[Lactic acidosis and severe hyperkalemia in a diabetic patient treated with metformin and enalapril: influence of acute renal disease and drugs]. / Acidosi lattica ed iperpotassiemia grave in un paziente diabetico in terapia con metformina ed enalapril: influenza di patologia renale acuta e farmaci.

A 71 year old hypertensive and non insulin-dependent diabetic patients with moderate renal insufficiency taking 500 mg/d of metformin and 5 mg/d of enalapril, developed metabolic acidosis characterized by fairly elevated anion gap, hyperchloremia, severe hyperkalemia, normal plasma level of beta-hydroxybutyric acid, absence of ketonuria and high plasma level of lactic acid. This biochemical feature allowed us to ascribe the pathogenesis of metabolic acidosis both to the increased plasma level of lactic acid and to the type IV renal tubular acidosis syndrome, the precipitating factor being an infection of urinary tract (as we assumed on the basis of the urine culture). The patient was dehydrated and lethargic; the ECG revealed the presence of nonparoxysmal junctional tachycardia. The clinical evolution was favorable thanks to the treatment with the infusion of isotonic saline solutions, mild alkalinizing solutions, low-dose regular insulin and antibiotics. It is likely that metformin and enalapril, regularly assumed by the patient, could have played a iatrogenic role even if they were taken in low dosages. This event points out the importance of complying with the indications and especially the contraindications of these drugs, to avoid life threatening complications as that one occurred in this case.

[Major histocompatibility complex antigens in a population of insulin-dependent diabetics living in the Province of Varese]. / Gli antigeni del sistema maggiore di istocompatibilità in una popolazione di soggetti diabetici insulinodipendenti residenti in Provincia di Varese.

The HLA haplotype was studied in 143 newly diagnosed insulin-dependent diabetic subjects resident in the province of Varese who attended the clinic between March 1987 and June 1993. The frequency with which the various loci of the histocompatibility system were observed was compared with that reported in 83 non-diabetic subjects not related to the diabetics taking part in the study. The relative risk (RR) was calculated using these data and its statistical significance was assessed using the chi-square test. 70.6% of subjects were positive for loci DR3 or DR4, whereas only 7.7% (11 subjects) were found to be carriers of eterozygous DR3-DR4. This percentage is lower than that generally reported in the literature. However, even in the authors personal experience heterozygous DR3-DR4 subjects represent the greatest relative risk in absolute terms (RR = 14.49). The presence of antigen DQw2 is strongly indicative of the disease, both when it is found in an isolated form and in association with DR3 or DR4 (RR = 2.56, 4.03, 3.29 respectively). The DR3/DR4/DQw2 axis gives a RR of 9.17. The associations of B8/DR3/DR4 and B8/DR3/DQw2 give a RR of 9.17, whereas the B8/DR4 axis gives a RR of 10.47. In this series, the lowest risk of developing the disease was provided by the DR2/DR7 axis (RR 0.28); DR2 alone gave a RR of 1.84 and DR7 alone gave a RR of 0.62. The discrepancies reported with the literature may be related to ethnic variations, thus giving added weight to the hypothesis of the heterogeneity of insulin-dependent diabetes mellitus.

Serum lipid pattern as severity indicator of angiographically assessed coronary artery disease.

In this study we compared the relative utility of plasma lipid and apolipoprotein pattern as predictor of extent of Coronary Artery Disease as angiographically established. The lipid and apolipoprotein values were plotted in multiple stepwise analysis against coronary score determined as follows: at least 1 coronary artery system (left, anterior, descendent, circumflex, right) with a >/= 25% stenosis 1 point, number of involved vessel 1, 2, 3, .... adjunctive points; sequential lesions +1 point; < = %50% stenosis +1 point; 75-95 % +2 points; > 95% +3 points. The statistical analysis demonstrate a strong influence on extent of disease by total-cholesterol, % HDL-cholesterol on total cholesterol and by the difference between LDL and HDL-cholesterol. We conclude that, in predicting the extension of CAD, is important to know how total cholesterol is distributed in plasma apolipoprotein system.

"Cardiovascular risk factors in insulin dependent diabetes".

Diabetics have an increased risk of cardiovascular morbidity and mortality. Compelling evidence suggests that there is cause-effect relationship between alterations of serum lipids and lipoproteins, and atherosclerosis and coronary heart disease in non diabetic-population. Among insulin dependent diabetics, the prevalence of macrovascular disease is particularly increased in those with established clinical nephropathy and it has been partly attributed to concomitant hypertension and serum lipoprotein abnormalities. However, the effect of diabetic nephropathy and factors associated with it on Coronary Artery Disease (CAD) appears to be conditional. Many Patients in many studies did not have CAD despite a long duration of persistent proteinuria and renal failure There is the possibility that CAD is an outcome of a multistage process, and diabetes related conditions may accelerate progression through certain stage only. In that case, the pattern of appearance of CAD would be determined by the natural history of atherosclerosis rather than by duration of diabetes. The purpose of our study is to analyze retrospectively the incidence of CAD and its association with blood pressure, serum total cholesterol, HDL cholesterol, duration of diabetes, serum triglycerides and HbAlc in a cohort of insulin dependent diabetic patients without nephropathy.

[Metabolism of the ischemic myocardium in non-insulin-dependent diabetes]. / Il metabolismo del miocardio ischemico nel diabete non insulinodipendente.

Fourteen non-insulin-dependent diabetics enjoying good metabolic balance with diet alone and who had presented typical effort-induced angina symptomatology for at least two years have been examined. They were subjected to atrial pacing in accordance with routine protocols and blood samples were taken from the aortic bulb and from the coronary sinus for the measurement of glucose, triglycerides, NEFA, lactate, pyruvate and glycerol. The results obtained show an ischaemic type metabolism even under basal conditions, accentuated after effort. The reduction in triglycerides in the coronary sinus is only apparent and, through the mechanism of the increased production of NEFA, may account for the increase in mortality from acute myocardial infarction in the non-insulin-dependent diabetic.

[Action of evening primrose oil on cardiovascular risk factors in insulin-dependent diabetics]. / L'azione dell'olio di "evening primrose" sui fattori di rischio cardiovascolare dei diabetici insulino-dipendenti.

In an open study, the authors compared two groups of insulin-dependent diabetics matched for age and metabolic control, one of which was given a linoleic-gamma-linolenic acid mixture (3 g daily), the other served as control. The effect, attributed to gamma-linolenic acid only, was evaluated as explained in the text and is shown in the table. At the end of two months no change was found in the control group while favorable changes of HDL-cholesterol and platelet adhesiveness were observed in the experimental group.

[Correlation between the metabolic follow-up and diabetic retinopathy]. / Correlazione tra stato di controllo metabolico e retinopatia diabetica.

The state of the fundus oculi was investigated in 40 insulin-dependent and 20 non-insulin dependent diabetics. In both groups the state of the fundus oculi was correlated with total cholesterol, LDL, HDL, glycosylated haemoglobin, platelet adhesiveness, triglycerides and duration of the disease. In the case of insulin-dependent diabetics a correlation was also sought with daily doses of insulin. The fundus oculi was normal in 21/40 insulin-dependent and 14/20 non-insulin-dependent subjects. Multiple regression showed a positive correlation between insulin-HbA doses and duration of the disease and the fundus oculi. Simple liner regression showed a negative correlation between insulin doses and fundus, a tendentially positive correlation between platelet adhesion and fundus. A positive correlation between LDL-platelet adhesion and fundus was also shown in the non-insulin-dependent subjects. These results suggest that factors held to influence macroangiopathy also have an effect on macroangiopathy, that the check up of diabetics is important for the prevention of retinopathy, that insulin doses should be strictly limited to the necessary amount for the control of diabetes since excess is as harmful as insufficiency.

[Our experience with biosynthetic human insulin]. / La nostra esperienza con insulina umana biosintetica.

Biosynthetic Human Insulin (BHI) was administered to 20 diabetics for six months. A clinical examination, glycaemia before and after eating, total glycosuria-ketonuria, and glycosylated haemoglobin tests were performed at fixed intervals, and the results were statistically analysed. It is concluded that human insulin produces no significant side effects. More important that the type of insulin treatment is effective outpatients surveillance of the diabetic, to ensure an adequate metabolic compensation.

[Blood glucose regulation in Bartter's syndrome. Observations in 2 cases]. / La regolazione glicemica nella sindrome di Bartter. Osservazioni su due casi.

Two cases (two sisters) of Bartter's syndrome are reported in which evident disturbance of the glycaemia regulation system was observed alongside other elements typical of the syndrome. The data are discussed in the light of recent aetiopathogenetic hypotheses about Bartter's syndrome. It is concluded that the physiopathological condition is also directly responsible for the disturbance in glycoregulation.

Possible glucagon-mediated hypocholesterolemic activity of a nicotinic acid derivative (sorbinicate).

The antilipolytic activity of nicotinic acid was investigated in 7 patients with type II b hyperlipoproteinemia and in 7 with type IV hyperlipoproteinemia treated for two months with a nicotinic acid derivative, sorbinicate (1600 mg daily, ie 1454 mg NA). Before and after treatment the blood levels of total cholesterol and triglycerides were determined and three dynamic tests -- oral glucose tolerance test, insulin test and tolbutamide test -- were done to check in each test the variations in blood glucose, NEFA, insulin (excluding obviously the insulin test), glucagon and growth hormone levels. At the end of the treatment, there was a significant reduction of cholesterol (type IIb and type IV) and of triglycerides (type IV), a marked reduction of the glucagon response, a slight increase in the insulin response and in the basal secretion of the growth hormone. It is suggested that the antilipolytic activity of nicotinic acid (and hence of sorbinicate) is at least partly mediated by an inhibition of glucagon secretion (and/or synthesis).

[Leukemic reticuloendotheliosis. Problems in differential diagnosis apropos of our study of 1 case]. / La reticoloendoteliosi leucemica. Problemi di diagnosi differenziale a proposito di una nostra osservazione

A case of leukaemic reticuloendotheliosis is reported. The clinical and histocytological picture of the disease is discussed in relation to the complex problems of differential diagnosis it involves with other forms of systemic involvement of the spleen. The electivity of splenectomy is stressed.