AIMS/HYPOTHESIS: To investigate the effect of oral calcium (Ca(2+)) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca(2+) ([Ca(2+)](i)) and the transmembrane sodium-hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.PATIENTS AND METHODS: In this parallel randomized controlled single-blinded trial, 31 patients were allocated to receive either 1500 mg of Ca(2+) orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8-week period insulin sensitivity, [Ca(2+)](i) and the first isoform of NHE (NHE-1) activity were measured.RESULTS: At the end of the study, subjects who received Ca(2+) supplementation showed higher insulin sensitivity (Delta M-value 0.32 +/- 0.5 mmol/min P < 0.05) and lower [Ca(2+)](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P < 0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P < 0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca(2+)](i) significantly determined insulin sensitivity change (beta = -0.36, P < 0.05).CONCLUSIONS/INTERPRETATION: Oral Ca(2+) supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca(2+). NHE-1 activity was also reduced after Ca(2+) supplementation but its role in insulin sensitivity requires further investigation.