[Nocturnal continuous subcutaneous insulin infusion--a therapeutic possibility in labile type I diabetes under exceptional conditions]. / Die nächtliche kontinuierliche subkutane Insulininfusion--eine Therapiemöglichkeit des labilen Typ I-Diabetes in Ausnahmesituationen.

The whole-day continuous subcutaneous insulin infusion (CSII) with portable pumps in daily blood glucose autocontrol guarantees a more stabile and favourable glycaemia than multiple injections in labile type I diabetics. The success is mainly to be traced back to the continuous replacement of the basal secretion, particularly to the nocturnal fasting phase. In this study the effect on the glycaemia is investigated with exclusively nocturnal administration of the CSII under maintenance of multiple insulin injections during this day. In a group of 18 type I diabetics the nocturnal CSII in comparison to intermediate insulin administrations in the evening led to a significant improvement of glycaemia (p less than 0.01), in particular to the decrease of the fasting blood sugars (p less than 0.05). In two casuistic observations in comparison to all the other conventional methods for the compensation of the nocturnal glycaemia (depot insulin, nocturnal injection of normal insulin) the nocturnal CSII proved to be superior. Therefore, the nocturnal CSII is an--though more rarely to be used--alternative, which may be taken into consideration, of a whole-day CSII is temporarily unwished for.

36 months continuous subcutaneous insulin infusion (CSII) in insulin dependent diabetes (IDDM)--influence on early stages of retinopathy, nephropathy and neuropathy--psychological analysis.

UNLABELLED: In extremely unstable (brittle) IDDM patients (n = 11) the metabolic effect of long-term (36 months) CSII proved to be superior to conventional insulin treatment (CIT) (statistical twins, n = 11): HbA1 = 8.6 +/- 0.3 versus 10.4 +/- 0.4, MBG = 5.6 +/- 0.3 versus 8.5 +/- 0.8, M (80)- value = 23.6 +/- 0.6 versus 56.7 +/- 10.2, GCI) = 37.3 +/- 15.6 versus 132 +/- 24.2. In addition, in CSII patients the metabolic control was significantly better than intensified conventional insulin treatment (ICT) before. Retinal morphology improved under CSII in 1 eye, did not change in 10 eyes and deteriorated in 11 eyes. Under CIT retinal findings improved in none, did not change in 16 and deteriorated in 16 eyes. Deteriorations under CSII appeared more frequently during the first than during the second and third year of treatment and seemed to be a consequence of too strict metabolic control and/or too fast decrease of the glycemia at the beginning of CSII. During 36 months of CSII no deterioration but in one case normalization of microproteinuria was observed. Under CIT three cases changed from normal into microproteinuria. Reduced motor nerve conduction velocity (MCV) and/or sensory nerve conduction velocity (SCV) could be normalized in most cases under CSII, but respiratory heart arrhythmia (RHA) at rest could not. Most patients--if highly motivated before starting CSII--remained positively motivated for long-term pump therapy. IN CONCLUSION: Our experiences over three years demonstrate a positive effect of CSII on the metabolism as well as on the course of early stages of microangiopathy and neuropathy. A longer period of observations will be necessary to evaluate this, conclusively.

Results of treatment with continuous subcutaneous insulin infusion (CSII) in insulin-dependent (type I) diabetics.

10 labile insulin-dependent diabetic patients treated with CSII were followed up for 6 to 16 months under conditions of everyday life. The mean blood glucose (MBG), glycosylated haemoglobin (HbA1), motor nerve conduction velocity (MCV), and respiratory heart arrhythmia at rest (RHA) were investigated. A significant improvement of metabolic control was observed (MBG 8.03 +/- 1.40 vs 5.18 +/- 0.87 mmol/l, p less than 0.01; HbA1 10.7 +/- 1.3 vs 8.7 +/- 1.6%, p less than 0.05) in comparison with the control values under intensified conventional therapy. MCV increased gradually but the average RHA remained unchanged. The psychological examination employing a questionnaire reflects that all patients selected were highly motivated and that their positive attitudes were further stabilized during pump treatment. An average of three mild hypoglycaemic episodes occurred per month per patient; these were no more than under intensified conventional treatment. Other minor clinical and technical complications occurred at a total frequency of one per month per patient and did not achieve therapeutical relevance.

Diurnal rhythm of insulin sensitivity in subjects with normal and impaired glucose tolerance.

We studied the insulin sensitivity in 5 normal subjects and 5 subjects with impaired carbohydrate tolerance using the glucose controlled insulin infusion system (BIOSTATOR). During a fixed glucose infusion rate of 2 mg/kg b.w./min, the computer program was set to maintain the plasma glucose concentration at 4.44 mmol/l. The ratio of infused exogenous insulin to infused glucose served as a measure of insulin sensitivity. Calculating the average insulin glucose ratio for 24 hours, the mean values amounted to 3531 and 9319 ng/gm (p less than 0.01) in subjects with normal and impaired carbohydrate tolerance, respectively, indicating that insulin resistance is the main cause of decreased glucose utilization in the latter group. Circadian rhythms of insulin sensitivity occur in both groups in a similar fashion. The insulin sensitivity was higher in the afternoon (1200-1800) as compared to the night. Thus, diurnal variations in insulin sensitivity are independent of disturbances of glucose metabolism.

Portable insulin infusion devices: a new era in the treatment of insulin-dependent diabetics! Which patients should be treated?

The development of portable insulin infusion devices - in which the insulin dosage is programmed in advance (open loop system) are increasingly being used for long-term daily diabetes control. These pumps represent a new method for attaining significantly improved metabolic control (glycemia and glucose metabolites, HbA1, lipid and aminoacid metabolism) and an impressive influence on diabetic neuropathy, on general fitness and on quality of life of insulin-dependent diabetics. At least all insulin-dependent diabetics without noticeable residual insulin secretion should be treated by continuous subcutaneous insulin infusion (CSII) via portable pumps, that are 8 000-10 000 patients in the GDR and approximately 500 000 in the world. Considering special conditions (strict supervision by experienced medical staff, carefully drawn up adequate instructions, highly motivated and capable patients) we assume that at the present stage of technical development of the pumps infants, imbeciles and incooperatives should be excepted only.

[Transplantation of the endocrine pancreas]. / Transplantation des endokrinen Pankreas.

The transplantation of the endocrine pancreas has been investigated intensively as one way to optimize the therapy of diabetes mellitus. Starting with the free pancreas transplantation 1966 in diabetics, more recently research has been focused on transplantation of pancreatic islets or fetal pancreatic slices and the segmental pancreas transplantation. These forms of transplantation of the endocrine induced diabetes in various animals. Whereas the transplantation of a dispersed pancreatic preparation (islets or fetal pieces) is not connected with any acute or chronic alternation for the patient, the complication rate of the segmental pancreatic transplantation has to be reduced for a broader clinical application. In the case of islet transplantation the research efforts were concentrated on the improvement of tissue preparation and prolongation of the tissue survival.

Insulin responsiveness of adipose tissue from normal weight subjects with early diabetes.

In normal weight subjects, classified by a 2-h glucose infusion test as having normal (11), borderline (3) or pathological (9) carbohydrate tolerance (CHT), subcutaneous adipose tissue was removed under intracutaneous anesthesia by surgical biopsy. The biological responsiveness of isolated adipocytes as well as adipose tissue fragments measured as incorportion of (1-14C) glucose into CO2 or triglycerides was studied in the absence or presence of different insulin concentrations. In persons with normal CHT the insulin-stimulated (62.5 microU/ml) glucose conversion to CO2 by adipocytes as well as fat pads increased significantly up to 156 +/- 14% and 285 +/- 30%, respectively. Insulin enhanced the glucose incorporation into triglycerides up to 154 +/- 20% (fat cells) and 258 +/- 30% (fat pads) in adipose tissue from subjects displaying a normal CHT. Rates of glucose oxidation and triglyceride synthesis was markedly reduced in adipose tissue obtained from patients with borderline or pathological CHT. A significant positive relationship was found between glucose oxiation to CO2 and triglyceride production of fat cells and fat pads (r = 0.964 and 0.783, respectively). There was no correlation with responsiveness of adipose tissue to insulin and insulin secretion during glucose infusion test. The results indicate that sensitivity to insulin of target cells might be important for the development of carbohydrate intolerance also in normal weight subjects.

Regulation of pancreatic glucagon secretion during a continuous glucose infusion in early and overt diabetics.

The pancreatic glucagon (IRG) secretion pattern was studied during a 2 h glucose infusion test (12 mg/kg/min) in 21 controls as well as in 44 subjects showing different degrees of carbohydrate intolerance. The fasting IRG levels increased significantly from controls (98 +/- 7.6 pg/ml) to chemical (144 +/- 9 pg/ml) and mild maturity-onset-type diabetics (166 +/- 12.2 pg/ml). During artificial hyperglycaemia the glucagon concentrations decreased slightly in all groups, but they remained at a higher level in early and overt diabetics). The molar IRI-IRG ratios have been found to be diminished in patients displaying a disturbed carbohydrate tolerance. There was not any correlation between insulin and glucagon concentrations in the blood. The findings suggest that abnormalities of alpha cell function may be present in early and overt diabetes independent of beta cell responsiveness. The causal relationship of A and B cell function in glucose intolerant subjects has to be cleared in follow-up studies.

[Obesity as a metabolic risk factor]. / Fettsucht als metabolischer Risikofaktor.

On the basis of the results of clinico-experimental examinations and of animal experiments the importance of obesity as metabolic factor of risk is confirmed and hereby the diabetes mellitus as well as cardiovascular effects are particularly taken into consideration. Conclusions are made relevant to practice and it is particularly referred to the central position of the B-cells for the pathogenesis of diabetes as well as to prophylactic and early therapeutic measures.

[Carbohydrate tolerance and behavior of insulin in the glucose infusion test in persons with normal weight with prediabetic suspicion]. / Kohlenhydrattoleranz und Insulinverhalten im Glukoseinfusionstest bei normgewichtigen Personen mit Protodiabetesverdacht

In altogether 289 persons with normal weight with suspicion of the existence of a prestage of diabetes the 2 hour's glucose infusion test was carried out. In these cases 61% of the test persons showed a normal, 8% a critical, 26% a pathological and 5% a manifest diabetic metabolic condition. A reduction of the initial and late phase of the insulin secretion provable with deterioration of the carbohydrate tolerance must be regarded as cause of metabolic disturbances. The lack of a significant relation between diabetic heredofamiliality and carbohydrate tolerance indirectly refers to the importance of the environmental factors which on the basis of a genetic defect have a decisive influence of the morbidity caused by diabetes. The reduction of the initial phase which is provable already in potential diabetes, particularly clearly it is to be demonstrated in pathological and manifest diabetic metabolic situation, may be regarded as an early symptom of diabetes. Carbohydrate tolerance and preparation of insulin were reduced in decenniums of older age.

Glucose-induced insulin secretion and insulin sensitivity of peripheric organs of Egyptian sand rats before manifestation of diabetes.

In Egyptian sand rats (Psammomys obesus) fed with native food and a low caloric vegetable diet after capture it was possible to study endocrinologic and metabolic changes of the early stages during the progression to diabetes. According to body weight gain and fasting blood glucose the animals were differentiated into two groups classified as basic and protodiabetic group, respectively. Isolated pancreatic islets as well as the perfused pancreases of sand rats responded to low concentrations of glucose with high insulin release during early stages of the development to diabetes. Changes in the insulin content of the islets could not be detected at this time although in the B-cells of the protodiabetic animals a degranulation was visible. During these early stages of the development to diabetes the in vitro insulin action on glucose utilization in soleus muscle and especially in epididymal fat pads as well as the basal glucose metabolism in adipose tissue were low. This strikingly reduced utilization of glucose by adipose and muscle tissues may be a factor which challenges the B-cell.

[Relations between portal and peripheral venous insulin, proinsulin and glucagon concentrations after oral glucose in man]. / Beziehungen zwischen den portalen und peripher-venösen Insulin-, Proinsulin- und Glukagonkonzentrationen nach oraler Glukosegabe beim Menschen

During cholecystectomy a catheter was inserted into the V. porta via V. umbilicalis. 7 or 8 days later an oral glucose tolerance test was performed (100 g). Blood glucose, insulin (IRI), proinsulin-like material (PLM), and pancreatic glucagon (IRG) concentrations were determined in portal as well as in peripheral venous blood. 5 out of 6 patients showed a disturbed carbohydrate tolerance in comparison to 53 healthy subjects. The IRI increased promptly after the oral glucose load. The portal IRI-concentrations are significantly enhanced in comparison to the peripheral levels, but between both a positive correlation exists (r = 0.9447; p less than 0.01). PLM was slightly increased in the first 10 minutes. The basal IRG levels were not enhanced. Significant differences between the portal and peripheral IRG concentrations could not be observed. The correlation coefficient was 0.8902. Thus, the peripheral venous concentrations of IRI, PLM and IRG can be used as a diagnostic tool of pancreatic hormone secretion in man.