Controlled study comparing treatment with monocomponent insulin and conventional insulin in patients with lipoatrophy.

Twenty-one patients with evident lipoatrophy treated with conventional (Conv.) insulin were either allocated to continuation of treatment with previously used insulin (Conv. group, n = 10) or were transferred to Lente MC (monocomponent) insulin with or without supplementary Actrapid MC insulin (MC group, n = 11). On entry and after 3, 6 and 12 months of follow-up, serum insulin-, pancreatic polypeptide- and proinsulin-binding IgGs were determined by radioimmunoelectrophoresis according to the method of Christiansen. Prior to determination of proinsulin-binding IgG, the insulin-binding IgG was removed by means of sepharose-bound insulin according to the method of Heding. In both groups a slight decrease in the titer of insulin-binding IgG was observed: in the Conv. group from 5.33 +/- 0.92 (SEM) to 4.66 +/- 1.17 mU/ml after 12 months, and in the MC group from 3.22 +/- 0.64 to 2.66 +/- 0.46 mU/ml, respectively. Due to the small number of patients with pancreatic polypeptide antibody titers above the detection limit no statistical evaluation was carried out. The level of serum proinsulin-binding IgG decreased in the MC group only (from 9.3 +/- 2.2 to 1.9 +/- 0.6 ng/ml after 12 months), and even showed a slight increase in the Conv. group (the respective titers were: 14.0 +/- 4.6 and 14.9 +/- 4.6 ng/ml). In the MC group 10 patients (91%) showed improvement and 7 (64%) complete regression of their lipoatrophy corresponding to 6 (60%) and 2 (20%) in the Conv. group. This finding suggests a possible role of proinsulin-binding antibodies in the pathogenesis of insulin lipoatrophy.

[Immunogenicity of semisynthetic human insulin Novo--five year prospective studies]. / Immunogennosc insuliny ludzkiej pólsyntetycznej Novo--5-letnie badania prospektywne.

The aim of the study was to compare the immunogenicity of semisynthetic human and porcine monocomponent (MC) insulin Novo during--5-year observation. Thirty-one diabetic patients, never previously treated with insulin were randomly allocated to treatment with one of the two coded insulin preparations in a double blind trial. 15 patients aged 20-58 years (mean age--36 years) were treated with human insulin and 16 diabetics aged 19-61 years (mean age--34 years) with MC pork insulin. The insulin was injected twice a day (Actrapid plus Monotard). Serum insulin-binding antibodies were determined according to Christiansen (radioimmunoelectrophoretic method). The development of insulin-binding antibodies during the first year of observation was more rapid in patients treated with MC pork insulin but thereafter it was similar in the two studied groups. After 5 years of treatment with human insulin serum insulin-binding antibodies were found in 14 patients. The level of antibodies was very low (< 0.130 mU/ml) in 5 subjects, low (0.171-0.401 mU/ml) in 6 patients and relatively high (0.885; 1.186; 5, 162 mU/ml) in 3 patients. In the group of diabetics treated with MC pork insulin after 5 years of observation serum insulin-binding antibodies were found in 12 patients. The level of antibodies was low (0.131-0.576 mU/ml) in 9 subjects and relatively high (1.034; 3.954; 5.639 mU/ml) in 3 patients. The results obtained after 2-5 years of the study did not differ significantly (Wilcoxon's test, p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoglycemia: a major problem in the management of diabetes in the elderly.

The aim of this study was to evaluate the incidence and causes of hypoglycemia requiring hospitalization of diabetic patients treated with insulin or oral antidiabetic agents. From 1975 to 1989, 20,978 patients were treated in the Department of Gastroenterology and Metabolic Diseases of the Warsaw Medical School; review of their records disclosed that severe hypoglycemia was the cause of admission in 236 cases (1.12%). Two hundred patients (74 older than 60 years) were treated with insulin and 36 (28 older than 60 years) with oral agents. The most frequent cause of hypoglycemia was dietetic error (123 cases), followed by excessive physical effort (55 cases), error in the dose of hypoglycemic drug (22 cases), and alcohol abuse (13 cases). Hypoglycemia was the cause of death in 13 patients (8 aged over 60 years). In another 24 patients (17 aged over 60 years), exacerbation of ischemic heart disease was observed. Serious injuries with bone fracture were experienced by 11 patients (7 aged over 60 years). We conclude that hypoglycemia is still a serious risk for the life and health of diabetic patients treated with insulin or oral agents, especially those in advanced age. For this latter group of patients, more liberal criteria of metabolic control seem to be justified.

[Sneddon syndrome]. / Zespóll sneddona.

There is presented a case a 42 year old woman, who was admitted to the Department of Internal Diseases, the Institute of Dentistry, Medical Academy in Warsaw, with suspected bacterial endocarditis. Two episodes which indicate a lesion in the central nervous system (as right side hemiparesis and mixed aphasia) in the patients with valvular heart disease, were the basis of this suspicion. Bacterial endocarditis was not confirmed during hospitalisation. Diagnosis of Sneddon's syndrome was established based on skin lesion of livedo reticulatis type with typical picture in skin biopsy and on the lesions in the central nervous system confirmed by MRI. Moreover the patients had arterial hypertension and Raynaud's syndrome. We presented the diagnostic difficulties of Sneddon's syndrome, a course of the disease, the factors, which affect its prognosis and attempts to treat this syndrome based on this case.

[Inhibition of growth hormone (GH) response to GHRH in diabetes mellitus type 1 after blockade of the cholinergic system with pirenzepine]. / Zahamowanie odpowiedzi hormonu wzrostu (GH) na GHRH w cukrzycy typu 1 po blokadze ukladu cholinergicznego pirenzepina.

The effect of pirenzepine, a peripheric cholinergic antagonist, on GHRH-induced GH secretion was studied in 10 type I diabetic subjects and 8 healthy controls. GH response was significantly greater in diabetics than in the healthy controls (p < 0.02) with peak values of 59.6 and 15.9 ng/ml, respectively. Pirenzepine 20 mg in given 15 min before GHRH inhibited GH response in both groups. In diabetics GH response calculated as area under curve (AUC) was inhibited from 3666 to 260 ng/ml. min (p < 0.001) and in the controls from 831 to 255 ng/ml. min (p < 0.05). The great efficacy of pirenzepine in inhibiting GH hypersecretion in type I diabetes may find a clinical application in future.

Serum insulin, pancreatic glucagon and growth hormone levels in response to intravenous infusion of L-arginine in patients with recently detected juvenile diabetes.

The secretion of insulin, glucagon and growth hormone was determined in the serum of patients with recently diagnosed juvenile-type diabetes (10 patients) during stimulation by intravenous infusion of L-arginine and was compared with the results found in a group of five healthy persons. The value of the insulinemia was significantly lower in the diabetics as compared with the healthy controls. Serum glucagon levels were higher in all diabetics when fasting and after L-arginine administration as compared with the controls but a significant difference was observed only at the peck of secretion (5 min after L-arginine administration). Growth hormone concentration was slightly higher in the diabetics after secretory stimulation than in the controls, particularly at the peak of secretion (30 and 45 min) but the difference was statistically no significant.

Exaggerated growth hormone response to growth hormone-releasing hormone in type I diabetes mellitus.

Excessive GH response to various stimuli has been frequently described in diabetes mellitus. We studied the GH response to a synthetic GHRH in a group of 16 non-obese Type I diabetic patients. GHRH (1-44) given as iv bolus at a dose of 50 micrograms induced a markedly greater GH response in the diabetic than in the normal subjects with peak values of 39.5 and 14.7 micrograms/l, respectively, and the differences were significant from 15 to 60 min. Peak GH level was 44.6 micrograms/l in diabetic patients without retinopathy and 34.2 micrograms/l in patients with retinopathy, but the difference was not significant. Peak GH levels did not correlate with metabolic control of disease estimated by basal glucose and HbA1 levels nor with age, weight of the patients, and duration of the disease. It is concluded that Type I diabetic patients show an exaggerated GH response to GHRH and this response does not correlate with the metabolic control of diabetes.

[Increased urinary excretion of transforming growth factor beta and interleukin-6 in patients with diabetic nephropathy]. / Wzrost wydzielania do moczu transformujacego czynnika wzrostu beta i interleukiny-6 w przebiegu nefropatii cukrzycowej.

The purpose of the study was to assess TGF-beta and IL-6 urinary excretion (measured with EIA) in 12 IDDM patients (7 F, 5 M, age 20-49 yrs, mean = 33.08) with albuminuria or microalbuminuria. Control group consists of 27 IDDM patients (12 F, 15 M, age 24-59 yrs. mean = 39.5) without albuminuria or microalbuminuria. Urinary excretion of IL-6 was significantly higher (p < 0.05) in IDDM patients with albuminuria (mean = 7.43 +/- 8.29 pg/mg creatinine) than in control group (mean = 3.74 +/- 2.64 pg/mg creatinine). Urinary excretion of TGF-beta was also higher (but not significantly in IDDM patients with albuminuria or microalbuminuria (mean = 42.0 +/- 30.0 pg/mg creatinine) than in control group (mean = 27.0 +/- 20.0 pg/mg creatinine). The data indicate that IL-6 and TGF-beta could be involved in the development of diabetic nephropathy.

[Comparative assessment of the biological effects of semisynthetic human insulin and porcine insulin in healthy subjects]. / Porównanie dzialania biologicznego pólsyntetycznej insulny ludzkeij i insuliny wieprzowej u ludzi zdrowych.

The purpose of the study was the assessment of certain biological effects of semisynthetic human insulin compared with the presently used monocomponent preparations of porcine insulin made by the same producer. The study was carried out in a group of 10 healthy subjects (7 men and 3 women) twice: during a loading test with porcine insulin, and then during a similar test with human insulin. Both insulins were administered intravenously in doses of 0.075 units/kg body weight The physiological reactions associated with hypoglycaemia were noted, including subjective experiences and hormonal responses, among them those of glucagon, growth hormone, prolactin, adrenaline, noradrenaline and C-peptide. Semisynthetic human insulin administered intravenously was found to exert an identical hypoglycaemic effect as porcine insulin. However, it was observed that the action of porcine insulin was associated with more pronounced symptoms and more intense physiological reactions (tachycardia, body temperature fall) and a striking increase of prolactinaemia, in relation to semisynthetic human insulin.

The effect of phenformin on amino acid-induced insulin secretion in diabetics.

Twenty-one patients with mild maturity-onset diabetes were given introduodenal infusions of an amino acid mixture (0.5 g amino acids per kg body weight). In 9 other patients L-arginine was infused intravenously in a constant dose of 25 g. Alpha-amino nitrogen, blood glucose and plasma insulin levels were assayed under control conditions and after three days of treatment with phenformin, 150 mg daily, plus the same 150 mg dose 60 min before the second loading. Intraduodenal infusion of the amino acid mixture provoked a greater increase in plasma insulin than intravenous infusion of L-arginine, this increase being significantly inhibited by phenformin only in the first case. Since no evident influence of phenformin on the intestinal absorption of amino acids could be demonstrated, this effect may be explained by a local action on the intestinal wall exposed to high concentrations of the drug, resulting in the inhibition of the insulin secretion stimulating activity of the gut.