Effect of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension.

OBJECTIVE: It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mechanisms such as a reduction in oxidative stress is not clear. We investigated the influence of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension. METHODS: Thirteen patients were included in this randomized, double-blind, crossover study; they received losartan 50 mg twice daily for 4 weeks followed by atenolol 50 mg twice daily or vice versa. Concomitant medication with renin-angiotensin blocking agents or beta-blockers was withdrawn, whereas other medication remained unchanged. At baseline and after each treatment period, flow-mediated dilation of the brachial artery and oxidative stress were measured in serum samples. RESULTS: Flow-mediated dilation was increased significantly after 4 weeks' treatment with losartan (3.4 +/- 0.44%) compared with atenolol (2.58 +/- 0.42%; P = 0.01). 8-Isoprostanes, a marker of oxidative stress, were significantly reduced in the losartan group compared with baseline (0.039 +/- 0.007 versus 0.067 +/- 0.006 ng/ml; P = 0.01), but did not differ from baseline with atenolol. Glucose, hemoglobin A1c, highly sensitive C-reactive protein, lipids and systolic blood pressure remained unaltered, whereas diastolic blood pressure tended to be lower in the atenolol group. CONCLUSIONS: This study demonstrates that losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker.

Mini-Mental State Examination is superior to plasma glucose concentrations in monitoring patients with suspected hypoglycaemic disorders during the 72-hour fast.

OBJECTIVE: To determine whether systematic evaluation of cognitive function by the Mini-Mental State Examination (MMSE) allows the objective detection and documentation of cognitive deterioration in patients referred for evaluation of suspected hypoglycaemic disorders by the 72-h fast. DESIGN: Prospective case series. METHODS: In 50 patients referred for evaluation of suspected hypoglycaemic disorders, the MMSE score (maximum 30 points) was assessed at the start and at the end of the fast. RESULTS: The fast was terminated before 72 h in 14 patients because they developed neuroglycopenic symptoms due to hypoglycaemic disorders. Their MMSE score fell from a median of 29 points (range 20-30) at the beginning to 17 points (range 0-24) at the termination of the fast. The score dropped by > or =6 points in all patients with hypoglycaemic disorders. Median (range) plasma glucose concentration at the end of the fast was 2.1 (1.1-2.5) mmol/l. Thirty-six individuals developed no neuroglycopenic symptoms throughout the 72-h fast, their MMSE score remained between 27 and 30 throughout the fast and their median plasma glucose concentration dropped to 2.9 (2-3.6) mmol/l. CONCLUSIONS: Systematic evaluation of cognitive function by the MMSE at the beginning and at the termination of the fast allows objective determination and documentation of the deterioration of the cognitive state in patients with hypoglycaemic disorders. A decline in the cognitive performance by > or =6 points in the MMSE score rather than a distinct plasma glucose concentration should be used as the criterion to terminate the prolonged fast before 72 h.

Serum cystatin C is sensitive to small changes in thyroid function.

BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function. The impact of mild thyroid dysfunction on CysC has never been investigated. METHODS: CysC was determined at the time of diagnosis of subclinical hypo- and hyperthyroidism, and when TSH returned into the normal range in 40 consecutive patients with mild thyroid dysfunction. RESULTS: Twenty-six patients with subclinical hypothyroidism and 14 patients with subclinical hyperthyroidism were included. In patients with subclinical hypothyroidism median (range) TSH was 7.8 (4.3-26.7) mU/l (reference 0.27-4.2) at diagnosis and decreased to 2.3 (0.36-4.0) mU/l following treatment with levothyroxine. Mean (+/-S.D.) CysC increased from 0.88+/-0.23 mg/l (reference 0.63-1.33) in the hypothyroid state to 1.01+/-0.21 mg/l when TSH normalized (p<0.001). In patients with subclinical hyperthyroidism, median TSH at diagnosis was 0.08 (0.001-0.26) mU/l and increased to 1.6 (0.28-4.0) mU/l in the euthyroid state. CysC declined from 1.04+/-0.29 mg/l at diagnosis of subclinical hyperthyroidism to 0.91+/-0.25 mg/l when TSH normalized (p<0.05). CONCLUSIONS: Mild thyroid dysfunction significantly alters CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function.

Impact of thyroid dysfunction on serum cystatin C.

BACKGROUND: Serum cystatin C (CysC) is a novel marker for kidney function that has been claimed to be superior to serum creatinine. Thyroid dysfunction may alter creatinine, which has been found to be increased in hypothyroidism and decreased in hyperthyroidism. This study was performed to evaluate whether changes in CysC and creatinine are parallel during the treatment of hypo- and hyperthyroidism, respectively. METHODS: Prospective case series of 22 consecutively referred patients with thyroid dysfunction. Creatinine and CysC were determined at the time of diagnosis of hypo- and hyperthyroidism, and when free thyroxine (fT4) returned into the normal range. Hypothyroid patients were treated with levothyroxine. Hyperthyroid patients were treated with antithyroid drugs, surgery, or radioiodine. RESULTS: Nine patients with hypothyroidism and 13 patients with hyperthyroidism were included. In patients with hypothyroidism mean fT4 (+/-SD) was 4.9 +/- 2.5 pmol/L (reference, 12 to 22) at diagnosis and increased to 16.6 +/- 3.6 pmol/L when patients were treated with levothyroxine. Creatinine decreased from 86 +/- 13 micromol/L (reference, 70 to 105) in the hypothyroid state to 76 +/- 16 micromol/L when fT4 normalized (P = 0.062), whereas CysC increased from 0.84 +/- 0.17 mg/L (reference, 0.63 to 1.33) to 1.1 +/- 0.28 mg/L (P < 0.001). In patients with hyperthyroidism, mean fT4 was 54.6 +/- 22.7 pmol/L (reference, 12 to 22) at diagnosis and decreased to 15.8 +/- 3.6 pmol/L following treatment with antithyroid drugs, thyroid surgery, or radioiodine. Creatinine increased from 67 +/- 15 micromol/L at diagnosis of hyperthyroidism to 75 +/- 9 micromol/L when fT4 normalized (P = 0.004), whereas CysC declined from 1.32 +/- 0.17 mg/L to 0.95 +/- 0.19 mg/L (P < 0.001). CONCLUSION: Thyroid dysfunction has a major impact on CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function. In contrast to creatinine concentrations, CysC levels are lower in the hypothyroid and higher in the hyperthyroid state as compared with the euthyroid state.