Sodium-Lithium Countertransport Activity and Insulin Resistance in Normotensive IDDM Patients

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na⁺/Li⁺ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (≈ 719 pM [≈ 100 μU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na⁺/Li⁺ CT activity (mean 0.47, range 0.42–0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na⁺/Li⁺ CT activity (mean 0.24, range 0.12–0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean ± SE 36 ± 2 vs. 33 ± 1 yr), duration of diabetes (19 ± 3 vs. 18 ± 2 yr), body mass index (26 ± 0.8 vs. 24 ± 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 ± 4/79 ± 2 vs. 122 ± 3/77 ± 2 mmHg), and glycemic control (HbA₁ 8.5 ± 0.4 vs. 8.0 ± 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) μg/min in group 1 and between 2.7 and 93 (geometric mean 11) μg/min in group 2. There were four microalbuminuric patients (AER > 30 μg/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 ± 2.2 μmol.kg⁻¹ · min⁻¹ [7.48 ± 0.4 mg.kg⁻¹ · min⁻¹] vs. 49.6 ± 2.2 μmol.kg⁻¹ · min⁻¹ [8.93 ± 0.4 mg·kg⁻¹ · min⁻¹ P = 0.03), but some overlap existed between the two groups. dilution with [3-³H]glucose, was similarly suppressed in both study groups. The proportion of echocardiographically determined left ventricular hypertrophy was significantly higher in patients with high Na⁺/Li⁺ CT (33 vs. 0%, P = 0.046). Triglycerides (TG), the ratio of low-density lipoprotein (LDL) to high-density lipoprotein (HDL), and apolipoprotein B (apoB) were higher in group 1 (median [range] TG 0.90 [0.51–1.64] vs. 0.52 [0.37–1.26] mM, P = 0.002, LDL-HDL ratio 3.36 [1.43–5.72] vs. 2.28 [1.21–3.33], P = 0.019, apoB 1.06 [0.54–1.16] vs. 0.80 [0.61–1.33] g/L, P = 0.03). In clinically nonproteinuric normotensive IDDM patients, increased Na⁺/Li⁺ CT activity is associated with reduced insulin sensitivity, left ventricular hypertrophy, and lipid disturbances. These abnormalities either singly or in combination may contribute to vascular damage in a subset of patients with IDDM.