Aim To assess the vitamin B12 status of patients with type 2diabetes who had been receiving metformin treatment for at least one year. Methods Patients with type 2 diabetes attending a diabetes clinic were included in a cross-sectional cohort study. Patients exposed to metformin for more than one year (n=53) were compared with a non-exposed control group (n=31). Serum cobalamin and other variables reflecting vitamin B12 status were measured. Results Patients on metformin had lower cobalamin (289±137 vs. 395±162 pmol/L; p<0.01) and holotranscobalamin (76±49 vs. 97±41 pmol/L; p<0.05), and higher HCy (11.3+3.3 vs. 10.3±2.3 µmol/L; p<0.05); these changes were correlated. Eight metformin patients, but no controls, had holotranscobalamin below the normal range (p<0.05). Methylmalonic acid and folate were similar in both groups. Conclusion Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency. Our results highlight the necessity of checking B12 status during metformin therapy.

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The effects on blood pressure, the renin-angiotensin-aldosterone and the kallikrein-kinin systems were investigated in 32 patients with primary hypertension WHO stage I-II treated with captopril. Hydrochlorothiazide was added if needed to achieve a supine diastolic blood pressure of less than or equal to 90 mmHg. A placebo control group (n=8) was treated similarly. Supine mean arterial pressure fell from 133 +/- 10 on placebo to 114 +/- 12 mmHg after 4 weeks on captopril. At the same time plasma aldosterone decreased from 263 +/- 188 to 164 +/- 101 pmol . 1(-1), 24 h urinary excretion of aldosterone from 18 +/- 12 to 12 +/- 10 nmol and kallikrein from 9.0 +/- 6.7 to 6.2 +/- 4.1 nkat. Plasma angiotensin II was significantly reduced after two weeks treatment from 23.2 +/- 8.6 to 17.0 +/- 6.7 pmol . 1(-1). Before, but not during captopril, 24 h urinary kallikrein excretion correlated with plasma aldosterone levels and 24 h urinary aldosterone excretion (r=0.44 p, less than 0.05 and r=0.53, p less than 0.01, respectively). Mean arterial pressure reduction on captopril correlated with pretreatment PRA (r=0.44, p less than 0.05) but not with other measured hormone levels or changes therein. The addition of hydrochlorothiazide caused a further fall in blood pressure, but increased plasma aldosterone and 24 h urinary kallikrein excretion. Hydrochlorothiazide alone increased only 24 h urinary aldosterone excretion significantly. These findings indicate that, besides aldosterone secretion and renal arterial pressure, further mechanisms regulating the release of and activity of the renal kallikrein-kinin system exist.

Blood glucose profiles, fasting blood glucose and glycated haemoglobin were followed prospectively for 6 weeks in 14 patients with non-insulin-dependent diabetes (NIDDM). Capillary blood glucose was sampled weekly on filter paper and analysed in the laboratory. Glycated haemoglobin was determined every other week with both cation-exchange chromatography (HbA1-IEC) and aminophenylboronic acid affinity chromatography (GHb-PBA). The mean for the blood glucose profiles was 11.2 +/- 3.5 mmol l-1 (+/- SD) and the mean for fasting blood glucose was 9.5 +/- 2.8 mmol l-1. For individual patients the differences between mean fasting blood glucose and mean blood glucose varied from -1.3 to 4.2 mmol l-1. There was a linear relationship between blood glucose and glycated haemoglobin which was steeper for GHb-PBA than for HbA1-IEC. The correlations with fasting blood glucose and mean blood glucose for HbA1-IEC were r = 0.85 and r = 0.92 and for GHb-PBA r = 0.87 and r = 0.96 respectively. Mean blood glucose was better correlated to glycated haemoglobin than fasting blood glucose (p < 0.05 for GHb-PBA).

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The effects of once daily dosage of the two cardioselective β‐adrenoceptor blocking agents, atenolol and metoprolol, were studied in 26 patients with primary hypertension. The study was a randomized double‐blind cross‐over trial with placebo run‐in and wash‐out. Assessment of effect was performed about 1 and 25 hours after dosing. At rest, both atenolol and metoprolol lowered the blood pressure (BP) and heart rate (HR) compared to placebo. Atenolol induced a more effective BP reduction than metoprolol, especially 25 hours after drug intake. During exercise 1 hour after dosing both drugs reduced BP and HR to a similar extent, whereas 25 hours after dosing atenolol gave a more efficient BP and HR reduction than metoprolol. Our data show that both 100 mg atenolol and 100 mg metoprolol are effective antihypertensive β‐blockers at rest and during exercise, 1 hour after intake. Metoprolol was less effective than atenolol 25 hours after dosing probably due to its shorter plasma half‐life, thus implying a twice daily regimen for metoprolol in standard preparation.

1 Forty‐one patients with primary (essential) hypertension were treated with captopril alone or in combination with hydrochlorothiazide for 12‐ 36 months. 2 During an initial dose‐titration period mean blood pressure fell from 174/111 mm Hg to 134/88 mm Hg supine and from 170/116 mm Hg to 126/93 mm Hg standing after 3 months' treatment. 3 During long‐term treatment with unchanged or reduced doses of captopril or hydrochlorothiazide, or both, blood pressure remained substantially reduced. Mean supine blood pressure at 24 months was 136/90 mm Hg and at 36 months 138/90 mm Hg. 4 In 12 patients with clearly defined low renin (essential) hypertension initial blood pressure reduction was less than in patients with normal renin hypertension after 1 month's treatment (162/102 mm Hg v 143/92 mm Hg). After 24 months of treatment, however, the treatment results were similar in the two groups. 5 Except for one case of reversible proteinuria no serious side effects were seen during treatment periods of up to three years. 6 Captopril alone or in combination with hydrochlorothiazide seems to be an effective and safe drug in the long‐term treatment of primary hypertension.

Summary. Eight insulin-treated diabetic patients in good glycaemic control were studied as out-patients with frequent determinations of stable glycosylated haemoglobin (HbAlc) before, during and after 1 week of induced poor glycaemic control. Stable HbAlo was determined by cation exchange chromatography after elimination of the labile fraction by incubation in saline (0.15 tool/l). The increase in mean blood glucose was significant on the first day of reduced insulin therapy and greatest after 1 Week (6.9___ 3.9 mmol/1 above basal values). Stable HbAac increased significantly on day 7 of the reduced insulin treatment. The increase represented, on average, 0.009% of total haemoglobin per mmol/1 increase in mean blood glucose per 24 h during the period of induced hyperglycaemia. After restoring insulin therapy, a significant decrease in blood glucose was achieved on day 1 and after 2 days, the blood glucose level was similar to before the study. There was no significant decrease in stable HbAlc within the first 2 weeks of improved glycaemia.