Diabetologia

Parving, H.; Kastrup, H.; Smidt, U.; Andersen, A.; Feldt-Rasmussen, B.; Christiansen, J.

doi: 10.1007/BF00276965pmid: 6442240

125 27 27 6 6 Dr. H. -H. Parving H. Kastrup U. M. Smidt A. R. Andersen B. Feldt-Rasmussen J. Sandahl Christiansen Hvidöre Hospital Klampenborg Department of Clinical Physiology Bispebjerg Hospital Copenhagen Medical Department F Herlev Hospital Copenhagen Steno Memorial Hospital Gentofte Denmark Summary The effect of acute lowering of arterial blood pressure upon kidney function in nephropathy was studied in 13 patients with long-term Type 1 (insulin-dependent) diabetes. Ten normal subjects (six normotensive and four hypertensive) and five short-term Type 1 diabetic patients without nephropathy served as controls. Renal function was assessed by glomerular filtration rate (single bolus 51 Cr-EDTA technique) and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the subjects receiving an intravenous injection of either clonidine (225 μg) or saline (0.154 mmol/l). The arterial blood pressure was similar in the diabetic patients with nephropathy (mean 136±11 mmHg) and in the non-diabetic control subjects 88±5 (mean 140±25 mmHg). The clonidine injection induced sim- 92±15 ilar reductions in mean arterial blood pressure in all three groups (16–18 mmHg). While glomerular filtration rate and urinary albumin excretion rate remained unchanged in both control groups after clonidine injection, glomerular filtration rate dimished from 78 to 71 ml/min per 1.73 m 2 ( p <0.01), and urinary albumin excretion declined from 1707 to 938 μg/min ( p <0.01) in the patients with diabetic nephropathy. Our results suggest that an intrinsic vascular (arteriolar) mechanism underlying the normal autoregulation of glomerular filtration rate, i. e. the relative constancy of glomerular filtration rate that occurs in response to rather wide variations in perfusion pressure, is defective in diabetic nephropathy.

Gouédard, H.; Ménez, J.; Meskar, A.; Caroff, J.; Lucas, D.; Legendre, J.

doi: 10.1007/BF00276966pmid: 6530050

125 27 27 6 6 Dr. H. A. Gouédard J. F. Ménez A. Meskar J. Caroff D. Lucas J. M. Legendre Departments of Paediatrics and Neonatology Hôpital Morvan Brest France Department of Biochemistry A Hôpital Morvan Brest France Department of Nuclear Medicine Hôpital Morvan Brest France Summary The glycaemic control of infants and of their mothers was studied at delivery and on day 7 after birth in 11 control and 20 insulin-dependent diabetic women. At delivery, venous blood glucose was lower in infants of diabetic mothers compared with control infants ( p <0.02). Seven days after birth, no significant difference in blood glucose could be found between control and infants of diabetic mothers. C-peptide levels were higher in infants of diabetic mothers compared with control infants ( p <0.01). On day 7 after birth, the C-peptide levels remained higher only in infants of Class B, C, D diabetic mothers. Glycosylated haemoglobin was lower in the venous blood of infants than of their mothers ( p <0.001). Glycosylated haemoglobin was lower in control mothers than in diabetic mothers ( p <0.05), but it was higher in the venous blood samples from control infants compared with infants of diabetic mothers at delivery ( p <0.05) and 7 days after ( p < 0.01). At delivery infants' glycaemia and infants' glycosylated haemoglobin correlated ( r =0.44, p <0.02). C-Peptide and glycosylated haemoglobin levels in infants at delivery also correlated ( r = –0.42, p <0.05).

Heine, R.; Bilo, H.; Fonk, T.; Veen, E.; Meer, J.

doi: 10.1007/BF00276967pmid: 6397384

125 27 27 6 6 Dr. R. J. Heine H. J. G. Bilo T. Fonk E. A. van der Veen J. van der Meer Department of Internal Medicine Free University Hospital Amsterdam The Netherlands Departments of Endocrinology Free University Hospital Amsterdam The Netherlands Summary The effects of mixing short- and intermediate-acting insulins (lente and NPH) on plasma insulin levels and action profiles, assessed by the euglycaemic clamp technique, were studied in 10 volunteers. Four protocols were used: (1) comparison between two semi-synthetic human soluble insulins in seven subjects (0.22 IU/kg); (2) assessment of insulin levels and action profiles of lente insulin in six subjects and of NPH insulin in five subjects (0.33 IU/kg); (3) comparison between mixtures of soluble with lente insulin and soluble with NPH insulin, administered immediately after mixing, in eight subjects (0.55IU/kg, 40% short-acting); (4) same mixtures, administered 2 days after preparation, in seven subjects. No differences in insulin levels and action profiles during the first 4 h after injection were found between both short-acting insulins and the soluble + NPH insulin mixtures. After the administration of NPH insulin, plasma insulin levels rose slightly faster in comparison with lente insulin, with no significant differences between the action profiles for either insulin. Onset of action was delayed after soluble + lente insulin, both when administered immediately after mixing and to a greater extent when stored for 2 days before administration. After the latter procedure, the onset of action was markedly retarded and only slightly faster than after lente insulin alone. We conclude, therefore, that mixing soluble with NPH insulin in a ratio of 2:3 does not affect the absorption kinetics of soluble insulin, whereas the onset of action is delayed when soluble is combined in the syringe with lente insulin, even when administered immediately after mixing.

Archer, A.; Roberts, V.; Watkins, P.

doi: 10.1007/BF00276968pmid: 6530051

125 27 27 6 6 A. G. Archer V. C. Roberts Dr. P. J. Watkins Diabetic Department King's College Hospital London UK Biomedical Engineering Department King's College Hospital London UK Summary Peripheral blood flow is known to be qualitatively increased in diabetic patients with neuropathy. We have measured the actual blood flow in the feet of diabetic patients with neuropathy using non-invasive mercury strain gauge plethysmography and Doppler sonogram techniques and shown that it is increased on average five times above normal at an ambient temperature of 20 °–22 °C. Moreover, reduction of this high flow by sympathetic arousal stimuli proved possible in those with severe painful neuropathy contrasting strongly with failure to reverse it in those with severe non-painful sensory neuropathy. Reduction of blood flow was associated with reduction in neuropathic pain. We studied 22 diabetic patients with severe sensory neuropathy and eight with painful neuropathy. High resting foot blood flows were demonstrated in both groups with neuropathy. The big toe flow in those with severe sensory neuropathy was 29.3±9.2 ml · min −1 · 100 ml −1 (mean±SD) and in the painful neuropathy group, 25.9±7.5, compared with 5.2±2.4ml · min −1 · 100ml −1 in the non-diabetic control subjects ( p <0.001). High foot skin temperatures were also recorded in the groups with neuropathy, reflecting the high blood flow. The subjects with painful neuropathy retained the ability to constrict peripheral blood vessels in response to arousal stimuli, and reduce peripheral flow on average by 32% compared with the patients with sensory neuropathy who responded on average by only 10%. The demonstration of a peripheral sympathetic defect, responsible for the high blood flow and the potential reversal of such flow in painful neuropathy may be important in our further understanding of the aetiology of such pain and its treatment.

Welborn, T.; Knuiman, M.; McCann, V.; Stanton, K.; Constable, I.

doi: 10.1007/BF00276969pmid: 6530052

125 27 27 6 6 Dr. T. A. Welborn M. Knuiman V. McCann K. Stanton I. J. Constable Departments of Medicine, Ophthalmology and Mathematics University of Western Australia Nedlands Western Australia Department of Endocrinology and Diabetes Queen Elizabeth II Medical Centre 6009 Perth Western Australia Summary A cross-sectional study of 1084 Caucasoid diabetic subjects in rural Western Australia revealed a high rate of clinical macrovascular disease (46%), including coronary heart disease (13%), stroke (8%), and peripheral vascular disease (38%). Age was the major time-related variable for total macrovascular disease and for peripheral vascular disease, with identical prevalence rates in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes when age was taken into account. In 179 Type 1 diabetic subjects, logistic regression analysis showed no associated risk factors other than age. In 905 Type 2 diabetic subjects the independent risk factors for total macrovascular disease, identified by a forward stepwise selection procedure, were age as the major contributor, with plasma creatinine levels and plasma glucose levels (all p <0.001), high-density lipoprotein cholesterol levels, serum total cholesterol levels, and the (supine-erect) systolic blood pressure difference (all p <0.05). There were no direct associations with percentage desirable weight, cigarette smoking or male sex. Type 2 diabetic subjects demonstrated a very strong negative association between high-density lipoprotein cholesterol levels and coronary heart disease, and significant associations were found also between plasma glucose levels and coronary heart disease ( p <0.01), and glycosylated haemoglobin levels and peripheral vascular disease ( p <0.001).

Jarrett, R.; Murrells, T.; Shipley, M.; Hall, T.

doi: 10.1007/BF00276970pmid: 6543350

125 27 27 6 6 Professor R. J. Jarrett T. J. Murrells M. J. Shipley T. Hall Department of Community Medicine Guy's Hospital Medical School County Hall London UK Unit for Metabolic Medicine Guy's Hospital County Hall London UK Department of Medical Statistics and Epidemiology London School of Hygiene and Tropical Medicine County Hall London UK Greater London Council County Hall London UK Summary Blood glucose screening results, obtained using two different screening procedures, are reported from two occupational groups. Post-prandial blood glucose levels were measured in 3346 subjects aged 45 years or more employed by the Greater London Council/Inner London Education Authority. In women, mean blood glucose levels were higher in the afternoon than the morning ( p <0.05). Ninety-fifth centile levels were substantially higher in the afternoon in both sexes, though the differences were not constant in all age and sex sub-groups. In both sexes mean glucose levels were highest in the winter (December–February, inclusive), but seasonal variation did not significantly affect the proportion exceeding the ninety-fifth centile for the total population. In the Whitehall study, the blood glucose was measured in men, in the morning, 2h after a 50-g glucose load. Significant seasonal variation in mean blood glucose values occurred, with highest values in winter and lowest in spring (March–May, inclusive). However, there was no significant difference by season in the proportions exceeding the arbitrary cut-off levels of 7.8 and 11.1 mmol/l.

Taylor, R.; Ram, P.; Zimmet, P.; Raper, L.; Ringrose, H.

doi: 10.1007/BF00276971pmid: 6530053

125 27 27 6 6 Dr. R. Taylor P. Ram P. Zimmet L. R. Raper H. Ringrose WHO Collaborating Centre for the Epidemiology of Diabetes Mellitus Royal Southern Memorial Hospital Melbourne Australia South Pacific Commission Noumea, New Caledonia Colonial War Memorial Hospital Suva Fiji Health Commission of Victoria Melbourne Australia Summary In Fiji Melanesian and Indian men, prevalence of diabetes is more than twice as high in those graded as sedentary or undertaking light activity as in those classed as performing moderate or heavy exercise. This difference was present in both ethnic groups, and maintained when age, obesity, and urban/rural status were taken into account. It is concluded that, in the population under study, there is epidemiological evidence for the role of physical inactivity as an independent risk factor for Type 2 (non-insulin-dependent) diabetes.

Hillaire-Buys, D.; Ribes, G.; Blayac, J.; Loubatières-Mariani, M.

doi: 10.1007/BF00276972pmid: 6152237

125 27 27 6 6 D. Hillaire-Buys G. Ribes J. P. Blayac Professor M. M. Loubatières-Mariani Faculté de Médecine, Laboratoire de Pharmacologie et Pharmacodynamie, Equipe de Recherche Associée au CNRS no 786 Institut de Biologie Montpellier France Summary LN 5330 is a new benzothiadiazine which is a structural analogue of diazoxide. Its effects in vivo were studied on blood glucose levels and insulin, glucagon and somatostatin secretion in normal dogs, and in vitro on glucagon and insulin secretion from the isolated perfused rat pancreas. The results were compared with those obtained with diazoxide at equimolar dose or concentration. In the normal anaesthetized dog having a T-shaped catheter inserted in the pancreaticoduodenal vein, the infusion of LN 5330 (87.8 μmol/kg for 20 min) induced (1) a progressive increase in blood glucose levels, (2) a rapid decrease in insulin and somatostatin output rate, (3) an immediate increase in pancreatic glucagon secretion, and (4) a delayed decrease of arterial blood pressure. The equimolar dose of diazoxide provoked the same effects on blood glucose levels, insulin and somatostatin output, but a marked decrease in glucagon output and in arterial blood pressure. In the isolated rat pancreas perfused with 8.3 mmol/l glucose, the infusion of LN 5330 (440 μmol/l for 30 min) induced a drastic fall in insulin and a rapid and persistent increase in glucagon output. This stimulatory effect on glucagon secretion was not found with diazoxide at equimolar concentration. These findings show that LN 5330 is a substance which is distinct from diazoxide and interesting because of its double action: inhibition of insulin secretion and stimulation of glucagon secretion.

Wilson, G.; Patton, N.; McCord, J.; Mullins, D.; Mossman, B.

doi: 10.1007/BF00276973pmid: 6241574

125 27 27 6 6 Dr. G. L. Wilson N. J. Patton J. M. McCord D. W. Mullins B. T. Mossman Departments of Anatomy and Biochemistry University of South Alabama Mobile Department of Biochemistry University of Alabama in Birmingham Birmingham Alabama Department of Pathology University of Vermont Burlington Vermont USA Summary In studies to evaluate possible inhibitors of the B-cell toxin, streptozotocin, the superoxide scavenger, superoxide dismutase, did not prevent or reduce the toxic effects of streptozotocin as determined by loss of insulin secretion from rat pancreatic B cells in monolayer culture. However, 1,1-dimethyl urea, a scavenger of the hydroxyl radical, did afford significant protection. Both scavengers diminished the cytotoxic effects of alloxan. The inhibitors of poly (ADP-ribose) synthetase, 3-aminobenzamide and nicotinamide, also were effective in attenuating alloxan- and streptozotocin-induced B-cell toxicity. Tests of the hydroxyl-scavenging ability of the three streptozotocin antagonists revealed that 3-aminobenzamide, nicotinamide and 1,1-dimethyl urea were effective scavengers of this free radical. Conversely, 1,1-dimethyl urea, although not as potent as 3-aminobenzamide or nicotinamide, was found to inhibit poly (ADP-ribose) synthetase. These data indicate that these chemicals most likely attenuate alloxan-induced toxicity by scavenging the hydroxyl radical and diminish streptozotocin-induced toxicity by inactivation of the poly (ADP-ribose) system.

Ionescu-Tîrgovi¢te, C.; Mincu, I.; Simionescu, L.; Cheta, D.; Mirodon, Z.; Sântu, E.; Popa, E.; Bîrnea, A.

doi: 10.1007/BF00276974pmid: 6397385

125 27 27 6 6 Dr. C. Ionescu-Tîrgovi¢te I. Mincu L. Simionescu D. Cheta Z. Mirodon E. Sântu E. Popa A. Bîrnea Clinic of Nutrition and Metabolic Diseases Bucharest Romania Summary The disappearance rate of insulin antibodies was studied after cessation of insulin treatment which had been given for 3 months to 6 years in 42 Type 2 (non-insulin-dependent) diabetic patients. Insulin antibodies were measured before and 15 days after interruption of insulin treatment, and every 30 days until the disappearance of insulin antibodies. The mean ± SD value of insulin binding in the entire group before the interruption of insulin treatment was 32±14%. There was no relationship between the antibody level at that time and the duration of insulin treatment. However, the insulin antibody level was significantly higher in 17 diabetic patients on an insulin dose of >20 U/day ( p <0.02) than in 25 on an insulin dose of <20 U/day (39±13% versus 28±12%). A positive correlation was found between intial insulin binding and the time required for it to fall below 10% ( r = 0.74). Antibodies were absent 60 days after discontinuing insulin treatment in eight of ten subjects presenting with initial binding of <20%. In contrast, in only two of 12 patients with an initial binding of >40% were insulin antibodies detectable 150 days after discontinuation of insulin therapy. Disappearance of insulin antibodies sometimes took up to 1 year and occasionally even more than 2 years.