INSULIN RESISTANCE IS ASSOCIATED WITH HIGH SODIUM-LITHIUM COUNTERTRANSPORT IN ESSENTIAL-HYPERTENSION

The nature of the association between essential hypertension and insulin resistance remains unknown. We measured plasma glucose and insulin levels after an oral glucose tolerance test (OGTT), as well as insulin sensitivity (using a euglycemic hyperinsulinemic clamp), glucose turnover (R(d); using [6,6-H-2(2)]- and [3-H-3]glucose isotopic dilution), and forearm net balance of glucose (using arterial-venous difference) in 22 hypertensive patients with high (H-2) red blood cell (RBC) sodium-lithium countertransport (Na+-Li+ CT; > 0.41 mmol.l RBC-1.h-1), 21 hypertensive patients with normal (H-1) Na+-Li+ CT, and 22 normotensive controls (C). After OGTT, H-2 patients had higher plasma glucose and insulin levels than H-1 and C. During euglycemic hyperinsulinemia (approximately 100-mu-U/ml) R(d) was lower in H-2 [21.7 +/- 1.4 (SE) mu-mol.kg-1.min-1] than in H-1 (44.3 +/- 2.9; P < 0.01) and C (48.1 +/- 3.0; P < 0.01), and an inverse correlation was found between rates of Na+-Li+ CT and R(d) in H-1 and H-2 (r(s) = -0.76; P < 0.01). Forearm glucose uptake was 40-50% lower in H-2 compared with H-1 and C (P < 0.01). Lactate concentration increased more in C (from 511 +/- 24 to 1,207 +/- 69-mu-M) and in H-1 (from 564 +/- 40 to 1,122 +/- 99) than in H-2 (from 581 +/- 42 to 950 +/- 102, P < 0.05 vs. both). Forearm blood flow increased more in C (31%, P < 0.05) and H-1 (22%, P < 0.05) than in H-2 (12%). A positive correlation was found between forearm glucose uptake and blood flow in H-1 and H-2 (r(s) = 0.71, P < 0.01). Plasma triglyceride concentration was higher in H-2 (2.02 +/- 0.11 mM) than in H-1 (1.32 +/- 0.08, P < 0.05) and C (1.28 +/- 0.08, P < 0.05). These data demonstrate that high Na+-Li+ CT is associated with peripheral insulin resistance in patients with essential hypertension.