Markers of endothelial dysfunction and concentrations of proinflammatory cytokines in Type II diabetes are not influenced by improved glycaemic control over 16 weeks. Improved metabolic control with insulin could, however, be associated with reduced concentrations of the acute phase marker C-reactive protein.

We have found similar relationships between concentrations of proinsulin-like molecules and prevalent coronary heart disease, as are observed for insulin in these nondiabetic subjects, although these molecules comprise only approximately 10% of all insulin-like molecules. It appears biologically implausible that these relationships represent cause and effect.

1. The aim of this study was to determine the effects of high (220 mmol/day) and low (40 mmol/day) salt intake for 6 days on blood pressure, leg blood flow and insulin sensitivity in 18 healthy normotensive subjects. 2. Twenty-four-hour ambulatory blood pressure was measured at baseline, during salt-loading and salt-depletion. Insulin sensitivity was determined by a two-step euglycaemic-hyperinsulinaemic clamp (low and high insulin infusion rates: 40 and 600 m-unit.min-1.m-2 respectively) and leg blood flow by plethysmography. 3. Salt-loading resulted in changes in weight [change between salt-loading and salt-restriction: delta=+0.45 (S.D. +/-0.69) kg, P=0.015], plasma renin [delta=-11.5 (S.D.+/-12.9) micro-units/l, P=0.001] and urinary noradrenaline [delta=-8.6 (S.D. +/-18.7) nmol/mmol creatinine, P=0.05]. There were borderline significant increases in 24-h systolic blood pressure [delta=+5.8 (S. D.+/-14.2) mmHg, P=0.06] and plasma volume [delta=+0.29 (S.D.+/-0. 67) litres, P=0.08]. 4. Insulin sensitivity was similar in both salt states. Geometric mean metabolic clearance rate of low-dose insulin: low salt, 5.13 (S.D.x//1.35) dl/min; high salt, 4.94 (S.D.x//1.37) dl/min, P=1.0. Geometric mean metabolic clearance rate of high-dose insulin: low salt, 9.68 dl/min (S.D.x//1.30); high salt, 9.68 (S.D. x//1.27) dl/min, P=0.69. 5. Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt. Percentage change of blood flow on low salt, delta=+36.6 (S.D.+/-22. 9)% versus high salt, delta=+66.8 (S.D.+/-52.2)%, P=0.03. 6. There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate. 7. We conclude that salt-loading, despite changing body weight, the renin-angiotensin-aldosterone system, urinary noradrenaline and the leg blood flow response to insulin, has no significant effect on insulin sensitivity. Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal.

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