Cimetidine reduces weight and improves metabolic control in overweight patients with type 2 diabetes.

OBJECTIVE: To investigate the weight-reducing effect of cimetidine in overweight patients with Type 2 diabetes. DESIGN: A 12-week clinical intervention study of 400 mg cimetidine prescribed three times daily in a randomised, double-blind, placebo-controlled design. SUBJECTS: Forty-three overweight patients with Type 2 diabetes (age 18-65 y, body mass index (BMI) 27.2-48.2 kg/m2). MEASUREMENTS: Body weight, BMI, body fat, waist and hip circumference, waist/hip ratio, blood pressure, fasting blood glucose, HbA1c, plasma concentrations of insulin, insulin/glucose ratio and lipids at the start and after 12 weeks, and daily recordings of appetite. RESULTS: Subjects given cimetidine (n = 19) and placebo (n = 24) lost 5.0 +/- 2.2 kg (mean +/- s.d.) and 1.3 +/- 1.1 kg, respectively. Significant reductions were observed in appetite, body fat (29.9 +/- 6.6% to 25.3 +/- 7.4%), waist circumference (111.5 +/- 10.3 cm to 107.4 +/- 10.6 cm), waist/hip ratio (0.96 +/- 0.08 to 0.94 +/- 0.08), and systolic and diastolic blood pressure (reductions of 6.9 +/- 11.4 mm Hg and 6.0 +/- 6.6 mm Hg, respectively) in cimetidine group only. Significant decreases in fasting concentrations of blood glucose, HbA1c, plasma insulin, insulin/glucose ratio, plasma triglycerides and a significant increase in plasma high-density lipoprotein cholesterol were observed in the cimetidine group only. CONCLUSIONS: Cimetidine reduces appetite and body weight, and improves metabolic control in overweight subjects with Type 2 diabetes.

Autonomous hyperparathyroidism in X-linked hypophosphataemia.

Four patients with familial hypophosphataemic rickets developed significant hypercalcaemia which persisted after discontinuation of vitamin D therapy. They had increased PTH levels and were operated for hyperparathyroidism at the ages of 18, 20, 24 and 45 years, respectively. Three of the patients had previously received phosphate treatment and one patient developed hyperparathyroidism 7 years after treatment with calcitriol. Histological evaluation revealed different degrees of parathyroid hyperplasia in all patients, with persistently increased PTH and/or calcium levels after surgery. The possibility of autonomous hyperparathyroidism should be evaluated in the follow-up of patients with X-linked hypophosphataemic rickets.

The cyclic diguanylic acid regulatory system of cellulose synthesis in Acetobacter xylinum. Chemical synthesis and biological activity of cyclic nucleotide dimer, trimer, and phosphothioate derivatives.

An unusual compound, cyclic-bis(3'----5') diguanylic acid (c-di-GMP or cGpGp), is involved in the regulation of cellulose synthesis in the bacterium Acetobacter xylinum. This cyclic dinucleotide acts as an allosteric, positive effector of cellulose synthase activity in vitro (Ka = 0.31 microM) and is inactivated via degradation by a Ca2(+)-sensitive phosphodiesterase, PDE-A (Km = 0.25 microM). A series of 13 analogs cyclic dimer and trimer nucleotides were synthesized, employing a phosphotriester approach, and tested for the ability to mimick c-di-GMP as activators of cellulose synthase and as substrates for PDE-A. Seven of the synthetic compounds stimulate cellulose synthase activity and all of these activators undergo the Ca2(+)-inhibited degradation reaction. The order of affinities for synthase activators is cGpGp approximately cdGpGp approximately cGp(S)Gp (S-diastereomer) greater than cIpGp greater than cdGpdGp greater than cXpGp greater than cIpIp greater than cGp(S)Gp (R-diastereomer). Three cyclic dinucleotides of negligible affinity for either enzyme are cApAp, cUpUp, and cCpCp. This same order of affinities essentially pertains to the analogs as inhibitors of PDE-A activity, but at least one cyclic dinucleotide, cXpXp, which does not bind to cellulose synthase, is also a substrate for the degradation reaction, demonstrating that although the two enzymes share a similar, high degree of specificity for c-di-GMP, their cyclic dinucleotide binding sites are not identical. Phosphodiester bonds of activators in which an exocyclic oxygen is replaced with an atom of sulfur (cGp(S)Gp isomers) resist the action of PDE-A, and such derivatives may be prototypes for synthetic non-hydrolyzable c-di-GMP analogs.

[Treatment of diabetes and quality of life. On possibilities of a more normalized life style using an insulin pen for multi-injection therapy]. / Diabetesbehandling og livskvalitet. Om muligheter til mer normalisert livsmønster ved bruk av mangeinjeksjonsbehandling med insulinpenn.

Forty-eight insulindependent diabetics were interviewed by a psychologist about their experiences when changing from conventional diabetes regimen to multi-injection therapy using NovoPen (a pen-like insulin injection system). They had then used the new therapy for 1 1/2 years. Most of them had made only small changes in their eating habits, but they strongly appreciated the new possibility for flexibility in eating patterns. The most mentioned advantages were: The new therapy was practical and easy to use, gave more freedom, made social life easier and improved blood glucose control. Many, mainly women, experienced less feelings of guilt, and women also placed the social advantages highest on the list of advantages. The youngest persons thought the greatest benefit was increased freedom, and persons in middle age the possibilities for improved metabolic control. Multi-injection insulin therapy is an important advancement, and is probably not acceptable to most diabetics without a practical and reliable insulin pen.

Pulmonary excretion of methanol in man.

An otherwise healthy methanol-poisoned male was treated with ethanol and forced diuresis. No acidosis or visual symptoms occurred. His blood ethanol concentrations varied between 10.7 and 30.0 mmol/l (0.49-1.38 g/l). His maximal blood methanol concentration was 14.4 mmol/l (0.45 g/l) and his plasma formate levels were within reference range (0.11-0.29 mmol/l). In a 24 h period where methanol metabolism was blocked by ethanol, the total body clearance and renal clearance of methanol were 11.3 and 5.7 ml/min, respectively. The difference, 5.6 ml/min, to a large extent reflects the pulmonary clearance of methanol thus being low in man.

Pancreatic affection after acute hypotonic hemodialysis.

Four male outpatients, all on stable long-term hemodialysis, were by accident simultaneously exposed to hypotonic dialysate. Three of them developed increased serum amylase values and one died from the consequences of a fulminant pancreatitis, which had been verified by laparatomy.