ENDOGENOUS DIGOXIN-LIKE IMMUNOACTIVITY IN SUBJECTS WITH DIABETES-MELLITUS AND HYPERTENSION

The serum concentrations of digoxin-like immunoactivity (DLIA) were me asured in 99 patients: 20 healthy volunteers (HV), 15 patients with in sulin-dependent diabetes mellitus (IDDM), 14 patients with non-insulin -dependent diabetes mellitus without hypertension taking oral hypoglyc emic (OHA) agents (NIDDM/-HT), 11 patients with NIDDM without hyperten sion taking insulin (NIDDM/-HT+INS), 12 NIDDM patients with hypertensi on taking OHA (NIDDM/+HT), nine NIDDM patients with hypertension takin g insulin (NIDDM/+HT/+INS), 10 patients with essential hypertension wi th normal insulin levels (HT/-HI), and in eight patients with essentia l hypertension with hyperinsulinemia (HT/+HI). The numbers (%) of subj ects with DLIA levels above the detection limit of the assay used (> 0 .1 nmol/L) were, in the NIDDM/-HT group, 12/14 (85.7%) and in the NIDD M/+HT group, 9/12 (75%), significantly higher (P <.05) than in the HV (7/20; 35%), IDDM (3/15; 20%), and HT/-HI groups (2/10; 20%). The numb er and percentage of subjects with DLIA levels above the detection lim it in the HT/+HI group was six of eight (75%), significantly (P <.05) higher than in the IDDM and HT/-HI groups, and tended to be higher tha n in the HV group (P <.055). Means and SD of serum DLIA levels (nmol/L ) in the NIDDM/-EH (0.18/0.09) and NIDDM/+EH (0.19/0.15) groups were s ignificantly higher (P <.05) than in the HV (0.09/ 0.07), IDDM (0.05/0 .05), and EH/-HI (0.06/0.06) groups. DLIA levels in the HT/+HI group ( 0.15/0.12) were significantly higher (P <.05) than in the IDDM and HT/ -HI groups. The percentage of DLIA levels above the detection limit, a s well as the mean and SD of DLIA in the NIDDM group taking OHA, did n ot differ from those in subjects taking insulin. In all subjects studi ed (n = 99), DLIA correlated with C-peptide (r = 0.30; P <.01) and glo merular filtration (GF) (r =- 0.21; P <.05). After exclusion of insuli n-treated patients, DLIA correlated significantly with plasma glucose (PG; r = 0.25; P <.05), immunoreactive insulin (IRI; r = 0.41; P <.001 ), C-peptide (r = 0.27; P <.05), and GF (r =- 0.26; P <.05) (n = 64). Correlation of DLIA with IRI (r = 0.33; P <.05; n = 38) also persisted after exclusion of patients taking insulin and those with DLIA levels below the detection limit. Similarly, DLIA also correlated with C-pep tide (r = 0.64; P <.05) and IRI (r = 0.70; P <.05) in the subgroup of 10 patients with the highest levels of DLIA (> 0.25 nmol/L). None of t he sera (n = 15) with different DLIA concentrations (0.0-0.38 nmol/L) exhibited K-pNPPase (Na+-K+-ATPase) inhibitory activity. In conclusion , this work demonstrated elevated serum DLIA in NIDDM and HT/+HI patie nts, and its correlation with IRI and GF. However, due to the fact tha t the chemical nature and biologic properties of DLIA are still a matt er of debate, it is too early to speculate whether the elevation of DL IA is just a secondary result associated with HI and reduced GF, or wh ether it also has pathophysiologic consequences. Nevertheless, in both eases the elevated concentrations of substances with DLIA and their i nterference with antidigoxin antibodies may affect therapeutic monitor ing of digitalization in NIDDM and HT/+HI patients. Also, the elevated DLIA could subclassify these patients. The significance of such subcl assifications (pathophysiologic, therapeutic, or prognostic), however, will need further investigation. (C) 1998 American Journal of Hyperten sion, Ltd.