LONG-TERM EFFECTS OF PROTEIN-RESTRICTED DIET ON ALBUMINURIA AND RENAL-FUNCTION IN IDDM PATIENTS WITHOUT CLINICAL NEPHROPATHY AND HYPERTENSION

OBJECTIVES - 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 [I-125]iothalamate and [I-131]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 mug/min (95% Cl, 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% Cl, - 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

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 mu g min(-1). Apo E genotype was characterized by polymerase chain reaction and restriction isotyping. In 11 IDDM patients with at least one epsilon 4 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 epsilon 4 allele and with at least one epsilon 3 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. (C) 1998 John Wiley & Sons, Ltd

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-mu-g/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 <0.001 compared to usual diet group). The median increase albuminuria was 58% (95% confidence interval, 13 to 109) during the first year (p <0.02) and 55% (95% confidence interval, 11 to 127) (p <0.01) during the second year. Glomerular filtration rate remained unaltered and filtration fraction tended to rise (p <0.05 compared to usual diet group). In the usual diet group, albuminuria did not significantly increase 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. Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate. Low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group (p <0.05). High density lipoprotein cholesterol declined in both groups (p <0.05). It is concluded that a linoleic-acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in Type 1 diabetic patients with elevated urinary albumin excretion

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