[Trial treatment of diabetic retinopathy by inhibition of pituitary somatotropin secretion with MAP].

The recent literature relating to the pathogenesis of diabetic retinopathy, with or without nephropaty, is critically reviewed. Particular attention is given to the Growth Hormone (GH) hypothesis. The various procedures of hypophysectomy are discussed, including the possible ways of suppressing growth hormone production or overproduction by drugs, and expecially by medroxyprogesterone acetate (MAP). Personal results obtained with long-term administration of MAP in deposit form on alternate days in 10 patients with advanced retinopathy are described. An icostant and rely significant suppression of the GH response to insulin-induced hypoglicemia was noted in 6 cases, showing that a complete pituitary inactivation had been achieved. Therefore, the modifications observed in the fundus picture (studied with retinal photographs according to the Hammersmith Hospital Standards) seem to have no relationship with such a condition. The features involved were Microaneurysms and Haemorrhages (HAEMS) and Exudates (EX);New Vessels (NV) and Retinitis Proliferans (RP) were unaffected. Subjective improvement is visual acuity appeared to be more frequent, with various possible explanations. MAP was without appreciable effect on the clinical and metabolic course of the diabetes, or on renal function in cases of concomitant nephropathy. In the light of these preliminary results, further investigations might seem to be justified.

PIP: The recent literature relating to the pathogenesis of diabetic retinopathy, with or without nephropathy, is critically reviewed. Particular attention is given to the (GH) growth hormone hypothesis. The various procedures of hypophysectomy are discussed including the possible ways of suppressing GH production or overproduction by drugs, especially with (MAP) medroxyprogesterone acetate. Personal results obtained with long-term administration of MAP in depot form on alternate days in 10 patients with advanced retinopathy are described. An inconstant and barely significant suppression of the GH response to insulin-induced hypoglycemia was noted in 6 cases showing that a complete pituitary inactivation had not been achieved. Therefore, the modifications observed in the fundus picture seem to have no relationship with such a condition. The features involved were Microaneurysms and Hemorrhages and Exudates. New vessels and retinitis proliterans were unaffected. Subjective improvement in visual acuity appeared to be more frequent with various possible explanations. MAP was without appreciable effect on the clinical and metabolic course of the diabetes or on renal function in cases of concomitant nephropathy. In light of these preliminary results, further investigation seems to be justified. (author's modified) (summary in ENG).

[Hyperglycemic hyperosmolar non-ketotic diabetic coma with prolonged insulin-resistnace and extremely high values of insulin-IgG-binding]. / Coma diabetico iperglicemico iperosmolare non-chetosico con relativa insulinoresistenza protratta e valori estremamente elevati di insulin-IgG-binding

The paper reports the occurrence - over a period of some days - of a hyperosmolar non ketotic coma, with prolonged relative insulin-resistnace in a micro- and macroangiopathic long term diabetic subject, after infection and minor surgery. The patient was on oral hypoglycemic treatment during the past 11 years; previously he had been treated with Protamin Zinc Insulin. The case is characterized by extremely high values of Insulin-IgG-binding (12 MU/ml), which still further increased to 20 mU/ml when an emergency insulin management was recommenced, perhaps as the result of an immunogenic booster effect. A diagram of underlying and precipitating conditions likely to lead to diabetic non-ketotic coma is presented. Exogenous anti-insulin immunitary factors are postulated as exceptional condidates for inclusion.

[Clinical experiences with monocomponent insulins]. / Esperienze cliniche con le insuline monocomponenti

The immunogenicity of conventional therapeutical insulin is discussed according to the concepts of Schlichtkrull: the formation of insulin antibodies is not attributable to the pure Sanger's insulin molecule, but to related protein impurities, present in all crystallized pig and ox insulin preparations. The terms of monocomponent insulin, highly purified insulin, and single peak insulin in defined and personal clinical results obtained with Novo Monocomponent Lente Insulin over a period of 3 years are presented. The Hein Christiansen's radioimmunoelectrophoretic method fo estimation of 125I-insulin IgG binding was used to determine insulin antibody levels. It was found that: 1) Newly detected insulin-dependent diabetics, never previously treated with insulin, do not produce insulin antibodies at a significant level; 2) Long-term insulin treated diabetics, transferred to monocomponent treatment, tend to reduce their antibody levels, if initially high, altough with transient recurrent peaks; 3) Stimulation of the immunocompetent system by intercurrent infection does not generally modify the immunological situation. Apart from immunological changes, satisfactory clinical results were observed in cases of high insulin requirement, insulin allergy, insulin lipoatrophy. Present practical indications for monocomponent insulin therapy (Actrapid-Lenta) are proposed.

[Evaluation of the antibody anti-insulin titer using Christiansen's radioimmunoelectrophoresis in clinical diabetology]. / Valutazione del titolo anticorpale anti-insulina colla tecnica radioimmunoelettroforetica di Christiansen in diabetologia clinica.

On the basis of personal experience concerning 2020 consecutive determinations, the radioimmunoelectrophoretic method of Christiansen for 125I-Insulin-Binding to IgG (= IB, significant limits = mU/ml) has been proved as a reliable tool for the evaluation of insulin antibody titer in clinical diabetology. After a critical review of the recent literature about insulin antibodies both without and after exogenous immunization, the following results are presented and discussed. 1) - In 163 diabetic subjects, never previously treated with insulin, the mean value of IB was X = 0,008 mUml (sigma = 0,023 . Sx = 0,002). 2) - In 221 longterm insulin-treated diabetics the mean value of IB was X = 1,50 mU/ml (sigma = 2,15 . Sx = 0,145). 3) -In 46 insulin-dependent diabetics, serial determinations of IB allowed to follow the insulin antibody production during a 5 years treatment with monocomponent insulin )Lente MC). No or slight antibody formation was observed in newly diagnosed patients, never previously treated with insulin. High antibody starting levels showed tendency to a gradual reduction, after switching from conventional insulin treatment to the monocomponent one. These modifications in the IB values have been studied in correlation with the clinical course of conditions possibly referred to an immunologic pathogenesis, such as: brittle diabetes, high insulin requirement, insulin allergy, insulin lipoatrophy, diabetic microangiopathy. No significant variations in IB values were observed after viral infections.