Using the AUSDRISK score to screen for pre-diabetes and diabetes in GP practices: a case-finding approach.

OBJECTIVE: To identify the optimal AUSDRISK threshold score to screen for pre-diabetes and diabetes. METHODS: A total of 406 adult patients not diagnosed with diabetes were screened in General Practices (GP) between May and October 2019. All patients received a point of care (POC) HbA1c test. HbA1c test results were categorised into diabetes (≥6.5% or ≥48 mmol/mol), pre-diabetes (5.7-6.4% or 39-47 mmol/mol), or normal (<5.7% or 39 mmol/mol). RESULTS: Of these patients, 9 (2%) had undiagnosed diabetes and 60 (15%) had pre-diabetes. A Receiver Operator Characteristic (ROC) curve was constructed to predict the presence of pre-diabetes and diabetes; the area under the ROC curve was 0.72 (95%CI 0.65-0.78) indicating modest predictive ability. The optimal threshold cut point for AUSDRISK score was 17 (sensitivity 76%, specificity 61%, + likelihood ratio (LR) 1.96, - likelihood ratio of 0.39) while the accepted cut point of 12 performed less well (sensitivity 94%, specificity 23%, +LR=1.22 -LR+0.26). CONCLUSIONS: The AUSDRISK tool has the potential to be used as a screening tool for pre-diabetes/diabetes in GP practices. A cut point of ≥17 would potentially identify 75% of all people at risk and three in 10 sent for further testing would be positive for prediabetes or diabetes. IMPLICATIONS FOR PUBLIC HEALTH: Routine case-finding in high-risk patients will enable GPs to intervene early and prevent further public health burden from the sequelae of diabetes.

Association between dietary zinc intake and mortality among Chinese adults: findings from 10-year follow-up in the Jiangsu Nutrition Study.

PURPOSE: Population studies of the association between zinc intake and mortality yield inconsistent findings. Using data from Jiangsu Nutrition Study, we aimed to assess the association between zinc intake and mortality among Chinese adults. METHODS: We prospectively studied 2832 adults aged 20 years and older with a mean follow-up of 9.8 years. At baseline, food intake was measured by 3-day weighed food record (WFR) between September and December in 2002. Death occurrence was assessed in 2012 during a household visit as well as by data linkage with the regional death registry. Hazard ratios (HRs) and 95% CI were calculated using competing risks regression (CVD and cancer mortality) and Cox proportional hazards analysis (all-cause mortality). RESULTS: During 27,742 person-years of follow-up, there were 184 deaths [63 cancer deaths and 70 cardiovascular disease (CVD) deaths]. Dietary zinc to energy ratio was positively associated with cancer and all-cause mortality. Across quartiles of the zinc to energy ratio from low to high, the HR (95% CI) for all-cause mortality was 1.00, 1.80 (95% CI 1.10-2.95), 1.55 (95% CI 0.96-2.50), and 1.85 (95% CI 1.11-3.07), respectively. Comparing the extreme quartiles of the zinc to energy ratio, the HR for cancer mortality was 2.28 (95% CI 1.03-5.04). CONCLUSION: Zinc intake was positively related to all-cause mortality and cancer mortality.

TNF-α gene expression is increased following zinc supplementation in type 2 diabetes mellitus.

Chronic low-grade inflammation in type 2 diabetes mellitus (DM) can elicit changes in whole-body zinc metabolism. The interaction among the expression of inflammatory cytokines, zinc transporter and metallothionein (MT) genes in peripheral blood mononuclear cells in type 2 DM remains unclear. In a 12-week randomized controlled trial, the effects of zinc (40 mg/day) supplementation on the gene expression of cytokines, zinc transporters and MT in women with type 2 DM were examined. In the zinc-supplemented group, gene expression of tumour necrosis factor (TNF)-α tended to be upregulated by 27 ± 10 % at week 12 compared to baseline (P = 0.053). TNF-α fold change in the zinc-treated group was higher than in those without zinc supplementation (P < 0.05). No significant changes were observed in the expression or fold change of interleukin (IL)-1ß or IL-6. Numerous bivariate relationships were observed between the fold changes of cytokines and zinc transporters, including ZnT7 with IL-1ß (P < 0.01), IL-6 (P < 0.01) and TNF-α (P < 0.01). In multiple regression analysis, IL-1ß expression was predicted by the expression of all zinc transporters and MT measured at baseline (r (2) = 0.495, P < 0.05) and at week 12 (r (2) = 0.532, P < 0.03). The current study presents preliminary evidence that zinc supplementation increases cytokine gene expression in type 2 DM. The relationships found among zinc transporters, MT and cytokines suggest close  interactions between zinc homeostasis and inflammation.

Micronutrient status in female university students: iron, zinc, copper, selenium, vitamin B12 and folate.

Young women are at an increased risk of micronutrient deficiencies, particularly due to higher micronutrient requirements during childbearing years and multiple food group avoidances. The objective of this study was to investigate biomarkers of particular micronutrients in apparently healthy young women. Female students (n = 308; age range 18-35 year; Body Mass Index 21.5 ± 2.8 kg/m2; mean ± SD) were recruited to participate in a cross-sectional study. Blood samples were obtained from participants in the fasted state and analysed for biomarkers of iron status, vitamin B12, folate, homocysteine, selenium, zinc, and copper. The results show iron deficiency anaemia, unspecified anaemia, and hypoferritinemia in 3%, 7% and 33.9% of participants, respectively. Low vitamin B12 concentrations (<120 pmol/L) were found in 11.3% of participants, while 4.7% showed sub-clinical deficiency based on serum methylmalonic acid concentrations >0.34 µmol/L. Folate concentrations below the reference range were observed in 1.7% (serum) or 1% (erythrocytes) of participants, and 99.7% of the participant had erythrocyte-folate concentrations >300 nmol/L. Serum zinc concentrations <10.7 µmol/L were observed in 2% of participants. Serum copper and selenium concentrations were below the reference range in 23% and 11% of participants, respectively. Micronutrient deficiencies including iron and vitamin B12, and apparent excess of folate are present in educated Australian female students of childbearing age, including those studying nutrition. The effects of dietary behaviours and food choices on markers of micronutrient status require further investigation.

Inflammation markers predict zinc transporter gene expression in women with type 2 diabetes mellitus.

The pathology of type 2 diabetes mellitus (DM) often is associated with underlying states of conditioned zinc deficiency and chronic inflammation. Zinc and omega-3 polyunsaturated fatty acids each exhibit anti-inflammatory effects and may be of therapeutic benefit in the disease. The present randomized, double-blind, placebo-controlled, 12-week trial was designed to investigate the effects of zinc (40 mg/day) and α-linolenic acid (ALA; 2 g/day flaxseed oil) supplementation on markers of inflammation [interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP)] and zinc transporter and metallothionein gene expression in 48 postmenopausal women with type 2 DM. No significant effects of zinc or ALA supplementation were observed on inflammatory marker concentrations or fold change in zinc transporter and metallothionein gene expression. Significant increases in plasma zinc concentrations were observed over time in the groups supplemented with zinc alone or combined with ALA (P=.007 and P=.009, respectively). An impact of zinc treatment on zinc transporter gene expression was found; ZnT5 was positively correlated with Zip3 mRNA (P<.001) only in participants receiving zinc, while zinc supplementation abolished the relationship between ZnT5 and Zip10. IL-6 predicted the expression levels and CRP predicted the fold change of the ZnT5, ZnT7, Zip1, Zip7 and Zip10 mRNA cluster (P<.001 and P=.031, respectively). Fold change in the expression of metallothionein mRNA was predicted by TNF-α (P=.022). Associations among inflammatory cytokines and zinc transporter and metallothionein gene expression support an interrelationship between zinc homeostasis and inflammation in type 2 DM.

Iron supplementation decreases plasma zinc but has no effect on plasma fatty acids in non-anemic women.

Limited information is available on the role of iron in fatty acid metabolism in humans. We hypothesized that iron supplementation will increase desaturase activity, and so, the aim of this study was to determine the effect of iron supplementation on fatty acid desaturase activity in young women. Participants were randomly assigned to a control group (CG) or supplementation group (SG) who were provided with 37.4 mg of elemental iron daily for 12 weeks. Forty women completed the trial, n = 19 in CG and n = 21 in SG. The mean ages were 25.2 and 24.6 years, and body mass indices were 21.8 and 21.2 (kg/m(2)) in CG and SG, respectively. Serum ferritin concentrations increased significantly (P < .01) in subjects assigned to SG but were unchanged in CG. Serum iron concentrations were not significantly changed. Plasma zinc concentrations at the end of the intervention were similar to baseline values for individuals in CG but were decreased significantly (P = .004) in SG. Plasma fatty acids, phospholipid fatty acids, and desaturase activities, expressed as precursor-to-product ratios, were not significantly affected by the intervention, although in SG the concentration of serum ferritin was correlated positively (P < .05) with Δ6-desaturase activity. Supplementing non-anemic women with low dose iron improves iron status but has no significant effect on desaturase activity. The lack of a clear effect on an indirect indicator of desaturase activity may be related to the antagonism between iron and zinc, as illustrated by the decrease in plasma zinc concentrations in women who were supplemented with iron.

A randomized controlled trial in young women of the effects of consuming pork meat or iron supplements on nutritional status and feeling of well-being.

OBJECTIVES: Limited information is available on the role of pork meat in influencing iron status. The aim of this study was to determine the effect of consuming pork meat as compared to iron supplementation on nutritional status and feeling of well-being. METHODS: Young women were randomly assigned to a control diet (CG), a pork-containing diet (PG), or a control diet with iron supplementation (SG) for 12 weeks. Sixty-five women aged 24.6 ± 4.4 years (mean ± SD) completed the trial. RESULTS: Serum ferritin concentrations were increased significantly (p = 0.001) in participants assigned to the SG as compared with the other groups, as assessed by repeated-measures analysis of variance. At week 12, hemoglobin concentrations were significantly higher in PG and SG as compared with CG. Plasma zinc concentrations at the end of the intervention were similar to baseline concentrations for individuals in the CG and PG but were decreased significantly (p < 0.05) in SG. Plasma-, erythrocyte-folate, and serum vitamin B6 and B12 concentrations were not significantly affected by the intervention, although the concentrations of vitamins B6 and B12 tended to increase in PG. Well-being, as measured using the Health Survey Short Form (SF-36) and its 8 multi-item scales, showed significant improvement in vitality in SG (p < 0.05) and bodily pain in PG (p < 0.05). No significant relationships were observed between these health concept scores and biomarkers of nutritional status. CONCLUSIONS: Consumption of pork meat by young women maintains hemoglobin levels to the same extent as low-dose iron supplementation and enhances the components of well-being, mainly their perception of bodily pain.

Zinc intake and its dietary sources: results of the 2007 Australian National Children's Nutrition and Physical Activity Survey.

The current Australian Nutrient Reference Values (NRV) use different Estimated Average Requirements (EAR) for zinc for adolescent boys and girls compared to the previous recommendations. The adequacy of zinc intakes of 2-16 years old children (n = 4834) was examined in the 2007 Australian National Children's Nutrition and Physical Activity Survey. Zinc intakes were estimated from two 24-h recalls and compared with age- and gender-specific NRV. Food sources of zinc were assessed and compared with those of the 1995 National Nutrition Survey. The mean (SD) zinc intake was 10.2 (3.0) mg/day for all children. Nearly all children met the EAR for zinc except for 14-16 years old boys (29% did not meet EAR). Children (2-3 years) were at highest risk of excessive zinc intakes with 79% exceeding the Upper Level of Intake. Meat and poultry; milk products; and cereals and cereal products contributed 68% of total zinc intake. The contribution of cereals to total zinc intake has increased significantly since 1995, due to the greater market-availability of zinc-fortified breakfast cereals. We conclude that sub-groups of Australian children are at-risk of inadequate (boys 14-16 years) or excessive (children 2-3 years) zinc intakes, and monitoring of zinc status is required.

Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease.

In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1ß, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

Relative and biomarker-based validity of a food frequency questionnaire that measures the intakes of vitamin B(12), folate, iron, and zinc in young women.

Folate, vitamin B(12), iron, and zinc are particularly important nutrients for women of childbearing age. We tested the hypothesis that an electronic, 235-item, semiquantitative food frequency questionnaire (FFQ) is a valid measure of dietary intake when compared with repeat dietary 24-hour recalls. Biomarkers of folate, vitamin B(12), iron, and zinc were determined because their measurement errors are unrelated to errors in dietary questionnaires. Female adults (N = 256) aged 18 to 35 years completed the FFQ, and a representative subset (n = 53) completed repeat dietary 24-hour recalls. The FFQ estimates (mean ± SD) were 315 ± 132 µg for folate, 3.1 ± 2.1 µg for vitamin B(12), 15.4 ± 5.6 mg for iron, and 15.1 ± 6.4 mg for zinc. The percentage of women classified within the same ±1 quartile for energy intake by the 2 methods was 77.3%. There was moderate agreement between the 2 dietary methods, and no systematic bias was noted for energy, folate, vitamin B(12), and zinc. The deattenuated energy-adjusted correlation coefficients ranged from 0.41 (dietary folate equivalents) to 0.60 (folate). Significant correlations between biomarker and nutrient intakes were found for folate (r = 0.37, P < .01) and vitamin B(12) (r = 0.27, P < .01). The electronic FFQ developed in the present study is a relatively valid tool that was able to adequately assess and rank individuals according to their nutrient intakes.

Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus.

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3'-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

Vitamin B12 in health and disease.

Vitamin B(12) is essential for DNA synthesis and for cellular energy production.This review aims to outline the metabolism of vitamin B(12), and to evaluate the causes and consequences of sub-clinical vitamin B(12) deficiency. Vitamin B(12) deficiency is common, mainly due to limited dietary intake of animal foods or malabsorption of the vitamin. Vegetarians are at risk of vitamin B(12) deficiency as are other groups with low intakes of animal foods or those with restrictive dietary patterns. Malabsorption of vitamin B(12) is most commonly seen in the elderly, secondary to gastric achlorhydria. The symptoms of sub-clinical deficiency are subtle and often not recognized. The long-term consequences of sub-clinical deficiency are not fully known but may include adverse effects on pregnancy outcomes, vascular, cognitive, bone and eye health.

The effect of zinc supplementation in humans on plasma lipids, antioxidant status and thrombogenesis.

The potential exists for zinc to influence numerous metabolic functions and to impact a range of diseases. In the present review we examine the reported relationships between zinc and plasma lipids, haemostasis and other factors postulated to play a role in atherogenesis. Ecological studies that investigated zinc intake or status, and incidence of coronary heart disease (CHD) reveal no consistent pattern. The conflicting observations may be explained by differences in the extent of CHD, site of atherosclerosis, or confounding factors. In most studies the diurnal variation in serum zinc concentrations, and the lifestyle factors that affect cholesterol metabolism were not explicitly considered. Results of randomised controlled trials show that low-density lipoprotein (LDL) oxidation and the concentrations of LDL-cholesterol (c), total cholesterol and triglycerides in plasma are unaffected by supplementation with up to 150 mg Zn/d. In contrast, plasma high-density lipoprotein (HDL)-c concentrations decline when zinc supplements provide a dose >50 mg/d. Limited data suggest that sustained hyperzincaemia predisposes individuals to thrombogenesis, whereas acute zinc depletion impairs platelet aggregation and prolongs bleeding time. In addition, Zinc supplements have been shown in some studies to decrease Cu/Zn-superoxide dismutase activity, primarily due to the antagonistic relationship between high zinc intakes and copper absorption. Besides the demonstrated adverse effect of zinc supplementation on plasma HDL-c concentrations in apparently healthy men, there is insufficient evidence to determine the role of zinc supplementation in influencing other risk factors for CHD such as antioxidant status and thrombogenesis.

Antioxidant properties of palm fruit extracts.

Phenolic compounds have been shown to exhibit bioactive properties, and in particular antioxidant effects. A phenolic-rich fraction has been isolated from the aqueous by-product obtained during the milling of oil palm fruits. The objectives of the study were to determine the phenolic content of the crude and ethanolic extracts of oil palm fruits and to evaluate the antioxidant properties of these extracts. The total phenolics content of the crude and ethanol extracts as determined by the Folin-Ciocalteu method were found to be 40.3 +/- 0.5 and 49.6 +/- 0.6 mg GAE/g extract (dry basis), respectively. The radical scavenging activity of the extracts determined using 2,2 diphenyl-1-picrylhydrazyl radical (DPPH.) indicated that both crude and ethanol extracts exhibit hydrogen-donating capacity, and have antiradical power (ARP) comparable to ascorbic acid. The DPPH radical scavenging activity of the extracts were less than that of gallic acid, but the time-course variations of the scavenging curves suggest that the extracts acted by a mechanism similar to that of gallic acid. The electron-donating potentials of the extracts were inferred from the hydrogen peroxide scavenging and reducing power assays. The reducing power of crude and ethanol extracts at 1 mM GAE were found to be comparable to that of 0.3 mM gallic acid. The extracts indicated complete scavenging of hydrogen peroxide at concentrations above 0.4 mM GAE. These findings suggest that the crude and ethanol extracts are able to scavenge free radicals, by either hydrogen or electron donating mechanisms, and can therefore act as primary antioxidants.

A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men.

Fruit and vegetable consumption is inversely associated with coronary heart disease (CHD) risk. The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status. We assessed CHD risk by measuring the concentrations of homocysteine, lipids, lipoproteins, glucose and insulin. Men were recruited to participate in a randomized double-blind, crossover trial with 2 periods of 6 wk, separated by a 3-wk wash-out period. Supplementation with the encapsulated mixed extract (Juice Plus) was compared with physically similar placebo capsules. Thirty-two men (13 smokers, 19 nonsmokers) completed the study with a mean compliance of 88%. Compared with placebo, supplementation increased the concentrations of plasma beta-carotene (0.24 +/- 0.15 vs. 1.12 +/- 0.70 micro mol/L; mean +/- SD; P < 0.0001), retinol (1.87 +/- 0.33 vs. 2.00 +/- 0.43 micro mol/L; P < 0.05), alpha-tocopherol (16.8 +/- 7.3 vs. 19.3 +/- 6.8 micro mol/L; P < 0.01), ascorbic acid (72.1 +/- 19.4 vs. 84.1 +/- 13.5 micro mol/L; P < 0.002) and folic acid (24.5 +/- 10.0 vs. 44.9 +/- 16.9 nmol/L; P < 0.0001). Plasma homocysteine was reduced (8.2 +/- 1.5 vs. 7.6 +/- 1.1; P < 0.05) and inversely related (r = -0.40, P < 0.001) with serum folate concentrations. Plasma vitamin C was positively correlated with the resistance of LDL to oxidation (r = 0.26, P < 0.05) and the plasma ferric reducing/antioxidant power (FRAP) tended to be greater after supplementation than after the placebo period (1125.5 +/- 144.1 vs. 1180.3 +/- 158.1 micro mol/L; P < 0.065). Plasma glucose, insulin and lipid concentrations were unaffected. Responses of smokers and nonsmokers did not differ. In the absence of dietary modification, supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk.