Twice- rather than once-daily basal insulin is associated with better glycaemic control in Type 1 diabetes mellitus 12 months after skills-based structured education in insulin self-management.

AIM: This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus. METHOD: Retrospective analysis of data from 892 DAFNE participants from 11 UK centres. RESULTS: Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110). CONCLUSION: After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.

Variation in comedonal antibiotic concentrations following application of topical tetracycline for acne vulgaris.

A miniaturized sensitive bioassay was used to detect tetracycline in open comedones following topical twice daily application of 0.22% tetracycline hydrochloride for a minimum of 4 weeks to the facial skin of patients with mild to moderate acne. The lower limit of detection was 4.8 +/- 0.8 ng per comedone or per 10 microliters. Using this method, 111 of 155 open comedones from 15 patients were found to contain a detectable amount of tetracycline, ranging from 1.8 to 156.9 ng per comedone, and between 4.5 and 1140.1 ng per mg comedonal material. There was a significant effect of comedone weight on tetracycline content, with smaller comedones containing proportionately more tetracycline. The Spearman rank correlation coefficient was -0.5619 (P < 0.001). All 111 comedones in which tetracycline was detected contained sufficient drug to inhibit fully antibiotic-sensitive propionibacteria. However, conditions favourable to the selection and overgrowth of highly tetracycline-resistant strains (MIC > or = 32 micrograms/ml) prevailed in at least 18.7% (29 of 155) of the comedones tested.

Tetracycline-resistant propionibacteria from acne patients are cross-resistant to doxycycline, but sensitive to minocycline.

Antibiotic-resistant propionibacteria are being isolated with increasing frequency from antibiotic-treated acne patients. Minimum inhibitory concentrations (MICs) of three tetracyclines, extensively used in acne therapy, were determined for 46 resistant and 19 sensitive propionibacteria isolates. Sensitive strains were inhibited by < or = 1 microgram/ml of all three tetracyclines. For every resistant strain tested, the MIC of tetracycline exceeded that of doxycycline which, in turn, exceeded that of minocycline. The mean MIC for resistant strains was 20.61 +/- 4.56 micrograms/ml of tetracycline, 9.70 +/- 2.03 micrograms/ml of doxycycline and 1.95 +/- 0.35 micrograms/ml of minocycline. In order to determine whether these strains could be inhibited by concentrations of minocycline achievable in vivo, serum levels of minocycline were determined in acne patients receiving either the recommended dose of 50 mg b.d. (20 males, 14 females), or twice this dose (21 males, 12 females). Serum levels were significantly higher (P < 0.001, Student's t-test) in patients receiving 100 mg b.d. Males on 50 mg b.d. had significantly lower serum levels than females on the same dose (P < 0.05. Student's t-test). For all patients, the mean serum level on high-dose minocycline was 2.46 +/- 0.45 micrograms/ml, compared with 1.38 +/- 0.30 micrograms/ml on the smaller dose. These results indicate that tetracycline-resistant propionibacteria should be considered clinically minocycline sensitive, if patients who harbour such strains are prescribed 100 mg b.d. The recommended dose of minocycline for treating acne, especially in male patients, should be re-assessed.

Comparison of serum antibiotic levels in acne patients receiving the standard or a modified release formulation of minocycline hydrochloride.

Serum levels of minocycline hydrochloride were determined by bioassay in a total of 223 acne patients (123 male, 100 female) receiving either the recommended dose (100mg/day) or a high dose (200mg/day) of the standard preparation (101 patients) of a modified release formulation (132 patients). Sera were collected within 6 h of the morning dose 7-10 days after the start of treatment. Mean minocycline serum levels were consistently higher in females than in males, irrespective of dose or formulation. The differences only reached statistical significance (P < 0.05, Student's t-test) in the case of the standard preparation at a dose of 50 mg, b.d. Serum levels were increased significantly in both sexes at the higher dosage of each formulation (P < 0.01) but there was no significant difference between formulations at either dosage. Variation in serum concentrations was not accounted for by variation in body mass. Serum levels above the modal minimum inhibitory concentration (MIC) of minocycline for fully sensitive strains of Propionibacterium acnes I (0.125 micrograms/mL) were recorded in all patients. In contrast, serum levels equal to or greater than the modal MIC of minocycline for resistant propionibacteria (2 micrograms/mL) were recorded in only 17.9% of patients on the low dose standard preparation compared with 55.6% on the high dose standard preparation (P < 0.001, chi 2). Even in females on the high-dose modified release formulation, 32.2% had serum levels below the modal MIC of minocycline for resistant strains. We conclude that, in terms of achievable serum levels over a short time period, there is no advantage of the modified release formulation over the standard preparation of minocycline. Whichever formulation is used, dose manipulation may be necessary to achieve maximum therapeutic benefit, especially in those individuals who are colonized by propionibacteria with reduced sensitivity to minocycline.