[Hypoglycemia caused by insulinoma in diabetes mellitus]. / Hypoglykämie durch Insulinom bei Diabetes mellitus.

An hyperglycaemic metabolic state disappeared and spontaneous hypoglycaemia occurred in a 58-year-old woman with non-insulin-dependent obese type II diabetes. Abnormal absence of the hunger response with provoked hypoglycaemia, increased serum insulin concentrations and reduced blood glucose/insulin ratio led to the diagnosis of pathological hyperinsulinism, which was found to be due to an insulinoma of the tail of the pancreas. After its excision the patient's carbohydrate metabolism returned to a mild type II diabetic state and there were no further hypoglycaemic attacks.

Prolonged plasma half-life of insulin in patients with a genetic defect of high affinity binding sites.

Plasma clearance of endogenous and intravenously administered insulin was studied in three sibs with severe insulin resistance secondary to an affinity defect of their insulin receptors, and in five healthy controls. Intravenous infusion of somatostatin was used to inhibit the insulin secretion. 0.3 U of insulin/kg body weight was administered as an intravenous bolus. Plasma glucose, immunoreactive insulin and C-peptide were determined subsequently at constant intervals. We found a prolonged plasma half-life of insulin in the three patients, being 33.5 +/- 11.8 min vs 8.2 +/- 2.2 min in controls, P less than 0.002, but a normal half-life of C-peptide. The result indicates, that the plasma insulin clearance is predominantly mediated by intact insulin receptors. We conclude, that insulin has a prolonged half-life in all patients with insulin resistance secondary to an impaired receptor function.

[Successful therapy of recurrent hypoglycemias by surgical removal of a malignant hemangiopericytoma]. / Erfolgreiche Therapie rezidivierender Hypoglykämien durch operative Entfernung eines malignen Hämangioperizytoms.

Tumor growth in a 72-year-old male patient with malignant haemangiopericytoma in the left hemithorax could be followed radiologically for 4 years before symptoms of recurrent hypoglycaemia appeared. The endogenous insulin level in serum was maximally and serum IGF-1 and IGF-2 markedly reduced. An intravenous arginine load test showed a normal stimulation capacity of the pancreatic glucagon secretion but not that of insulin. After resection of the tumor, blood sugar metabolism was completely normalised. The insulin level, IGF-1 and IGF-2 in serum returned to normal.

Circulating insulin antibodies during therapy with highly purified neutrally buffered insulins including desphe insulins. Report of a prospective study with 40 cases.

Circulating insulin binding capacity was studied for 10 to 24 months in forty diabetic patients who were being treated with insulin for the first time. They received either neutral highly purified pork insulin, bovine or porcine desphe insulin containing formulations, semisynthetic human insulin, or "conventional" acid chromatographed bovine surfen insulin over the entire duration of the study. In only 6 of the 23 patients on pork insulin, porcine desphe insulin, or human insulin were minimal antibody concentrations (less than or equal to 2 IU/l) observed. The bovine desphe insulin containing beef insulin, was markedly more immunogenic: only 3 out of 12 patients did not produce any antibodies. All five patients treated with bovine surfen insulin reacted with a strong antibody formation, which was, on average, six times as high as that in the patients on bovine desphe insulin (approximately 90 vs 14 IU/l). According to these results, bovine desphe insulins should be considered more valuable in insulin therapy than formulations of unmodified beef or of mixed beef/pork insulins.

[Cardiac impulse generation and conduction in patients with long-term insulin-dependent diabetes mellitus]. / Untersuchungen von Impulsbildung und Erregungsleitung des Herzens bei Patienten mit langjährigem insulinpflichtigem Diabetes mellitus.

In a selected group of 14 diabetic patients (seven women, seven men) with an average age of 38 years, average duration of diabetes 20 years, all with end-organ manifestations but without hypertension or previous myocardial infarct, His bundle electrography at resting conditions and during programmed electrical stimulation was carried out to determine whether diabetes mellitus, alone, affects meaningful disturbances of impulse generation and conduction. The sinus node recovery time, conduction time through the atrium, the AV-node and the His-Purkinje system as well as the effective and functional refractory periods of the atrium and AV-node were determined. At rest, all patients had normal findings. During atrial stimulation, two patients were found to have intraatrial conduction disturbances and one patient had impaired AV-nodal conduction reserve; the latter had diminished 1:1 conduction through the AV-node during atrial stimulation. In general, however, diabetes mellitus, alone, does not appear to be of clinically-relevant pathologic importance for the development of rhythm disturbances at the levels of the sinus node and/or the AV-node and His bundle system.

Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.

We describe three siblings with a mild diabetes mellitus in combination with acanthosis nigricans and multiple minor physical abnormalities. Fasting plasma insulin was elevated up to 100-fold as compared with normal values, and the diabetes was classified as insulin resistant. Insulin-binding studies on erythrocytes, monocytes, and cultured fibroblasts disclosed an abnormally reduced binding capacity, as compared with that of healthy controls, which was most prominent at low concentrations of insulin. Scatchard analysis on erythrocytes of the three patients revealed a normal number of total insulin-binding sites per cell, but a complete lack of insulin binding to the high-affinity receptor component. The findings are consistent with the assumption of two genetically distinct types of insulin receptors.

The syndrome of diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities (DIDMOAD-syndrome). Two affected sibs and a short review of the literature (98 cases).

We describe two sibs with DIDMOAD-Syndrome, a 19-year-old girl with diabetes mellitus (type I), optic atrophy, inner-ear deafness, and atonia of the urinary tract, and her 5-year-old brother with diabetes mellitus (type I) and optic atrophy. Studies of red blood cell insulin receptors revealed a normal number of receptors per cell and normal affinity to insulin. The syndrome represents an autosomal recessively inherited type of diabetes mellitus, which remains often undiagnozed since most of the symptoms except diabetes mellitus and optic atrophy occur with varying expressivity. An atonia of the efferent urinary tract often with fatal complications is present in 46% of all patients with this syndrome reported in the literature and is unfortunately not included in the acronym DIDMOAD.

[On C-peptide and some other parameters in children with insulin dependent diabetes mellitus (author's transl)]. / Insulinrestsekretion (C-Peptid) und einige andere Parameter für den Langzeitverlauf bei Patienten mit insulinbedürftigem Diabetes mellitus.

C-peptide and some other parameters have been evaluated in 62 patients (31 male, 31 female) with insulin dependent diabetes mellitus in respect to quality of diabetic control. C-peptide was negatively correlated to duration of diabetes as was duration of initial remission with insulin requirements. Duration of initial remission was correlated positively to quality of diabetic control. The correlations of C-peptide with quality of diabetic control, insulin requirements and duration of initial remission were statistically not significant; insulin requirements and quality of diabetic control were not correlated significantly. From the results it is concluded that for the quality of diabetic control and hence the long-term course in patients with insulin dependent diabetes mellitus the duration of initial remission as a result of the quality of initial treatment is of the utmost importance.

Chlorpropamide-alcohol flushing is not useful for individual genetic counseling of diabetic patients.

The presence or absence of chlorpropamide-alcohol flushing (CPAF) was not correlated with the classification of diabetes. Five out of twelve patients with juvenile-onset diabetes (JOD) flushed and three out of four patients with maturity-onset diabetes in young people (MODY) did not flush. Consequently, CPAF cannot be used for individual genetic counseling in diabetes mellitus.

[Pancreatic glucagon and the pathogenesis of diabetes mellitus (author's transl)]. / Pankreasglucagon und Pathogenese des Diabetes mellitus.

Eleven patients who had had total pancreatic resection had hyperglycaemia (16.8 +/- 7.7 mmol/1 corresponding to 3.02 +/- 1.38 g/l) after fasting for 14 or 36 hours. After arginine stimulation there was no evidence for pancreatic glucagon. These findings indicate that (1) in man there are no sites of pancreatic glucagon production outside of the (resected) pancreas; (2) marked hyperglycaemia may occur without glucagon.