related experimental data, as well as existing and promising applications. Other phenomena of interest, including thermal stability studies, self-propagating reactions and the progression from nano multilayers to amorphous and/or crystalline alloys, are also covered. In general, this review highlights the use of nano multilayer architectures as viable routes to overcome the challenges of designing and implementing new engineering materials at the nanoscale.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Dietary inflammatory index or Mediterranean diet score as risk factors for total and cardiovascular mortality.

BACKGROUND AND AIMS: Dietary patterns are associated with risk of cardiovascular disease (CVD). We aimed to examine associations of the Dietary Inflammatory Index (DII) and the Mediterranean Diet Score (MDS) with total, cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in the Melbourne Collaborative Cohort Study; and compare the strengths of the associations. METHODS AND RESULTS: In our prospective cohort study of 41,513 men and women aged 40-69 years, a food frequency questionnaire was completed at baseline and mortality data were obtained via linkage with local and national registries over an average of 19 years follow up. At baseline, questionnaires were completed and physical measures and blood samples taken. Cox proportional hazards models, adjusting for age, alcohol consumption, sex, region of origin, personal history of CVD or diabetes and family history of CVD, were used to assess associations between dietary scores and mortality. More Mediterranean or less inflammatory diets were associated with lower total, CVD and CHD mortality. The hazard ratio for total mortality comparing the highest and lowest quintiles was 1.16 (95%CI: 1.08-1.24) for DII; and 0.86 (95%CI: 0.80-0.93) comparing the highest and lowest three categories of MDS. Using the Bayesian information criterion, there was no evidence that the DII score was more strongly associated with total and CVD mortality than was the MDS. CONCLUSIONS: The MDI and the DII show similar associations with total and cardiovascular mortality, consistent with the consensus that plant-based diets are beneficial for health.

Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

Age-related macular degeneration and mortality: the Melbourne Collaborative Cohort Study.

AimsTo assess associations between features of age-related macular degeneration (AMD) and mortality.MethodsA total of 21 129 participants from the Melbourne Collaborative Cohort Study aged 47-85 years (60% female) were assessed for AMD (2003-2007). Mortality data to December 31, 2012 were obtained through linkage with the National Death Index. Associations were assessed using Cox regression, adjusting for age, sex, smoking, region of birth, education, physical activity, diet and alcohol.ResultsLate AMD was identified in 122 (0.6%) participants, including those with choroidal neovascularisation (n=55, 0.3%), geographic atrophy (n=87, 0.4%) and reticular pseudodrusen (n=87, 0.4%). After a median follow-up period of 8.1 years, 1669 (8%) participants had died, including those from cardiovascular diseases (386), tobacco-related cancers (179), and neurodegenerative disease (157). There was evidence of an increased rate of all-cause mortality for those with choroidal neovascularisation (Hazard Ratio (HR) 1.71 95% CI 1.06-2.76) and geographic atrophy (HR 1.46 95% CI 0.99-2.16). Choroidal neovascularisation was also associated with an increased rate of cardiovascular mortality (HR 3.16 95% CI 1.62-6.15) and geographic atrophy was associated with an increased rate of death from tobacco-related cancer (HR 2.86 95% CI 1.15-7.09). Weak evidence was also present for an association between choroidal neovascularisation and death from neurodegenerative disease (HR 2.49 95% CI 0.79-7.85). Neither reticular pseudodrusen nor the earlier stages of AMD were associated with mortality.ConclusionsLate AMD is associated with an increased rate of all-cause mortality. Choroidal neovascularisation and geographic atrophy were associated with death from cardiovascular disease and tobacco-related cancer, respectively.

The Emergent Literacy Skills of Preschool Children with Autism Spectrum Disorder.

A high percentage of school-age students with autism spectrum disorder (ASD) have reading comprehension difficulties leading to academic disadvantage. These difficulties may be related to differences in children's emergent literacy development in the preschool years. In this study, we examined the relationship between emergent literacy skills, broader cognitive and language ability, autism severity, and home literacy environment factors in 57 preschoolers with ASD. The children showed strengths in code-related emergent literacy skills such as alphabet knowledge, but significant difficulties with meaning-related emergent literacy skills. There was a significant relationship between meaning-related skills, autism severity, general oral language skills, and nonverbal cognition. Identification of these meaning-related precursors will guide the targets for early intervention to help ensure reading success for students with ASD.

Dietary inflammatory index, Mediterranean diet score, and lung cancer: a prospective study.

PURPOSE: To investigate prospectively the associations of Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) with lung cancer. METHODS: We used data from men and women aged 40-69 years at recruitment in 1990-1994, who were participants in the Melbourne Collaborative Cohort Study (n = 35,303). A total of 403 incident lung cancer cases were identified over an average 18-year follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors, with age as the time metric. RESULTS: An inverse correlation was observed between the DII and MDS (ρ = -0.45), consistent with a higher DII being pro-inflammatory and less 'healthy,' while a high MDS reflects a 'healthier' diet. The DII was positively associated with risk of lung cancer in current smokers [HRQ4 vs Q1 = 1.70 (1.02, 2.82); Ptrend = 0.008] (p interaction between DII quartiles and smoking status = 0.03). The MDS was inversely associated with lung cancer risk overall [HR7-9 vs 0-3 = 0.64 (0.45, 0.90); Ptrend = 0.005] and for current smokers (HR7-9 vs 0-3 = 0.38 (0.19, 0.75); Ptrend = 0.005) (p interaction between MDS categories and smoking status = 0.31). CONCLUSIONS: The MDS showed an inverse association with lung cancer risk, especially for current smokers. A high DII, indicating a more pro-inflammatory diet, was associated with risk of lung cancer only for current smokers. A healthy diet may reduce the risk of lung cancer, especially in smokers.

Note: A method for minimizing oxide formation during elevated temperature nanoindentation.

A standardized method to protect metallic samples and minimize oxide formation during elevated-temperature nanoindentation was adapted to a commercial instrument. Nanoindentation was performed on Al (100), Cu (100), and W (100) single crystals submerged in vacuum oil at 200 °C, while the surface morphology and oxidation was carefully monitored using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The results were compared to room temperature and 200 °C nanoindentation tests performed without oil, in order to evaluate the feasibility of using the oil as a protective medium. Extensive surface characterization demonstrated that this methodology is effective for nanoscale testing.

Dietary patterns as predictors of successful ageing.

OBJECTIVES: To examine associations between dietary patterns identified by factor analysis, and successful ageing. DESIGN: Prospective cohort study with diet measured in 1990-4, and successful ageing in 2003-7. Ordered logistic regression with outcome determined as dead/usual ageing/successful ageing was used to examine associations with quintile groups of dietary factor scores. PARTICIPANTS: Men and women (n=6308), without history of major illness at baseline, and aged >70 years at follow-up, or who had died before follow-up but would have been aged >70 at the commencement of follow-up, from the Melbourne Collaborative Cohort Study. MEASUREMENTS: Frequencies of intake of 121 foods at baseline were collected in a food frequency questionnaire. Anthropometry and other health and lifestyle data were collected. At follow-up, questionnaire data relating to mental health, physical function and medical history were used to define successful ageing. RESULTS: Four dietary factors were identified, characterized by higher loadings for (1) vegetables; (2) fruit, (3) feta, legumes, salad, olive oil, and inverse loadings for tea, margarine, cake, sweet biscuits and puddings; (4) meat, white bread, savoury pastry dishes and fried foods. In models excluding body size, the second factor 'Fruit' was positively associated with successful ageing (OR in top 20% vs lowest 20% of score 1.31, 95%CI (1.05-1.63), p trend across quintile groups 0.001); while the fourth factor 'Meat/fatty foods' was inversely associated (OR in top 20% vs lowest 20% of score 0.69, 95%CI (0.55-0.86), p trend across quintile groups 0.001). Factors 1 and 3 did not show significant associations with successful ageing. The association for 'Fruit' was little altered after adjustment for body size, while for 'Meat/fatty foods' the association was somewhat attenuated. CONCLUSION: A dietary pattern including plenty of fruit while limiting meat and fried foods may improve the likelihood of ageing successfully.

Elastic and viscoelastic characterization of agar.

Agar is a biological polymer, frequently used in tissue engineering research; due to its consistency, controllable size, and concentration-based properties, it often serves as a representative material for actual biological tissues. In this study, nanoindentation was used to characterize both the time-independent and time-dependent response of agar samples having various concentrations (0.5%-5.0% by weight). Quasi-static indentation was performed at different loads and depths using both open- and closed-loop controls. Reduced modulus (Er) values change with agar concentration, ranging from ∼30 kPa for 0.5% samples to ∼700 kPa for 5.0% samples, which is the same modulus range as usually encountered in soft biological materials. Dynamic indentation was performed to assess the effects of load, dynamic frequency and amplitude. Storage modulus values ranged from approximately 30 to 2300 kPa depending on agar concentration. Loss modulus remained consistently less than 30 kPa at all conditions, indicating a diminished damping response in agar.

Dietary intake of B vitamins and methionine and risk of lung cancer.

BACKGROUND/OBJECTIVES: B vitamins and related enzymes involved in one-carbon metabolism are necessary for DNA replication, DNA repair and regulation of gene expression. Disruption of one-carbon mechanism may affect cancer risk. We investigated prospectively the relationship between dietary intakes of methionine, B vitamins associated with one-carbon metabolism and risk of lung cancer. SUBJECTS/METHODS: The Melbourne Collaborative Cohort Study recruited 41,514 men and women aged 40-69 years between 1990 and 1994. During follow-up of 14,595 men and 22,451 women for an average of 15 years, we ascertained 348 incident lung cancers. Dietary intake of B vitamins and methionine was estimated from a 121-item food frequency questionnaire. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. RESULTS: In current smokers, dietary intake of riboflavin was inversely associated with lung cancer risk (HR=0.53; 95% CI: 0.29-0.94, fifth versus first quintile; P-linear trend=0.01). No associations were found for former or never smokers or for dietary intake of any of the other B vitamins or methionine. CONCLUSION: Overall, we found little evidence of an association between B vitamins or methionine and lung cancer risk. The weak inverse association between riboflavin and lung cancer risk in current smokers needs further investigation.

Does a Mediterranean diet reduce the mortality risk associated with diabetes: evidence from the Melbourne Collaborative Cohort Study.

BACKGROUND AND AIMS: Diabetes is a risk factor for cardiovascular disease (CVD), yet southern European migrants to Australia with high rates of type 2 diabetes have relatively low CVD mortality. Our aim was to determine whether a Mediterranean style diet could reduce mortality in people with diabetes. METHODS AND RESULTS: Participants included 16,610 males and 23,860 females from the Melbourne Collaborative Cohort Study; 25% were born in Greece or Italy, and 2150 had previously been diagnosed with diabetes or had elevated blood glucose at baseline (1990-94). Data on demographic, behavioral and physical risk factors were also collected. A personal Mediterranean Diet Score (MDS) was calculated using data from a validated 121-item food frequency questionnaire. Total and CVD mortality data were available up to 2003. Diabetes (new and known) at baseline, was associated with total mortality (men HR 1.43, 95%CI 1.26-1.62; women HR 1.86 95%CI 1.58-2.18), and CVD mortality (men HR 1.53, 95%CI 1.21-1.94; women HR 2.10 95%CI 1.48-2.97) in multivariate models. There was no evidence that glucose tolerance modified the associations between MDS and total or CVD mortality (p interaction all > 0.16). The HRs for total mortality per unit of MDS were 0.96 (95% CI 0.93-0.99) in men and 0.94 (95% CI 0.92-0.97) in women. The HRs for CVD mortality per unit of MDS were 0.94 (95% CI 0.89-0.99) in men and 0.94 (95% CI 0.87-1.01) in women. CONCLUSION: Our results add to the evidence supporting the benefit of a Mediterranean style diet for people with type 2 diabetes.

NMR-determined lipoprotein subclass profile is associated with dietary composition and body size.

BACKGROUND AND AIMS: Dyslipidemia is influenced by diet and body habitus. The Nuclear Magnetic Resonance spectroscopy lipoprotein subclass profile (NMR-LSP) is associated with diabetes and its vascular complications; and an NMR-LSP featuring large VLDL particles and small LDL and HDL particles is linked with cardiovascular disease (CVD). Thus interventions which favourably modify NMR-LSP may reduce risk for diabetes, its complications and CVD. The study aim was to investigate the associations between NMR-LSP, dietary composition and body size measures using data from the Melbourne Collaborative Cohort Study (MCCS). METHODS AND RESULTS: NMR-LSP was assessed in 313 men and 403 women (median age 54 years) randomly selected from a community-based cohort study. Diet was assessed using a specifically developed food frequency questionnaire (FFQ), and body size was assessed by body mass index (BMI) or waist:hips ratio (WHR). To simplify the 15 NMR-LSP variables, factor analysis was used to derive a single factor. Multivariate linear regression with this factor score as the dependent variable demonstrated that in men, total PUFA and n-6 dietary fat intake and BMI were associated with a more atherogenic NMR-LSP pattern; while in women dietary glycemic index and WHR demonstrated positive associations, and n-3 fat intake an inverse association. CONCLUSIONS: We developed a single factor score to summarize the NMR-LSP that has the benefit of combining all aspects of the NMR-LSP and accounting for correlations between them. We have shown correlations between the NMR-LSP and body size and dietary composition.

Effect of fatty acids on bone marrow lesions and knee cartilage in healthy, middle-aged subjects without clinical knee osteoarthritis.

OBJECTIVE: There is evidence that omega-3 polyunsaturated fatty acids alleviate the progression of osteoarthritis (OA). However, little work has been done to investigate the effect of fatty acids on bone marrow lesions and knee cartilage in healthy subjects. We examined this in a cohort of healthy middle-aged subjects without clinical knee OA. METHODS: Two hundred and ninety-three healthy adults without knee pain or injury were recruited from an existing community-based cohort. Intakes of fatty acids and food sources of these were estimated from a food frequency questionnaire at baseline. Tibial cartilage volume, tibial plateau bone area, tibiofemoral cartilage defects and bone marrow lesions were assessed approximately 10 years later using magnetic resonance imaging. RESULTS: In multivariate analyses, higher intakes of monounsaturated fatty acids (OR=2.14, 95% CI 1.04-4.39, P=0.04), total (OR=1.77, 95% CI 1.13-2.77, P=0.01) and n-6 polyunsaturated fatty acids (OR=1.69, 95% CI 1.10-2.61, P=0.02) were associated with an increased risk of bone marrow lesions. Intake of fatty acids was not significantly associated with cartilage volume or cartilage defects. CONCLUSION: These findings support the dietary recommendation towards a shift to foods rich in n-3 polyunsaturated fatty acids in order to maintain an optimal balance between dietary n-3 and n-6 polyunsaturated fatty acids, which is also important in the prevention of atherosclerosis. Although our findings will need to be confirmed in longitudinal studies, they suggest the potential of fatty acids to adversely effect the knee joint.

Alcohol intake, consumption pattern and beverage type, and the risk of Type 2 diabetes.

AIMS: To examine associations between amount and frequency of alcohol consumption, and Type 2 diabetes. METHODS: A prospective study of 36 527 adults aged 40-69 at baseline. Incident cases of Type 2 diabetes were identified by questionnaire 4 years later. Sex-specific logistic regression models, adjusting for country of birth, dietary glycaemic index, energy intake and age, and in a second model body mass index (BMI) and waist-hip ratio (WHR), were used. RESULTS: Diabetes status was ascertained for 31 422 (86%) participants, and 362 cases identified. Former drinkers had higher risks than lifetime abstainers. Female drinkers had lower risk than lifetime abstainers (ORs < 10 g/day 0.54, 95% CI 0.36-0.82; 10-19.9 g/day 0.57, 0.34-0.94; > or = 20 g/day 0.46, 0.24-0.88, P trend = 0.005). There was no relationship after adjustment for body size. For men, a weak inverse association was observed after adjustment for body size (ORs relative to lifetime abstainers: < 10 g/day 1.56, 0.95-2.55; 10-19.9 g/day 1.21, 0.69-2.10; 20-29.9 g/day 0.80, 0.40-1.60; = 30 g/day 0.86, 0.50-1.58, P trend = 0.036). Wine was the only beverage for which an inverse association was observed. Compared with men who did not drink in the week before baseline, men who drank > or = 210 g over 1-3 days had an increased risk of diabetes (OR 5.21, 1.79-15.19), while the same amount over more days did not increase risk. CONCLUSIONS: Total alcohol intake was associated with reduced risk only in women. Alcohol from wine was associated with reduced risk of Type 2 diabetes. A high daily intake of alcohol, even on only 1-3 days a week, may increase the risk of diabetes in men.

Leptin and other components of the Metabolic Syndrome in Mauritius--a factor analysis.

OBJECTIVE: To use factor analysis to examine the putative role of leptin in the Metabolic Syndrome, and to define better the associations among observed variables and the identified factors. DESIGN: Factor analysis of cross-sectional data from a 1987 survey. SUBJECTS: Non-diabetic residents of Mauritius who participated in population-based surveys in 1987 and 1992 (1414 men and 1654 women). MEASUREMENTS: Fasting and 2 h plasma glucose and insulin following a 75 g oral glucose load; seated blood pressure; body mass index (BMI); waist-to-hip ratio (WHR); and fasting serum triglycerides, HDL-cholesterol, leptin and uric acid concentrations. RESULTS: Principal components factor analysis revealed three factors for men and women that explained between 54 and 55% of the observed variance of the 12 measured variables. General features of these factors were as follows: factor 1, WHR, BMI, leptin, fasting and 2 h insulin, triglycerides, and HDL-cholesterol; factor 2, systolic and diastolic blood pressure, uric acid (men only), and fasting glucose (women only); and factor 3, fasting and 2 h glucose and insulin. Only three variables loaded on more than one factor with a loading > or = 0.4 (fasting and 2 h insulin, fasting glucose in women only). Leptin loaded on one factor only in both men and women. CONCLUSIONS: Since multiple factors underlie the Metabolic Syndrome, and since no observed variable loads on all three factors, more than one mechanism might account for the observed clustering of risk characteristics. Leptin does not unite features of this syndrome due to its loading on one factor only. Uric acid is related to a different factor in men and women. The absence of gender differences in factor loadings argues for similar mechanisms for the Metabolic Syndrome in men and women in Mauritius. International Journal of Obesity (2001) 25, 126-131

Impaired fasting glucose: how low should it go?

OBJECTIVE: Impaired fasting glucose (IFG) has been recently introduced as a stage of abnormal carbohydrate metabolism, but the evidence on which its glucose limits (fasting plasma glucose [FPG] 6.1-6.9 mmol/l) are based is not strong. The aim of this study was to determine if 6.1 mmol/l represents a clear cutoff in terms of the risk of future diabetes and in terms of elevated cardiovascular risk factor levels, and to examine the use of other lower limits of IFG. RESEARCH DESIGN AND METHODS: A population-based survey of the island of Mauritius was undertaken in 1987, with a follow-up survey 5 years later. On both occasions, an oral glucose tolerance test was performed and cardiovascular risk factors were measured. RESULTS: Data were available from 4,721 nondiabetic people at baseline, and from 3,542 at follow-up. At baseline, blood pressure, lipids, and obesity increased in a linear fashion with increasing FPG, with no evidence of a threshold effect. The risk of developing hypertension at follow-up was greater for those people with baseline FPG > or =6.1 mmol/l (P<0.001). The risk of developing diabetes at follow-up increased with increasing baseline FPG, but there was little evidence of a threshold near 6.1 mmol/l. CONCLUSIONS: Cardiovascular risk and risk of future diabetes increase continually with increasing FPG, and there is no threshold value on which to base a definition of IFG. If a lower limit of approximately 5.8 mmol/l is used, the category defines a group more similar to the group with impaired glucose tolerance, with regard to total prevalence and the risk of subsequent diabetes.