Validation of novel recipes for double-blind, placebo-controlled food challenges in children and adults.

BACKGROUND: In double-blind, placebo-controlled food challenges (DBPCFCs), the use of challenge materials in which blinding is validated is a prerequisite for obtaining true blinded conditions during the test procedure. Therefore, the aim of this study was to enlarge the available range of validated recipes for DBPCFCs to facilitate oral challenge tests in all age groups, including young children, while maximizing the top dose in an acceptable volume. METHODS: Recipes were developed and subsequently validated by a panel recruited by a matching sensory test. The best 30% of candidates were selected to participate in sensory testing using the paired comparison test. RESULTS: For young children, three recipes with cow's milk and one recipe with peanut could be validated which may be utilized in DBPCFCs. For children older than 4 years and adults, one recipe with egg, two with peanut, one with hazelnut, and one with cashew nut were validated for use in DBPCFCs. CONCLUSIONS: All recipes contained larger amounts of allergenic foods than previously validated. These recipes increase the range of validated recipes for use in DBPCFCs in adults and children.

A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients.

The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities, as well as on the ability of plasma to stimulate cellular cholesterol efflux. Twelve male type 1 diabetic patients with plasma cholesterol >5.0 mmol/L were studied while consuming their usual diet and after 6 weeks of a low-fat, low-cholesterol diet. Pre beta-HDL formation was measured using crossed immuno-electrophoresis. Plasma LCAT, CETP and PLTP activities were assayed by exogenous substrate methods. The ability of plasma to promote cellular cholesterol efflux out of Fu5AH rat hepatoma cells and out of human skin fibroblasts was also determined. Saturated fat intake was lowered (p = 0.001) due to replacement with carbohydrates, while mono- and polyunsaturated fat intake remained unchanged. Cholesterol intake decreased as well (p = 0.003). The changes in plasma total cholesterol, very low and low-density lipoprotein (VLDL+LDL) cholesterol, HDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, plasma LCAT activity and PLTP activity were not significant. Plasma CETP activity (p = 0.008) and pre beta-HDL formation (p = 0.008) decreased. The ability of plasma to promote cholesterol efflux out of fibroblasts and Fu5AH cells remained unchanged. Reduction in dietary saturated fat and cholesterol intake does not adversely affect cellular cholesterol efflux to plasma from type 1 diabetic patients, despite a drop in pre beta-HDL formation.

The influence of the ACE ( I/D) polymorphism on systemic and renal vascular responses to angiotensins in normotensive, normoalbuminuric Type 1 diabetes mellitus.

AIM/HYPOTHESIS: The renin-angiotensin-aldosterone system is important in diabetic nephropathy, with the angiotensin-converting-enzyme DD-genotype being a renal risk factor. The D-allele is associated with higher ACE concentrations, but functional consequences in diabetes mellitus are not known. To analyse these consequences, we assessed renal and systemic responsiveness to angiotensin I infusion, with the response to angiotensin II as reference. METHODS: Uncomplicated Type 1 (insulin-dependent) diabetic patients with contrasting genotypes (11 II and 11 DD) were studied, during low (50 mmol/24 h) and liberal (200 mmol/24 h) sodium diet, during a euglycaemic clamp. Angiotensin I was infused at 4 and 8 ng.kg(-1).min(-1), 1 h each, followed by infusions of angiotensin II after a 2-h wash-out period. RESULTS: During low sodium, DD-homozygotes showed higher blood pressure sensitivity to angiotensin I ( DD 21+/-5% vs II 15+/-5%, p<0.01). With liberal sodium, no differences in blood pressure were detected, whereas angiotensin I induced a higher response of ERPF ( DD 40+/-5% vs II 35+/-4%, p<0.05) and RVR ( DD 105+/-20% and II 89+/-16% p<0.05) in DD-homozygotes. Differences were not explained by altered angiotensin II sensitivity. Multiple-linear regression analysis showed that angiotensin I induced responses of blood pressure and renal haemodynamics are higher in subjects carrying the DD-genotype. The magnitude of the responses was modulated by sodium intake and long-term glycaemic control. CONCLUSION/INTERPRETATION: This study showed that responses of blood pressure and renal haemodynamics to angiotensin I are increased in diabetic subjects carrying the DD-genotype. Genotype-associated differences in ACE concentrations could, under certain circumstances, have functional consequences in uncomplicated Type 1 diabetes mellitus.

Short-term moderate sodium restriction induces relative hyperfiltration in normotensive normoalbuminuric Type I diabetes mellitus.

AIMS/HYPOTHESIS: Type I (insulin-dependent) diabetes mellitus is associated with an increased extracellular volume. Sodium restriction might seem a logical form of treatment but data on its renal effects is conflicting. We therefore studied the effects of sodium restriction on renal haemodynamics in uncomplicated Type I diabetes mellitus. METHODS: Uncomplicated Type I diabetic patients ( n = 24) and matched control subjects ( n = 24) were studied twice in random order: after a week of 50 mmol or after 200 mmol sodium intake, respectively. The diabetic patients were studied under normoglycaemic clamp conditions. Glomerular filtration rate and effective renal plasma flow were measured as the clearances of iothalamate and hippuran, respectively. RESULTS: During liberal sodium intake, glomerular filtration, effective renal plasma flow and filtration fraction were similar between the diabetic patients and the control subjects. Sodium restriction decreased the effective renal plasma flow in both groups, whereas glomerular filtration rate only decreased in the control subjects. Consequently, in the diabetic patients, the filtration fraction was increased on low sodium (4.1 +/- 8.4 %, p < 0.05 vs liberal sodium). As a consequence, filtration fraction (24.0 +/- 2.6 vs 22.1 +/- 2.0 %, p < 0.05) and glomerular filtration (119 +/- 14 vs 110 +/- 13 ml/min, p < 0.05) were higher in the diabetic patients than in the control subjects during sodium restriction. CONCLUSION/INTERPRETATION: Short-term moderate sodium restriction induces relative hyperfiltration in uncomplicated Type I diabetes. This could indicate an increased intraglomerular pressure. Sodium restriction could be an unfavourable preventive approach in diabetes mellitus but its long-term effects are not known.

Apolipoprotein E genotype is a determinant of low-density lipoprotein cholesterol and of its response to a low-cholesterol diet in Type 1 diabetic patients with elevated urinary albumin excretion.

The effect of the apolipoprotein (apo) E genotype on the lipoprotein response to a 1 year low cholesterol diet (200 mg cholesterol per day) was evaluated in 36 patients with Type 1 diabetes mellitus with albuminuria between 10 and 200 microg min(-1). Apo E genotype was characterized by polymerase chain reaction and restriction isotyping. In 11 IDDM patients with at least one epsilon4 allele (apo E4 group), baseline serum total and low density lipoprotein (LDL) cholesterol were higher (p < 0.05 for both) than in 25 patients without an epsilon4 allele and with at least one epsilon3 allele (apo E3 group). Dietary counselling resulted in a similar decrease in cholesterol intake in both groups, whereas linoleic acid did not change. In the apo E4 group, serum total and LDL cholesterol at follow-up fell (p < 0.01 for both) to levels that were not different from those in the apo E3 group, and the changes in these parameters were greater (p < 0.02) than those in the apo E3 group. We conclude that the apo E4 allele is associated with atherogenic lipoprotein abnormalities in Type 1 DM patients with minor elevations in albuminuria when they use their habitual diet. Apo E4 carrying patients respond better to a low cholesterol diet.

High-density lipoprotein cholesterol is related to the TaqIB cholesteryl ester transfer protein gene polymorphism and smoking, but not to moderate alcohol consumption in insulin-dependent diabetic men.

In non-diabetic subjects, the high-density lipoprotein (HDL) cholesterol level is increased by alcohol and decreased by smoking. The biallelic B1B2 polymorphism of the cholesteryl ester transfer protein (CETP) gene is a genetic determinant of HDL cholesterol. We evaluated the effect of moderate alcohol consumption, the CETP gene polymorphism and clinical variables on HDL cholesterol and other lipoprotein parameters in insulin-dependent diabetic (IDDM) men. Thirteen moderate alcohol using IDDM men (median alcohol consumption 17 g/d) and 13 abstainers, individually matched for the CETP gene polymorphism and clinical factors including smoking, were studied. HDL cholesterol, serum apo AI and serum CETP activity levels were very similar in alcohol users compared to abstainers (1.36 +/- 0.28 vs 1.36 +/- 0.36 mmol l-1, 1.71 +/- 0.31 vs 1.75 +/- 0.33 g l-1 and 134 +/- 27 vs 138 +/- 53 nmol l-1h-1, respectively, n.s. for all). No significant differences in apo B-containing lipoproteins were observed. Multiple regression analysis (multiple r = 0.68) showed that HDL cholesterol was positively associated with the presence of the B2 allele (0.23 mmol l-1 higher for each B2 allele present, p = 0.004) and negatively with smoking (0.15 mmol l-1 lower per 10 cigarettes smoked daily, p = 0.011), but not with alcohol consumption (p = 0.66). This study suggests that moderate alcohol consumption has no beneficial effect on the lipoprotein profile in IDDM men. HDL cholesterol is adversely influenced by smoking, whereas considerable variation in its level appears to be explained by the CETP gene polymorphism.

Long-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension.

OBJECTIVE: To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS: We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g.kg-1.day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [125I]iothalamate and [131I]hippuran, respectively. RESULTS: In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g.kg-1.day-1 (P < 0.005), but only seven participants consumed < 0.8 g.kg-1.day-1. Protein intake was unaltered in the UPD group (P < 0.001 vs. LPD). Baseline albuminuria and renal hemodynamics were not different in the groups. In the LPD group albuminuria decreased from 36 (95% CI, 16-83) to 30 micrograms/min (95% CI, 14-67) (P < 0.05). After adjustment for MAP and diabetes duration, the decrease in albuminuria in the LPD group was 26% (95% CI, 13-36) (P < 0.001), which was significantly different from the 5% (95% CI, -10-22) change in the UPD group (P < 0.005 vs. LPD). Multiple regression analysis showed the actual decrease in protein intake lessened (P < 0.005), whereas prevailing MAP accelerated albuminuria (P < 0.001). Low-protein intake independently reduced ERPF (P = 0.009) and GFR (indirectly via ERPF, P < 0.001) after 1 yr. Only minor changes in renal hemodynamics occurred in the second yr. CONCLUSIONS: This study suggests that long-term dietary protein restriction beneficially reduces albuminuria and renal hemodynamics in IDDM patients with mildly elevated albuminuria. Systemic BP counteracts these effects even in the absence of hypertension. Suboptimal compliance limits diet efficacy.

Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion.

We conducted a 2-year prospective randomised study to investigate the effects of a linoleic-acid-enriched diet on albuminuria and lipid levels in Type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10 and 200 micrograms/min). Thirty-eight patients were randomly assigned to increase dietary polyunsaturated:saturated fatty acids ratio to 1.0 by replacement of saturated fat with linoleic-acid-rich products (n = 18, two dropouts, analysis was performed in n = 16) or to continue their usual diet (n = 20). The total fat and protein content of the diet was unaltered. Clinical characteristics, albuminuria, blood pressure, glomerular filtration rate, metabolic control and dietary composition were similar in the two groups at baseline. In the high linoleic acid diet group, linoleic intake rose from 7 +/- 4 to 11 +/- 2 energy % and polyunsaturated:saturated fatty acids ratio rose from 0.60 +/- 0.28 to 0.96 +/- 0.16 (p less than 0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p less than 0.02) and 55% (95% confidence interval, 11 to 127) (p less than 0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p less than 0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increased by 16% (95% confidence interval, -17 to 38) and glomerular filtration rate declined during the second year. Blood pressure tended to rise similarly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)