We performed a randomized, controlled study on the dose-response effects of daily supplementation of 1.5, 3, and 6 g of the marine fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) as their ethyl esters for 12 wk in 45 healthy normotriglyceridemic male volunteers. Significant dose-related increases of the n-3 fatty acids 20:5, 22:5, and 22:6 in plasma phospholipids (p less than 0.0001) were found, corresponding roughly to decreases of the n-6 fatty acids 18:2 and 20:4 (p less than 0.001). Serum triglycerides and HDL3-cholesterol concentrations showed a dose-dependent reduction (p less than 0.05) and HDL2 cholesterol increased (p less than 0.05). Results for 3 and 6 g n-3 fatty acids were similar. No dose-dependent effects were observed in the VLDL-, LDL-, and total HDL-cholesterol subfractions; blood pressure; bleeding time; erythrocyte deformability; or capacity of polymorphonuclear leukocytes to kill Staphylococcus aureus. This study indicates that 3 g n-3 ethyl ester fatty acids appears to be the appropriate supplementation dose in humans, at least regarding lipid-profile changes and the ability to incorporate such fatty acids in the plasma phospholipids.

SummaryBackground and objectives Recent studies found different associations of cognitive function with albuminuria or estimated GFR (eGFR). Most studies were limited to the elderly or did not take both renal variables into account. Therefore, this study analyzed the association of cognitive function with albuminuria and eGFR in community-dwelling persons aged 35 to 82 years. ResultsThe prevalence of albuminuria Ͻ10, 10 to 29, and Ն30 mg/24 h was 54%, 31%, and 15%, respectively. Mean eGFR (Ϯ SD) was 79 Ϯ 15 ml/min per 1.73 m 2 . Because of interaction between albuminuria and age, analyses were performed per age tertile. After multivariate adjustment, albuminuria Ն 30 mg/24 h, but not eGFR, was associated with lower RFFT score in the youngest tertile (B Ϫ5.3; 95% CI, Ϫ0.6 to Ϫ9.2; P ϭ 0.05), but not in older tertiles. Moreover, subjects in the youngest tertile with increasing albuminuria (5-15 and Ͼ15 mg/24 h) before RFFT measurement had lower mean RFFT scores than subjects with stable albuminuria: mean difference Ϫ4.9 (P ϭ 0.3) and Ϫ6.7 (P ϭ 0.03), respectively. ConclusionsIn this community-based cohort, elevated albuminuria was associated with worse cognitive function in young but not in old persons. There was no association of eGFR with cognitive function.

1. Renal and cardiovascular effects of three dosages of insulin [50 (Ins I), 300 (Ins II) and 500 (Ins III) m-units h-1 kg-1] were investigated in healthy males by using a euglycaemic clamp technique. On separate days, control experiments were carried out to correct for any circadian variation in the variables studied. 2. All three insulin dosages resulted in a marked decline in fractional sodium excretion (actual experiments: basal, 0.95 +/- 0.15%, Ins I, 0.79 +/- 0.10%, Ins II, 0.80 +/- 0.12%, Ins III, 0.84 +/- 0.08%; control experiments: basal, 0.96 +/- 0.10%, Ins I, 1.20 +/- 0.12%, Ins II, 1.53 +/- 0.15%, Ins III, 1.43 +/- 0.10%; means +/- SEM, P less than 0.005, analysis of variance). With the highest insulin dosage, the reduction in fractional sodium excretion tended to be less striking. This coincided with a rise in heart rate, pulse pressure and pulse rate-systolic blood pressure product (double product). Although blood pressure itself did not change, systolic blood pressure also tended to increase (actual experiments: basal, 133 +/- 5 mmHg, Ins I, 132 +/- 5 mmHg, Ins II, 139 +/- 5 mmHg, Ins III, 143 +/- 4 mmHg; control experiments: basal, 128 +/- 3 mmHg, Ins I, 129 +/- 3 mmHg, Ins II, 130 +/- 3 mmHg, Ins III, 133 +/- 3 mmHg; means +/- SEM, P = 0.09, analysis of variance). There was a positive correlation between the change in fractional sodium excretion and the change in systolic blood pressure over control values (r = 0.696, P less than 0.028).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of mixing short- and intermediate-acting insulins (lente and NPH) on plasma insulin levels and action profiles, assessed by the euglycaemic clamp technique, were studied in 10 volunteers. Four protocols were used: (1) comparison between two semi-synthetic human soluble insulins in seven subjects (0.22 IU/kg); (2) assessment of insulin levels and action profiles of lente insulin in six subjects and of NPH insulin in five subjects (0.33 IU/kg); (3) comparison between mixtures of soluble with lente insulin and soluble with NPH insulin, administered immediately after mixing, in eight subjects (0.55 IU/kg, 40% short-acting); (4) same mixtures, administered 2 days after preparation, in seven subjects. No differences in insulin levels and action profiles during the first 4 h after injection were found between both short-acting insulins and the soluble + NPH insulin mixtures. After the administration of NPH insulin, plasma insulin levels rose slightly faster in comparison with lente insulin, with no significant differences between the action profiles for either insulin. Onset of action was delayed after soluble + lente insulin, both when administered immediately after mixing and to a greater extent when stored for 2 days before administration. After the latter procedure, the onset of action was markedly retarded and only slightly faster than after lente insulin alone. We conclude, therefore, that mixing soluble with NPH insulin in a ratio of 2:3 does not affect the absorption kinetics of soluble insulin, whereas the onset of action is delayed when soluble is combined in the syringe with lente insulin, even when administered immediately after mixing.

Hyperinsulinemia has been implicated in the pathogenesis of the blood pressure elevation in patients with noninsulin-dependent diabetes mellitus, obesity, but also essential hypertension.

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Repaglinide is as well tolerated as glibenclamide and is equally effective in the management of type 2 diabetes. Repaglinide may, however, offer an improvement in postprandial blood glucose control compared with glibenclamide, thereby helping to reduce the relative long-term risk of diabetic complications.

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