Nutritional impacts of a fruit and vegetable subsidy programme for disadvantaged Australian Aboriginal children.

Healthy food subsidy programmes have not been widely implemented in high-income countries apart from the USA and the UK. There is, however, interest being expressed in the potential of healthy food subsidies to complement nutrition promotion initiatives and reduce the social disparities in healthy eating. Herein, we describe the impact of a fruit and vegetable (F&V) subsidy programme on the nutritional status of a cohort of disadvantaged Aboriginal children living in rural Australia. A before-and-after study was used to assess the nutritional impact in 174 children whose families received weekly boxes of subsidised F&V organised through three Aboriginal medical services. The nutritional impact was assessed by comparing 24 h dietary recalls and plasma carotenoid and vitamin C levels at baseline and after 12 months. A general linear model was used to assess the changes in biomarker levels and dietary intake, controlled for age, sex, community and baseline levels. Baseline assessment in 149 children showed low F&V consumption. Significant increases (P< 0.05) in ß-cryptoxanthin (28.9 nmol/l, 18%), vitamin C (10.1 µmol/l, 21%) and lutein-zeaxanthin (39.3 nmol/l, 11%) levels were observed at the 12-month follow-up in 115 children, although the self-reported F&V intake was unchanged. The improvements in the levels of biomarkers of F&V intake demonstrated in the present study are consistent with increased F&V intake. Such dietary improvements, if sustained, could reduce non-communicable disease rates. A controlled study of healthy food subsidies, together with an economic analysis, would facilitate a thorough assessment of the costs and benefits of subsidising healthy foods for disadvantaged Aboriginal Australians.

Independent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes.

BACKGROUND AND AIM: Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data. METHODS: Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae. RESULTS: Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.

Estimated insulin sensitivity in Type 1 diabetes adults using clinical and research biomarkers.

AIMS: Insulin resistance in people with type 1 diabetes (T1D) is associated with increased risk of chronic complications and death. The gold standard to quantify insulin sensitivity, a euglycaemic hyperinsulinaemic clamp, is not applicable to clinical practice. We have employed clamp studies to develop a panel of formulae to estimate insulin sensitivity in adults with T1D for use in clinical practice and trials. METHODS: Clamps were conducted in 28 adults with T1D, who were also characterised with 38 clinical and research biomarkers. Exhaustive search analysis was used to derive equations correlating with clamp-quantified glucose disposal rate (GDR), GDR/plasma insulin (M/I) and log10M/I. RESULTS: Measured insulin sensitivity correlated with BMI, WHR, HDL-C, adipokines and inflammation markers on univariate analysis. Exhaustive search analysis derived three formulae correlating with clamp-derived GDR and logM/I (p < 0.0001), accounting for ≈62% of their variability. A formula using gender, age, HDL-C, pulse pressure and WHR performed as well as those containing inflammation and adipokine measures. CONCLUSIONS: The performance of formulae using routinely available parameters with/without research biomarkers in clinical studies and trials, particularly related to future complications, relevant lifestyle interventions, insulin delivery modes and insulin sensitisers is merited.

Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes mellitus.

OBJECTIVES: Circulating low molecular weight (<10 kDa) fluorophores (LMW-F) measured by non-specific fluorescence spectroscopy may detect small advanced glycation end-products (AGEs) not recognized by other assays. This longitudinal study assessed correlates of LMW-F and predictive power of LMW-F levels for vascular health in Type 1 diabetes (T1DM) patients. METHODS: Fasting patients with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/-15 months). LMW-F levels were also measured once in 112 healthy control subjects. RESULTS: Relative to controls, LMW-F levels were higher in diabetic subjects at initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02). Rises in LMW-F levels in individual diabetic subjects correlated significantly with worsening renal function (BUN), glycemia (HbA1c) and with vascular dysfunction (systemic vascular resistance). CONCLUSIONS: LMW-F levels predict levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM reflect variations in glycemia and renal function. Biochemical characterization of LMW-F would facilitate understanding of the potential utility of LMW-F as a therapeutic target.

Plasma semicarbazide-sensitive amine oxidase activity in type 1 diabetes is related to vascular and renal function but not to glycaemia.

PURPOSE: Associations of semicarbazide-sensitive amine oxidase (SSAO) activity with renal and vascular function, oxidative stress, glycaemia and diabetes complications were determined. METHODS: Plasma SSAO activity in 94 type 1 diabetes (T1DM) patients, including 34 with microvascular complications T1DM CX[+], and in 96 healthy subjects (CON) was measured by production of benzaldehyde using high-performance liquid chromatography (HPLC). RESULTS: SSAO activity (mean ± SD) was greater in T1DM than in CON (1049 ± 294 vs 749 ± 204 mU/L; p < 0.00001) and was higher in T1DM CX[+] vs complication-free DM subjects (1148 ± 313 mU/L vs 982 ± 269 mU/L; p = 0.01). In T1DM, SSAO activity correlated with renal dysfunction [estimated glomerular filtration rate (eGFR): r = -0.44; p = 0.0001; cystatin C: r = 0.47; p = 0.0001] and markers of inflammation [soluble vascular cell adhesion molecule-1 (sVCAM-1): r = 0.41, p = 0.0001; soluble intercellular adhesion molecule-1 (sICAM-1): r = 0.33, p = 0.002] and was inversely related to small artery elasticity (SAE) (r = -0.23, p = 0.03). In CON, SSAO activity correlated with HbA1c (r = 0.26; p = 0.02). CONCLUSION: In T1DM, SSAO activity correlates with renal dysfunction, but not with glycaemia, and may promote vascular inflammation and be a therapeutic target.

Thioflavin T fluorescence in human serum: correlations with vascular health and cardiovascular risk factors.

OBJECTIVES: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. DESIGN, METHODS, AND RESULTS: Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the combined data set showed significant inverse correlation (p=0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. CONCLUSIONS: We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.

Increased serum kallistatin levels in type 1 diabetes patients with vascular complications.

BACKGROUND: Kallistatin, a serpin widely produced throughout the body, has vasodilatory, anti-angiogenic, anti-oxidant, and anti-inflammatory effects. Effects of diabetes and its vascular complications on serum kallistatin levels are unknown. METHODS: Serum kallistatin was quantified by ELISA in a cross-sectional study of 116 Type 1 diabetic patients (including 50 with and 66 without complications) and 29 non-diabetic controls, and related to clinical status and measures of oxidative stress and inflammation. RESULTS: Kallistatin levels (mean(SD)) were increased in diabetic vs. control subjects (12.6(4.2) vs. 10.3(2.8) µg/ml, p = 0.007), and differed between diabetic patients with complications (13.4(4.9) µg/ml), complication-free patients (12.1(3.7) µg/ml), and controls; ANOVA, p = 0.007. Levels were higher in diabetic patients with complications vs. controls, p = 0.01, but did not differ between complication-free diabetic patients and controls, p > 0.05. On univariate analyses, in diabetes, kallistatin correlated with renal dysfunction (cystatin C, r = 0.28, p = 0.004; urinary albumin/creatinine, r = 0.34, p = 0.001; serum creatinine, r = 0.23, p = 0.01; serum urea, r = 0.33, p = 0.001; GFR, r = -0.25, p = 0.009), total cholesterol (r = 0.28, p = 0.004); LDL-cholesterol (r = 0.21, p = 0.03); gamma-glutamyltransferase (GGT) (r = 0.27, p = 0.04), and small artery elasticity, r = -0.23, p = 0.02, but not with HbA1c, other lipids, oxidative stress or inflammation. In diabetes, geometric mean (95%CI) kallistatin levels adjusted for covariates, including renal dysfunction, were higher in those with vs. without hypertension (13.6 (12.3-14.9) vs. 11.8 (10.5-13.0) µg/ml, p = 0.03). Statistically independent determinants of kallistatin levels in diabetes were age, serum urea, total cholesterol, SAE and GGT, adjusted r2 = 0.24, p < 0.00001. CONCLUSIONS: Serum kallistatin levels are increased in Type 1 diabetic patients with microvascular complications and with hypertension, and correlate with renal and vascular dysfunction.

Systemic and vascular inflammation is elevated in early IgA and type 1 diabetic nephropathies and relates to vascular disease risk factors and renal function.

BACKGROUND: Inflammation is implicated in cardiovascular disease (CVD) and mortality in end-stage renal failure (ESRF). Its importance in early renal disease is yet to be defined. METHODS: Serum levels of systemic and vascular inflammatory markers in early IgA nephropathy (IgAN) and control subjects were measured and related to renal function and vascular risk factors. A parallel study in type 1 diabetes mellitus subjects with (T1DM Nx) and without nephropathy (T1DM No Nx) was performed. RESULTS: Fifty-one IgAN patients aged 46+/-2 years (mean+/-SEM), calculated creatinine clearance (CrCl) 88+/-5 ml/min, were compared with 51 matched control subjects. Forty-six T1DM Nx patients aged 40+/-2 years, CrCl 84+/-5 ml/min, and 73 T1DM No Nx patients aged 38+/-2 years were also compared. High sensitivity C-reactive protein (hsCRP) was elevated in IgAN, T1DM Nx and T1DM No Nx patients compared with controls [4.2+/-0.6 (P < 0.001), 4.1+/-0.6 (P < 0.001), 2.6+/-0.4 (P < 0.05) vs 1.6+/-0.3 mg/l]. Levels in T1DM Nx patients were higher than in T1DM No Nx patients (P < 0.05). Inflammation and vascular dysfunction as measured by pulse pressure (PP) were related. HsCRP correlated with PP in IgAN and T1DM Nx (r = 0.47, P = 0.001; r = 0.40, P < 0.05). PP was the strongest independent predictor of hsCRP in IgAN (T = 2.45, P < 0.001), while body mass index (T = 7.83, P < 0.001) was the strongest predictor in T1DM Nx. Endothelial cell adhesion molecules were increased in T1DM Nx > IgAN > T1DM No Nx vs controls: soluble vascular adhesion molecule-1 (sVCAM-1) 760+/-30 (P < 0.001) > 663+/-34 (P = 0.001) > 601+/-21 (P < 0.05) vs 536+/-15 ng/ml; soluble intracellular adhesion molecule-1 (sICAM-1) 320+/-8 (P < 0.001) > 313+/-13 (P < 0.001) > 307+/-8 (P < 0.001) vs 244+/-6 ng/ml. sVCAM-1 levels were higher in T1DM Nx than in T1DM No Nx, P < 0.001. In IgAN and T1DM Nx, hsCRP correlated with sICAM-1 (r = 0.33, P = 0.017; r = 0.37; P = 0.017). sVCAM-1 was related to renal function in IgAN and T1DM Nx: serum cystatin C (r = 0.63, P < 0.001: r = 0.425, P = 0.002), and urine protein:creatinine ratio in IgAN (r = 0.48; P = 0.001). CONCLUSIONS: Systemic and vascular markers of inflammation are increased in early renal disease and relate to renal dysfunction and cardiovascular risk factors. Inflammation may be a common process in various renal diseases and may link and accelerate renal dysfunction and CVD.