[Therapy of diabetic polyneuropathy].
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Biomedical subjects
Publications and source records attributed to F A Gries.
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The influence of hyperglycemia on calmodulin-stimulated Ca2+-Mg2+-ATPase activity was studied in 20 diabetic subjects. A clear inverse relationship between short-term hyperglycemia as well as chronic hyperglycemia and calmodulin-stimulated Ca2+-Mg2+-ATPase activity could be demonstrated. Such a relationship could not be shown for basal enzyme activity.
Ninety poorly controlled C-peptide negative type 1 (insulin-dependent) diabetic patients with chronic complications were allocated to intensified insulin treatment with either continuous subcutaneous insulin infusion or multiple insulin injections; 83 were studied over 1 year (seven patients dropped out of the study). Peripheral nerve function was assessed by clinical examination, malleolar vibration perception threshold, and motor and sensory nerve conduction velocities (MNCV; SNCV) in the median, ulnar, peroneal, and sural nerves. In order to assess the effect of metabolic control on peripheral nerve function, the results in patients with normal mean HbA1 levels during months 3-12 of the study less than 8.6% (tight control (tc); n = 50) were compared with those with abnormal mean HbA1 greater than or equal to 8.6% (poor control (pc); n = 33). Mean blood glucose was significantly higher in pc than in tc at months 2-9 and 11 (P less than 0.05). In pc median and ulnar SNCV were significantly lower at 6 and 12 months, and ulnar and peroneal MNCV at 12 months than in tc (P less than 0.05). No significant differences between the groups were observed for median MNCV, sural SNCV, and vibration sensation. Further analysis revealed that in well-controlled patients who showed abnormal peripheral nerve tests at baseline, median, and ulnar MNCV and SNCV but not peroneal MNCV, sural SNCV, and vibration sensation were significantly improved after 12 months as compared with poorly controlled patients with initially abnormal tests (P less than 0.05). There were no differences in nerve function between well- and poorly-controlled patients who had normal nerve tests at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Formation of a hemostatic plug is triggered by platelets. Platelet function (e.g. adhesion, aggregation) depends essentially on membrane bound receptor proteins. Conventional chromatographic analysis of these glycoprotein macromolecules is difficult and not appropriate for diagnostic routine. In combination of cytoflowmetric single cell analysis with monoclonal staining we developed a bio-assay for qualitative and semi-quantitative analysis of glycoprotein IB and IIB/IIIA on vital fixed platelets. The expression of these molecules was evaluated in 20 healthy volunteers. The assay offers for the first time the possibility of screening the expression of receptor proteins on platelet membranes, which are related to indicate either a functional lack in bleeding disorders or a prethrombotic state due to an enhanced functional potential in high risk patients.
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The prevalence of islet cell antibodies in children with Type 1 (insulin-dependent) diabetes was determined in a cohort of 678 children. The natural course of islet cell antibodies was followed in 375 children at 1 year, 252 and 135 children after 2 and 3 years respectively. Islet cell antibodies were determined by indirect immunofluorescence on cryostat sections of human pancreas. At diagnosis of diabetes 85% of the children had detectable islet cell antibodies (mean titre 10.4). After 3 years 62% of the children were still islet cell antibody positive (mean titre 2.9) indicating a greater persistence of islet cell antibodies than described in earlier studies. In this large cohort a significant correlation between islet cell antibody prevalence or persistence and sex, age or HLA-DR type was not observed except for a faster loss of islet cell antibodies in very young boys and in patients lacking HLA-DR types 3 and 4. Complement fixing islet cell antibodies correlated with high titre islet cell antibodies. Greater persistence of islet cell antibodies was seen for cases with high antibody titre and in children with diagnosis of diabetes during the first half of the year.
The aim of this study was to examine whether therapeutical doses of nitrendipine influence platelet function. In eight healthy subjects, the platelet aggregation response to collagen in whole blood and platelet-rich plasma (PRP) was monitored over 12 h after single administration of 40 mg nitrendipine given orally and was strongly inhibited between 60-83% (0.3 microgram/ml collagen) versus baseline at the third and fourth hour. Stimulated thromboxane formation from exogeneous arachidonic acid decreased almost continuously, with lowest levels at the 12th hour. Basal thromboxane remained below 25 pg/ml, but platelet factor 4 increased to more than twice the baseline level in the fourth hour, presumably reflecting adrenergic counterregulation of hypotensive effects. These preliminary data show that therapeutic drug concentrations of nitrendipine inhibit platelet function. Therefore, calcium channel blockers may be of therapeutical value in the treatment of prethrombotic states with primary platelet hyperactivity as present, for example, in diabetes mellitus.
Non-insulin-dependent diabetes mellitus (NIDDM) is a very common disorder, but less attention is paid to it than to the more dramatic but less prevalent insulin-dependent diabetes. The majority of patients receive their care from primary health care physicians or doctors without particular training in diabetes. Care is highly variable and often inadequate. In the USA this problem has been tackled by promoting a national education programme involving extensive use of television together with written guidelines for management. These latter have been looked at with interest by many diabetologists in Europe, but it has been felt that the guidelines were not entirely suitable for European practice. As a result an initiative was taken to generate more suitable materials for European use. Diabetologists from 14 European countries, representing the European NIDDM Policy Group (EUR-NIDDM-PG) therefore met in Amsterdam in 1986 with the blessing of the Council of the European Region of the IDF. The aims were first to establish whether a concensus view on management of non-insulin-dependent diabetes could be achieved, and if this was possible then to produce written materials for use in the care of people with non-insulin-dependent diabetes aimed particularly at the primary health care sector and the general physician. A remarkable degree of concensus was reached considering the different backgrounds and specialties represented by the group. Discussions were lengthy but constructive and were pervaded by a determination to improve care for such patients in Europe. The first output from the group is the short concensus document which follows.(ABSTRACT TRUNCATED AT 250 WORDS)
Small and large fibre function was studied in 40 non-ketotic, newly diagnosed Type 1 diabetic patients and 48 age-matched controls, using 12 quantitative tests for assessment of cutaneous sensation. Patients were aged 10-39 years and had been treated with insulin for 4-31 days. Thermal discrimination (foot), warm and cold thermal perception (thenar eminence and foot), and heat and cold pain perception thresholds (thenar eminence) were significantly elevated in the patients as compared with the controls (p less than 0.05 to p less than 0.001). No significant differences in thermal discrimination (thenar), heat and cold pain perception (foot), and metacarpal as well as malleolar vibration perception thresholds were noted between the groups. The rates of abnormalities among the individual tests ranged from 0% to 27.5%, being lowest for vibration perception and highest for thermal perception thresholds after cold stimuli. The results in nine of 12 tests correlated significantly with age, but only two were related to HbA1c. Thus, sensory neural functions transmitted by small fibres, but not those transmitted by large fibres, were impaired in newly diagnosed Type 1 diabetics after the correction of initial ketosis and hyperglycaemia. Cooling perception tests were most sensitive in detecting abnormality. An age-related involvement of different small fibre functions was present in these patients.
IgG proinsulin autoantibodies (IgG-PAAs) have been found in a fraction of sera from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) before onset of insulin treatment. Only sera lacking insulin antibodies have been analyzed, to avoid interference. Competitive inhibition studies provide specificity for human proinsulin but not for insulin. IgG-PAAs largely cross-react with human C-peptide. Precursors of insulin thus are involved in the immune process of IDDM.
Despite the wide distribution of devices for self-monitoring of blood glucose (SMBG), there is no internationally accepted agreement on a standardized procedure for their evaluation. This is due to incomplete or even inappropriate technical evaluation and to inadequate evaluation criteria for their clinical acceptability. To provide adequate information on the performance of these devices over the whole clinically relevant range for SMBG (30-350 mg/dl), a standardized test procedure has been established for technical (accuracy, precision, and total deviation) and clinical (acceptance analysis) evaluation. To demonstrate the potency of this new approach, the following SMBG devices and test strips were evaluated: Chemstrip bG batch (n = 10), Glucostix batch (n = 2), Accu-Check II (n = 5), Diascan (n = 5), Diascan strip batch (n = 4), Glucocheck SC (n = 4), and Glucometer II (n = 4). The devices and test strips were examined by trained technicians, and in addition, 1 Chemstrip bG batch and 2 Accu-Check II meters were examined by 10 and 5 trained diabetic patients, respectively. Even the best-performing device did not achieve the American Diabetes Association's goal that SMBG measurements should be within 15% of the reference value. Instead, the maximal total deviation within the clinically relevant blood glucose range reached values that equalled deviations from the reference value between 16 and 108%. Three of 36 devices were classified as good, 29 as acceptable, and 4 as unacceptable for clinical use. In conclusion, this new approach to the technical and clinical evaluation of devices for SMBG is easy to perform and provides more realistic and comparable information for clinical use and approval than commonly used methods.
Somatic and autonomic nerve function was assessed by motor and sensory nerve conduction velocities (MNCV; SNCV), beat-to-beat variation at rest, speed of pupillary dilation, and pupillary latency time in 35 newly diagnosed type 1 diabetic patients aged 12-36 years. The nerve function tests were performed 18 +/- 2 (mean +/- SEM) days after the correction of initial ketosis and hyperglycaemia and again after 3 and 12 months of insulin therapy. Mean HbA1 levels of months 3 and 12 within the normal range less than 8.6% (mean: 7.2 +/- 0.2%) were observed in 24 patients (group 1) and greater than or equal to 8.6% (mean: 10.1 +/- 0.6%) in 11 patients (group 2). Group 1 showed no significant changes from baseline in the mean nerve conduction and autonomic functions after 3 and 12 months. In group 2 there was no change until three months, however, at 12 months there was a significant decrease in mean MNCV in the median, ulnar and peroneal nerves (p less than 0.05) and in mean SNCV in the median (p less than 0.05) and sural nerves (p less than 0.01), when compared to the baseline values. The autonomic function tests remained unchanged. No patient had symptoms of neuropathy during the period studied. These findings suggest that the deterioration of motor and sensory nerve conduction precedes that of cardiac and pupillary autonomic function in poorly controlled asymptomatic type 1 diabetic patients during the first year of the disease. Effective glycaemic control prevented progression of subclinical neuropathy, but did not reverse abnormalities which were present at diagnosis.
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To test whether proinsulin pretreatment can increase insulin effects, we studied the glucose lowering effect of insulin given intravenously as a bolus (9 mU/kg) following a two hour infusion of proinsulin (3 micrograms/kg body weight.h) in 11 healthy volunteers. Insulin was given directly after proinsulin infusion and two hours later. On a control day dilution medium has been infused only. The proinsulin dose chosen was able to reduce blood glucose significantly (from 4.30 to 3.81 mmol/l, P less than 0.05) without leading to increases in counterregulatory hormones. There were no significant changes in glucagon, growth hormone, adrenaline and noradrenaline, while cortisol showed a decline according to its diurnal rhythm during proinsulin infusion and control. Free fatty acids and glycerol as indicators of fat metabolism were reduced by 28.0% and 54.9% respectively, compared to reduction by 16.0% and 23.4% during control. Insulin injection directly after proinsulin infusion decreased blood glucose from 3.81 to 2.52 mmol/l. The decrease during control was from 4.38 to 2.98 mmol/l. Two hours after proinsulin infusion, blood glucose was decreased by insulin injection from 4.09 to 2.98 mmol/l, compared to a decrease from 4.08 to 3.19 mmol/l during control. No statistical significant effect of the preceding proinsulin infusion on insulin action could be demonstrated. Proinsulin seems to have no specific effect on either glucose or fat metabolism.
In 158 type 1 diabetic patients the relations between insulin antibodies and total insulin and between total insulin and insulin requirement, mean blood glucose, post-prandial change in blood glucose, mean deviation factor of blood glucose, M-value and frequency of hypoglycemias were investigated. Forty-eight patients were antibody negative (antibody level less than or equal to 0.4%) and 110 patients had various levels of insulin antibodies and elevated levels of total insulin, but not of free insulin. After having made all necessary efforts to stabilize metabolism, parameters of metabolic control were determined. No effect of the elevated total insulin levels in patients with insulin antibodies could be demonstrated on insulin requirement, mean blood glucose, postprandial rise in blood glucose, mean deviation factor of blood glucose and M-value. The efforts needed to reach acceptable blood glucose levels were not greater in patients with elevated total insulin. The frequency of hypoglycemias during the night was increased in patients with total insulin levels higher than 2 mmol/l which, although not statistically significant, may be of clinical relevance.
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