Intravenous GLP-1 [7-36 amide] can normalize fasting hyperglycaemia in Type 2 diabetic patients. Whether GLP-1 [7-37] has similar effects and how quickly plasma glucose concentrations revert to hyperglycaemia after stopping GLP-1 is not known. Therefore, 8 patients with Type 2 diabetes (5 female, 3 male; 65+/-6 years; BMI 34.3+/-7.9 kg m(-2); HbA1c 9.6+/-1.2%; treatment with diet alone (n=2), sulphonylurea (n=5), metformin (n=1)) were examined twice in randomized order. GLP-1 [7-36 amide] or [7-37] (1 pmol kg(-1)min(-1) were infused intravenously over 4 h in fasted subjects. Plasma glucose (glucose-oxidase), insulin and C-peptide (ELISA) was measured during infusion and for 4 h thereafter. Indirect calorimetry was performed. Fasting hyperglycaemia was 11.7+/-0.9 [7-36 amide] and 11.3+/-0.9 mmol l(-1) [7-37]. GLP-1 infusions stimulated insulin secretion approximately 3-fold (insulin peak 168+/-32 and 156+/-47 pmol l(-1), p<0.0001 vs basal; C-peptide peak 2.32+/-0.28 and 2.34+/-0.43 nmol l(-1), p<0.0001, respectively, with GLP-1 [7-36 amide] and [7-37]). Four hours of GLP-1 infusion reduced plasma glucose (4.8+/-0.4 and 4.6+/-0.3 mmol l(-1), p<0.0001 vs basal values), and it remained in the non-diabetic fasting range after a further 4 h (5.1+/-0.4 and 5.3+/-0.4 mmol l(-1), for GLP [7-36 amide] and [7-37], respectively). There were no significant differences between GLP-1 [7-36 amide] and [7-37] (glucose, p=0.99; insulin, p=0.99; C-peptide, p=0.99). Neither glucose oxidation nor lipid oxidation (or any other parameters determined by indirect calorimetry) changed during or after the administration of exogenous GLP-1. In conclusion, GLP-1 [7-36 amide] and [7-37] normalize fasting hyperglycaemia in Type 2 diabetic patients. Diabetes therapy (diet, sulphonyl ureas or metformin) does not appear to influence this effect. In fasting and resting patients, the effect persists during administration of GLP-1 and for at least 4 h thereafter, without rebound. Significant changes in circulating substrate concentrations (e.g. glucose) are not accompanied by changes in intracellular substrate metabolism.

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An investigation was made of 17 patients with multiple myeloma using the method of alkaline filter elution for the detection of DNA damage and the determination of sister chromatid exchange (SCE) frequency in peripheral lymphocytes during a course of chemotherapy with melphalan and prednisone. We were able to detect elevated SCE frequencies in pretreated patients that approximately doubled during the therapeutic cycle. An appreciable level of DNA cross-linking was detected by alkaline filter elution; DNA cross-linking scarcely increased during a course of chemotherapy. The increase in the SCE frequency during the first therapy cycle was even greater in the case of patients with newly diagnosed multiple myelomas. The results obtained by alkaline filter elution and measuring SCE frequencies suggest that these techniques are suitable as methods in molecular epidemiology, especially if applied to persons who are chronically exposed to cytostatic drugs. Whether or not the methods could be valuable in evaluating therapy response needs further investigation.

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