Estimated glomerular filtration rate, albuminuria and mortality in type 2 diabetes: the Casale Monferrato study.

AIMS/HYPOTHESIS: Estimated glomerular filtration rate (eGFR) predicts mortality in non-diabetic populations, but its role in people with type 2 diabetes is unknown. We assessed to what extent a reduction in eGFR in people with type 2 diabetes predicts 11-year all-cause and cardiovascular mortality, independently of AER and other cardiovascular risk factors. MATERIALS AND METHODS: The study population was the population-based cohort (n = 1,538; median age 68.9 years) of the Casale Monferrato Study. GFR was estimated by the abbreviated Modification of Diet in Renal Disease Study equation. RESULTS: At baseline, the prevalence of chronic kidney disease (eGFR <60 ml min(-1) 1.73 m(-2)) was 34.3% (95% CI 33.0-36.8). There were 670 deaths in 10,708 person-years of observation. Hazard ratios of 1.23 (95% CI 1.03-1.47) for all-cause mortality and 1.18 (95% CI 0.92-1.52) for cardiovascular mortality were observed after adjusting for cardiovascular risk factors and AER. When five levels of eGFR were analysed we found that most risk was conferred by eGFR 15-29 ml min(-1) 1.73 m(-2), whereas no increased risk was evident in people with eGFR values between 30 and 59 ml min(-1) 1.73 m(-2). In an analysis stratified by AER categories, a significant increasing trend in risk with decreasing eGFR was evident only in people with macroalbuminuria. CONCLUSIONS/INTERPRETATION: Our study suggests that in type 2 diabetes macroalbuminuria is the main predictor of mortality, independently of both eGFR and cardiovascular risk factors, whereas eGFR provides no further information in normoalbuminuric people.

Effect of age on the association of non-high-density-lipoprotein cholesterol and apolipoprotein B with cardiovascular mortality in a Mediterranean population with type 2 diabetes: the Casale Monferrato study.

AIMS/HYPOTHESIS: Measurement of plasma apolipoprotein (Apo) B may improve prediction of cardiovascular risk, as it provides a measure of the total number of atherogenic particles. The aim of this population-based study was to compare the association of non-HDL-cholesterol, ApoB and the ApoB:ApoA-I ratio with cardiovascular mortality in people with type 2 diabetes. SUBJECTS AND METHODS: We assessed the association of lipids, lipoprotein lipids and apolipoproteins with 11-year mortality from cardiovascular disease in the population-based cohort of the Casale Monferrato Study (1,565 people with diabetes; median age 68.9 years), and determined the effect of age (< or =70 and >70 years) on these relationships. RESULTS: On the basis of 341 deaths from cardiovascular disease in 10,809 person-years of observation, there was a decreasing trend in risk adjusted for multiple factors across quartiles of total cholesterol, and LDL- and non-HDL-cholesterol in people aged >70 years, but no trend in those aged < or =70 years. Age did not affect the protective effect of HDL-cholesterol. ApoB and ApoB:ApoA-I were associated with outcome in people in both age groups independently of non-HDL-cholesterol. After adjustment for multiple factors, including non-HDL-cholesterol, the hazard ratios for ApoB:ApoA-I in the upper vs lower quartile were 2.98 (95% CI 1.15-7.75; p for trend=0.009) for people aged < or =70 years and 1.94 (95% CI 1.20-3.13; p for trend=0.003) for those aged >70 years. CONCLUSIONS/INTERPRETATION: In this cohort of Mediterranean subjects with diabetes, ApoB and the ApoB:ApoA-I ratio were associated with cardiovascular disease mortality independently of non-HDL-cholesterol. Our findings support the recommendation that ApoB and ApoA-I should be measured routinely in all people with diabetes, particularly in the elderly.

Fibrinogen and AER are major independent predictors of 11-year cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study.

AIMS/HYPOTHESIS: Fibrinogen and elevated AER increase cardiovascular mortality, but few data are available in the type 2 diabetic population. We have conducted an 11-year follow-up study of the Casale Monferrato cohort to assess: (1) the long-term predictive role of AER independently of conventional risk factors; (2) the shape of its relationship with cardiovascular mortality; and (3) whether fibrinogen has a predictive effect independent of the increased cardiovascular risk associated with nephropathy. METHODS: During the follow-up period (1991-2001) a population-based cohort of 1,565 patients was regularly examined, and measurements of HbA1c were centralised. Multivariate Cox proportional hazards modelling was employed to assess the role of fibrinogen and AER as predictors of all-cause and cardiovascular mortality, independently of baseline variables and individual cumulative average values of HbA1c during follow-up. RESULTS: In 10,890.2 person-years of observations, 685 deaths were identified, giving an all-cause mortality rate of 63.4 per 1,000 person-years (95% CI 58.8-68.3). In Cox regression analyses, the strongest predictor of cardiovascular mortality was macroalbuminuria (relative risk 2.18, 95% CI 1.62-2.94), which was mainly associated with a high risk of short-term mortality. No increased risk was evident until the upper microalbuminuric range of AER values. Plasma fibrinogen was also a major independent predictor, and its role was not modified by AER, or by the exclusion of subjects developing chronic renal failure or diabetic nephropathy during follow-up. CONCLUSIONS/INTERPRETATION: The results indicate that: (1) AER is the main independent predictor of 11-year cardiovascular mortality; (2) this effect is mainly evident in the upper range of microalbuminuria and in macroalbuminuria; and (3) fibrinogen has an independent effect on cardiovascular mortality, but no synergistic effect with AER, suggesting that both endothelial dysfunction and chronic inflammation are involved in the excess cardiovascular mortality of type 2 diabetic patients.

Sex-differences in prevalence of electrocardiographic left ventricular hypertrophy in Type 2 diabetes: the Casale Monferrato Study.

UNLABELLED: AIMS Although left ventricular hypertrophy (LVH) defined by either standard 12-lead ECG or echocardiography strongly predicts cardiovascular mortality, its prevalence in Type 2 diabetes is largely unknown. We have assessed prevalence of ECG-LVH and its relationship with clinical and metabolic variables in an Italian population-based cohort of subjects with Type 2 diabetes. METHODS The study-base was 965 (61.3%) subjects with Type 2 diabetes of the population-based cohort living in Casale Monferrato (Italy). LVH was defined by ECG Cornell voltage-duration product. All measurements were centralized. RESULTS ECG-LVH was diagnosed in 165/965 subjects, giving a prevalence of 17.1% (95% CI 14.7-19.5). Large sex differences were found, with higher prevalence in women (23.5%, 19.9-27.0) than in men (8.4%, 5.6-11.0), even after adjustment for age, BMI and hypertension (OR 3.83, 95% CI 2.5-5.9). At the examination, subjects with ECG-LVH were older than those without it. Similar age- and sex-adjusted values of HbA(1c), plasma lipids, fibrinogen, uric acid and creatinine were found in the two subgroups. No differences in prevalence of hypertension, CHD, increased QT duration or dispersion, micro- and macro-albuminuria were found between subjects with ECG-LVH and those without it. In logistic regression analysis, variables independently associated with ECG-LVH, after age-adjustment, were sex and diastolic blood pressure. CONCLUSIONS: This population-based study shows: (i) a high prevalence of ECG-LVH in Type 2 diabetic subjects; (ii) 3-fold higher risk in women than in men, independently of age, BMI, and blood pressure; (iii) an independent association between ECG-LVH and diastolic blood-pressure. Screening for ECG-LVH in diabetic subjects is therefore recommended, particularly in diabetic women.

Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population-based cohort.

OBJECTIVE: To evaluate the prevalence of prolonged QT interval and dispersion in a population-based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables. DESIGN: Cross-sectional population-based cohort. SETTING: Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy). SUBJECTS: A total of 1357 patients with known type 2 diabetes (70% of the cohort). MAIN OUTCOMES MEASURES: Albumin excretion rate and coronary heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged. RESULTS: Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (beta=0.010, P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD was found (beta=0.20, P < 0.001, R2=4.8%). CONCLUSIONS: This population-based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.

Hyperfibrinogenemia and metabolic syndrome in type 2 diabetes: a population-based study.

BACKGROUND: It has been hypothesized that fibrinogen clusters with several components of the metabolic syndrome, thus increasing its cardiovascular risk. The aims of the present study were to assess in a large population-based cohort of patients with type 2 diabetes (1) variables associated with fibrinogen and (2) the relationship between hyperfibrinogenemia, a number of components of the metabolic syndrome, and coronary heart disease (CHD). METHODS: We identified a cross-sectional, population-based cohort of 1574 patients with type 2 diabetes using multiple sources of ascertainment. Components of the metabolic syndrome were hypertension (systolic blood pressure > or = 160 mmHg and/or diastolic blood pressure > or = 95 mmHg and/or treatment with antihypertensive drugs), dyslipidemia (tryglicerides >2.82 mmol/l and/or HDL-cholesterol <1.03 mmol/l), hyperuricemia (uric acid >416 micromol/l) and increased albumin excretion rate (AER > or = 20 microg/min). RESULTS: Fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, even after adjustment for confounders. Prevalence of CHD increases linearly across quartiles of fibrinogen (from 26.1 to 40.6%, p=0.046). However, in logistic regression, after adjustment for both confounders and known risk factors for CHD, the role of fibrinogen is no more significant, whereas ORs for HbA(1c) between 6.8 and 8.8% and >8.8% vs values <6.8% are, respectively, 1.91 (95% CI 1.36-2.69) and 1.56 (1.07-2.27). CONCLUSIONS: This population-based study shows that fibrinogen increases with age, HbA(1c), smoking, hypertension and a number of components of the metabolic syndrome, independent of major confounders. We also found that poor blood glucose control was associated with CHD.

Cardiovascular risk profile of type 2 diabetic patients cared for by general practitioners or at a diabetes clinic: a population-based study.

The aims of this study were to compare the cardiovascular risk profiles of patients with type 2 diabetes mellitus cared for by general practitioners and those regularly attending a diabetes center. Out of an Italian population-based cohort of 1967 diabetic patients, 1574 (80%) were investigated. Patients exclusively cared for by general practitioners (23.8%) were older and showed lower prevalence of hypertension (79.0% vs 85.9%, P < 0.001), poor blood glucose control (HbA1c >8.0, 33.4% vs 47.9%, P < 0.001) and coronary heart disease (18.1% vs 22.3%, P = 0.003), and lower plasma fibrinogen (3.5 +/- 0.8 vs 3.7 +/- 0.9 g/L, P < 0.001). In logistic regression analysis, they had significantly lower ORs for HbA1c >8.8% (OR 0.67, 95% CI 0.45-0.99), hypertension (OR 0.53, 95% CI 0.36-0.78), fibrinogen >4.1 g/L (OR 0.50, 95% CI 0.32-0.77), smoking (OR 0.60, 95% Cl 0.36-1.00), and coronary heart disease (OR 0.65, 95% CI 0.45-0.93), after adjustment for age, sex, duration of diabetes, BMI, and antidiabetic treatment. Patients regularly cared for at a diabetes clinic had a higher cardiovascular risk profile, suggesting selective referral to the clinics of patients with more difficult management and/or severity of the disease. These findings have implications in the interpretation of morbidity and mortality clinic-based studies.

Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of type II (non-insulin-dependent) diabetes mellitus.

The aims of this study were to assess the impact of diabetes and associated variables (fasting plasma glucose, blood pressure, antidiabetic treatment, body mass index) on general and cause-specific mortality in an Italian population-based cohort with Type II (non-insulin-dependent) diabetes mellitus, comprising mainly elderly patients. The patients (n = 1967) who had Type II diabetes were identified in 1988 with an 80% estimated completeness of ascertainment. In 1995, a mortality follow-up (98% completeness) of the cohort was done amounting to a total of 11153 person-years. Observed and expected number of deaths were 577 and 428.7, respectively, giving a standardized mortality ratio (SMR) of 1.35 (95% CI 1.24-1.46). The most common underlying causes of death were malignant neoplasm, ischaemic heart disease and cerebrovascular diseases, which accounted for 18%, 17.8% and 17.5% of deaths, respectively. Cardiovascular disease as a whole (international classification of disease ICD-9 390-459) accounted for 260 of 577 deaths (SMR 1.21, 95% CI 1.07-1.36). In internal analysis, the most important predictors of general mortality were insulin-treatment (relative risk [RR] 1.72, 95% CI 1.19-2.49) and a fasting plasma glucose greater than 8.89 mmol/l ([RR] 1.29, 95 % CI 1.04-1.60), whereas the most important predictors of cardiovascular diseases were insulin-treatment and hypertension. In conclusion, this population-based study showed: 1) slight mortality excess of 35% in Type II diabetes being associated with 2) a 30% increased mortality in subjects with baseline fasting glucose greater than 8.89 mmol/l and 3) a 40% increased risk of death from cardiovascular diseases in hypertensive patients.

Glycaemic control and cardiovascular risk factors in type 2 diabetes: a population-based study.

The objective of this study was to estimate the prevalence of poor glycaemic control and cardiovascular risk factors in an Italian population-based cohort of subjects with Type 2 diabetes mellitus (DM). Out of a cohort of 1967 subjects (estimated completeness of ascertainment 80%), 1574 (80%) were investigated, and adherence to targets for control of the European NIDDM Policy Group assessed. Prevalence of poor glycemic control (HbA1c > = 8) was 47.7%. Obesity was present in 23.4% of the cohort, hypertension in 83.4%, hypertriglyceridaemia (>2.26 mM) in 19.3%, hypercholesterolaemia (>6.46 mM) in 25.5%, and low HDL-cholesterol (<0.90 mM in men and <1.03 mM in women) in 13.7%. Only 153 (9.7%) subjects were free from other disorders. Subjects were treated as follows: 26.2% exclusively by general practitioners; 13.3%, 69.9%, 10.9%, and 5.9% with diet, oral hypoglycaemic drugs, insulin, and both, respectively. Multiple linear regression analysis showed associations between HbA1c and fibrinogen (p < 0.001), total cholesterol (p = 0.006), and triglycerides (p = 0.04), independent of age, sex, duration of diabetes, and antidiabetic treatment. Neither BMI nor blood pressure were associated with HbA1c. In conclusion, this Italian population-based cohort of subjects with Type 2 DM showed a high prevalence of poor glycaemic control, high consumption of oral hypoglycaemic drugs, and an independent association between glycaemic control and cardiovascular risk factors (fibrinogen, total cholesterol, and triglycerides). The presence of obesity or hypertension was not significantly associated with glycaemic control.

Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: The high prevalence of classic cardiac risk factors in patients with non-insulin-dependent diabetes mellitus does not explain the increased cardiovascular-related morbidity and mortality in these patients. Fibrinogen may have a role in this excess risk. OBJECTIVE: To evaluate the following in patients with non-insulin-dependent diabetes mellitus: 1) the distribution of plasma fibrinogen levels and the prevalence of hyperfibrinogenemia and 2) the association of fibrinogen level with hemoglobin A1c value and albumin excretion rate. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rural area in northern Italy. PATIENTS: 1574 patients with non-insulin-dependent diabetes mellitus who represented 81% of the initial cohort of 1967 patients. MEASUREMENTS: Albumin excretion rate was measured in urine samples obtained during an overnight collection. Venous blood samples were collected while patients fasted. RESULTS: Fibrinogen levels were available for 1525 of the 1574 patients who were examined (669 men and 856 women). The mean age (+/- SD) was 67.3 +/- 10.3 years for men and 70.7 +/- 10.7 years for women. The mean plasma fibrinogen level (+/- SD) was 3.6 +/- 0.9 g/L; levels slightly differed between men and women. In 50.3% of patients, plasma fibrinogen level exceeded 3.5 g/L. In men, fibrinogen level increased with age (P < 0.001). In both men and women, fibrinogen level adjusted for age and sex was significantly and linearly related to hemoglobin A1c value (P < 0.001) and albumin excretion rate (P < 0.001). In a multiple regression analysis, hemoglobin A1c value (b = 0.06; P < 0.001) and albumin excretion rate (b = 0.09; P = 0.005) were associated with fibrinogen level independent of other cardiovascular risk factors (sex, age, hypertensive status, total cholesterol level, smoking habit, and body mass index). CONCLUSIONS: Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.

Prevalence and risk factors for micro- and macroalbuminuria in an Italian population-based cohort of NIDDM subjects.

OBJECTIVE: To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS: Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS: The prevalences of microalbuminuria (AER 20-200 micrograms/min), macroalbuminuria (AER > 200 micrograms/min), and hypertension were 32.1% (95% CI 29.8-34.4), 17.6% (15.7-19.5), and 67% (64.6-69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04-1.66 for microalbuminuria and OR 1.63, 1.22-2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS: This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

Prevalence and clinical features of known type 2 diabetes in the elderly: a population-based study.

In a large population-based survey, 1947 Type 2 diabetic subjects aged 40 yr and over were identified, with high ascertainment (91%). Age-specific prevalence increased from 2.48% in the age group 40-64 to 5.62% in the age group > or = 65 yr; 35% of subjects were 65 yr and over at the onset of the disease. Elderly diabetic subjects showed a significantly (p < 0.001) lower frequency of family history of diabetes (26% vs 42%), obesity at diagnosis (62% vs 70.6%) and fasting plasma glucose (FPG) (8.3 +/- 2.4 vs 8.1 +/- 2.8 mmol l-1). Elderly diabetic subjects were more commonly managed by general practitioners (GPs) (29.7% vs 21.5%). Elderly patients attending only the GPs differed in FPG, which was significantly lower (7.9 +/- 2.1 nmol l-1 vs 8.5 +/- 2.6 mmol l-1). Good metabolic control (FPG < 6.6 mmol l-1) was found in 17.5% of subjects in the age group 40-64 and in 22.9% in the age group > or = 65 yr. Poor metabolic control was more commonly seen in those attending the diabetic clinic. HBA1c measurement was available in 32.0% of the elderly attending the diabetic clinic and in only 10.7% of those in the care of GPs. Fundal examination was available in 48.2% and in 36.5%, respectively, of diabetic subjects in the age groups 40-64 > or = 65 yr, without differences between those attending and those not attending the diabetic clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

A population-based prevalence survey of known diabetes mellitus in northern Italy based upon multiple independent sources of ascertainment.

The aims of this survey were (1) to estimate the prevalence of known diabetes mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different data sources available in Italy; (3) to identify a population-based cohort of diabetic patients. Multiple independent data sources were used and the capture-recapture method was applied to estimate the completeness of ascertainment of the survey. The primary data source was the list of all patients attending the diabetic clinic or those referred by family physicians and paediatricians of the area. The secondary data sources were the list of hospital discharges, the prescriptions data source and the list of all people using reagent strips and insulin syringes. On 1 October 1988 (the cut-off date) 2,069 cases of known diabetes were identified. The estimated completeness of ascertainment of the survey was 91%. Prevalence of known diabetes, Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) and insulin-treated diabetes were, respectively, 2.21% (95% CI 2.13-2.29), 0.80/1,000 (0.62-0.98) and 2.10% (2.01-2.19), 2.92/1,000 (2.57-3.27). A higher prevalence of Type 2 diabetes was observed in women (2.30%, 2.18-2.42) than in men (1.88%, 1.76-2.00). Age-specific prevalence of Type 2 diabetes increased with age. Computerized data sources routinely available in the Piedmont Region (hospital discharges and prescriptions data sources) showed a low completeness of ascertainment when considered together (65%, 1,338 of 2,069), indicating the need to involve the diabetic clinic and family physicians in the ascertainment of known diabetes. In conclusion, the prevalence of known diabetes in Italy was lower than in Northern Europe and the United States.

[Treatment of diabetes mellitus with an artificial pancreas]. / Trattamento del diabete mellito con il pancreas artificiale.

The results obtained with an artificial pancreas in 34 diabetics (15 women, 19 men) are reported. The group included 20 insulin dependent and 14 non-insulin dependent cases and the applicability of the technique is discussed.

[Diabetes and surgical interventions]. / Diabete e interventi chirurgici.

Due to the ways their disease develops diabetics are more likely to require surgery than the rest of the population and operations constitute a stress factor with high rates of morbidity and post-operative mortality due essentially to cardiovascular and infectious complications. In normal subjects the stimulation of the hypothalamohypophyseal axis and the suprarenal marrow induced by surgical stress mobilizes energy substrates that provoke the secretion of insulin that prevents their accumulation and improves their utilization. In diabetics the inadequacy or lack of insulin secretion unbalances these mechanisms to the great danger of the patients themselves. For this reason patients' pre-operative conditions must be very carefully assessed and treatment designed to prevent the increase of catabolic ways due to the lack of insulin must be given. Some of the many treatment protocols proposed are described and discussed, a distinction being made between diet, non insulin and insulin dependent diabetics. The post-operative risk constituted by the onset of non-ketoacidotic hyperosmolar coma, as occurs in other severe stress situations should also be remembered.

[Relations between the site of insulin absorption and hypoglycemia in insulin-dependent diabetes during physical exertion]. / Rapporto tra sedi di assorbimento dell'insulina e ipoglicemia nel diabete insulino-dipendente durante l'esercizio fisico.

Hypoglycaemia often arises after physical exercise in insulin-dependent diabetics treated with fast and slow acting insulin. Some claim that this is closely linked to the injection site for fast insulin and related to altered mobilization of the hormone from its subcutaneous deposit. Others attribute it to hyperinsulinism. The hypoglycaemia occurring after physical exercise in subjects treated with slow insulin and that arising even hours after physical exercise are then considered.

[Oral contraceptives and diabetes]. / Contraccettivi orali e diabete.

Some remarks are presented on the contraceptive treatment of diabetic females with emphasis on the relationship between progestins and estrogenic progestins and the metabolism of carbohydrates and fats, haemostasis and arterial hypertension. Indications for the contraceptive treatment of insulin dependent and non-insulin dependent diabetics and subjects exposed to diabetic risk are supplied.

[Diabetes and autoimmune diseases. I]. / Diabete e malattie autoimmuni. Parte I.

An account is given of the clinical and serological associations between diabetes and autoimmune diseases, especially those between diabetes and antihyperoglobulin, antithyroid, anti-intrinsic factor, anticorticoadrenal cell, and anti-nucleic acid autoantibodies. Body fluid antipancreas autoimmunity is examined from various standpoints relating to antipancrease cell antibodies (ICA), autoantibodies against glucagon-secreting cells (ECA) and somatostatin-secreting cells (SCA), and anti-islet cell surface antibodies (McLaren and Lernmark antibodies). Particular attention is directed to ICAs, since these have supplied the background for the recent division of type I diabetes into Ia viral and Ib autoimmune. Stress is laid on both the soundness and the problems forming part of ICAs, since their actual pathogenetic role (cytoplasmic markers?) still has to be determined, even though their persistent and significant association with autoimmune polyendocrinopathies is certain.

[Diabetes and autoimmune diseases. II]. / Diabete e malattie autoimmuni. Parte II.

Antipancreas autoimmunity is one of several immunity problems in diabetes. Such of its features as are revealed by inhibition of leukocyte migration, lymphocyte transformation in response to insulin antigens, relation between cell autoimmunity and later complications, and the behaviour of peripheral T and B lymphocyte membrane markers are explained. The aetiological role of viral infections is discussed, and the pathogenetic hypothesis deducible from the histological findings. Lastly, the modalities underlying a combination between the HLA (human leukocyte antigen) system and diabetes are considered.

[Clinical observations on the treatment of ischemic cardiac disease with a calcium antagonist: nifedipine]. / Osservazioni cliniche sul trattamento della cardiopatia ischemica con un calcio-antagonista: la Nifedipina.

Results obtained wih Nifedipine in 146 coronary patients, 85 of them suffering from coronaro-sclerosis with rest and effort stenocardic attacks, and 61 with post-infarctual stenocardic signs, are reported. In 76% of patients in the first group and in 85% of those in the second, pain symptomatology disappeared rapidly; ECGs also showed attenuation and modification, particularly among angina patients. The drug also led to a reduction in hypertension.