Insulin-dependent diabetes mellitus in Sardinian-heritage children living in Lombardy.
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Biomedical subjects
Publications and source records attributed to G Gallus.
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OBJECTIVE: To evaluate, under routine conditions, the relation between different diabetes care policies and glycemic control through a by-center analysis procedure aimed at reducing some drawbacks of cross-sectional data. RESEARCH DESIGN AND METHODS: A survey on insulin-treated diabetes care management (IDDM and NIDDM) involved 16 Italian randomly selected diabetes outpatient clinics. A total of 2,142 representative patients were investigated. The standardized HbA1c average value of each center was related, by regression models, to some indicators of center care policy (average number of injections, average BMI, proportion of cases with recent fundus oculi examinations, or frequent visits) as well as to patients' average social levels (employment type). Homogeneity in patient admission criteria is assumed among the investigated centers as a basic condition for the procedure validity. Some known imbalance were controlled for both design and analysis. RESULTS: HbA1c showed a univariate inverse relation with daily number of injections in IDDM (P = 0.0009, r2 = 0.56) but not in NIDDM (P = 0.33). It was inversely related to both fundus examination (IDDM P = 0.04; NIDDM P = 0.099) and qualified employment (IDDM P = 0.06; NIDDM P = 0.026). A stepwise regression analysis left in the model insulin injections (P = 0.0002) in IDDM (total r2 = 0.68) and qualified employment (P = 0.016) and fundus examination (P = 0.14) in NIDDM (total r2 = 0.53), after controlling for age, sex, disease duration, insulin therapy starting delay, and insulin dose per kilogram. CONCLUSIONS: These results suggest that the confirmed benefits of a multiple-injection regimen in IDDM cannot be simply extrapolated to NIDDM, where patients' awareness and medical attention to complications proved to be the most important factors in current practice.
An overview of the placebo-comparative articles retrieved by a literature search on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME). Ten original published studies were reviewed by an independent physician who assessed their quality by standard nine-items methodology. A meta-analytical approach was used to compare outcomes across all qualifying studies. Because of the heterogeneity of clinical endpoints, a new outcome measure was defined, i.e. overall clinical improvement, which consisted of the number of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. The objective evaluation criteria of normalisation of tympanogram was an additional end-point. Potential confounding variables such as eligibility criteria, treatment protocol and study design of the six methodologically complying studies were statistically homogeneous. No association was found between treatment effect-size and publication date or patients' age. Outpatients with disease duration of < 6 months, not previously treated, with bilateral ear involvement were included in the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were evaluable. Results from this meta-analysis indicate that patients with OME receiving oral SCMC/-lys benefit from the medical treatment to the extent of avoiding surgical intervention approximately 2.31 times more often than similar patients receiving placebo (ratio of active drug to placebo-effect on overall clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to normal of the tympanogram at an extent close to statistical significance (odds ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new methodology for the evaluation of the mucoactive drug effect in OME has shed light into methodological pitfalls of clinical trials to date and underlines the need for agreed outcome measures, which may modify medical policy, which addresses more and more often to symptomatic treatment.
PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.
OBJECTIVE: To estimate the overall and age-specific incidence of known diabetes and its total duration through prevalence data and to assess the consistency of the results by mortality analysis of the same cohort. RESEARCH DESIGN AND METHODS: Two different sources were used. The first was a representative sample of 2,274 prevalent known-diabetic subjects. These data provided overall and age-specific incidence estimates by fitting a logistic model to the partial incidence rates for different diagnosis cohorts and to the disease duration. The age at diagnosis structure was built from the age-specific estimates. Prevalence data also provided total duration estimates by converting the prevalent duration-to-date structure into an incident total duration structure. The second source was 145 deceased subjects who were taken from the 6-year follow-up sample of 1,132 prevalent subjects. The age at diagnosis and estimates of total disease duration were provided for these subjects, who paralleled the characteristics of the incident cohort. RESULTS: The two independent estimates of total disease duration were similar (prevalent subjects, 15.7 years; deceased subjects, 14.1 years): the average duration was 14.9 years. The ratio between prevalence and total duration yielded an independent yearly incidence estimate of 2.2 per 1,000 person-years (men, 2.0; women, 2.4), which was close to the value given by the model of 2.1 per 1,000 person-years (men, 1.9; women, 2.3). Also, the independently determined age structures overlapped, and their average was used to calculate the age-specific incidence. Incidence was negligible for individuals < 30 years of age, and it was about 6.0 per 1,000 person-years for individuals > 50 years of age. CONCLUSIONS: This study provided reliable estimates of NIDDM age-specific incidence rates and total disease duration, data that are seldom investigated in this type of disease.
PURPOSE: We evaluated the effectiveness of local bladder hyperthermia and intravesical chemotherapy compared to intravesical chemotherapy alone in the treatment of superficial transitional cell carcinoma. MATERIALS AND METHODS: A new system designed to deliver simultaneously local bladder hyperthermia and intravesical chemotherapy has been developed at our institute. The system consists of a computerized 915 MHz. microwave source that directly heats the bladder walls (within a temperature range of 42.5 to 45.5C) using a transurethral catheter. From February 1989 to December 1993, 52 patients 44 to 81 years old (mean age 64.3) with superficial stages Ta to T1, grades 1 to 3 transitional cell carcinoma of the bladder were selected for neoadjuvant intracavitary treatment. Tumors were left intact as marker lesions. Of the patients 29 were randomly assigned to receive combined neoadjuvant intravesical chemotherapy and local hyperthermia (group 1), while 23 received intravesical chemotherapy alone (group 2). The treatment protocol included multiple sessions performed on an outpatient basis. Mitomycin C (40 mg. in 50 cc distilled water) was used for intravesical chemotherapy in both groups. All patients underwent transurethral resection of residual tumors and of all suspicious areas 7 to 10 days after completion of treatment. Only a complete response was considered for statistical analysis. RESULTS: A pathological complete response was documented in 19 cases (66%) in group 1 and 5 (22%) in group 2 (chi-square p< 0.01). CONCLUSIONS: According to these preliminary data, microwave induced hyperthermia combined with local intravesical chemotherapy seems to be a feasible, safe and promising approach for neoadjuvant and minimally invasive treatment of superficial bladder cancer.
The association of cigarette smoking with the development of occlusive vascular disease is firmly established. Unfavourable changes in a series of variables held independent risk factors for the development of vascular lesions (HDL-cholesterol, haematocrit, white blood cell count, fibrinogen and plasminogen activator inhibitor-1 (PAI-1)) are thought to be directly influenced by cigarette smoking. However, the role played by the genotype in the effect of smoking on the above parameters has not been investigated. To control the genotype, we studied the relationship between cigarette smoking and a series of cardiovascular risk factors in 27 monozygotic twin pairs (7 male and 20 female pairs, mean age +/- SD: 47.4 +/- 12.9 yrs) with a life-long discordance for smoking. Smoking twins had a life-long dose of smoking (Brickman index) of 287.3 +/- 241.5. Body mass index, blood pressure, haematocrit, haemoglobin and red blood cell counts, total cholesterol levels and the acute phase reactants alpha 1-acid glycoprotein and C-reactive protein were similar in smokers and non-smokers. Triglyceride was higher by 12.6% (9.5-35%, 95% confidence interval, p = 0.02) and HDL-cholesterol lower by 7.5% (0.2-15%, p = 0.04) in the smoking co-twins, who also had 8.4% (-0.2-17%, p = 0.06) higher white blood cell counts and 4.1% (1.2-7%, p < 0.01) larger mean platelet volume. There was no significant difference in clottable fibrinogen (by two methods) or in the activity of plasminogen activator inhibitor-1 between the two groups, nor was the within-pair difference in these parameters related to the smoking dose. Echo-doppler examination of the carotid arteries of 24 twin pairs showed mostly minor atherosclerotic lesions in 46% and 42% of the smoking and non-smoking co-twins. After adjustment for age, systolic blood pressure and platelet count and volume were the only variables significantly associated to the presence of vascular lesions. Cigarette smoking is associated with an atherogenic lipid profile and with changes in platelets and white cells potentially reflecting endothelial cell damage. When controlling the genotype, fibrinogen and PAI-1 activity levels did not seem directly influenced by cigarette smoking.
To provide complete prevalence data on diabetes mellitus in Italy (diagnosed and undiagnosed), a population survey was performed in the Health District of Cremona, a representative area of the Po river (north Italy). The survey is characterised by particular attention being paid to methodology, non-responders being investigated for possible selection biases affecting diagnosed and undiagnosed diabetes prevalence estimations. Out of a population aged 44 years or older from three municipalities, a random sample of 3097 subjects was selected to undergo an oral glucose tolerance test. In addition, past medical history, clinical and laboratory data were collected. A total of 1797 subjects participated (58%), and information on known diabetes status was obtained for 2618 persons (85%), also including 826 interviewed non-participating subjects. Overall rates were age-standardised according to the 1991 Italian census. Overall prevalence and 95% confidence interval of diagnosed diabetes was 8.5% (6.9-10.1) in males and 7.9% (6.7-9.3) in females over the age of 44 years; previously undiagnosed diabetes was 2.5% (1.4-3.6) in males and 3.4% (2.1-4.7) in females; glucose intolerance was 7.7% (5.7-9-7) in males and 8.9% (7.0-10.8) in females. Total diabetes prevalence above age 44 years, developed-world age, and sex standardised, was 10.7%. This study provides the first reliable prevalence estimation of impaired glucose tolerance, diagnosed and undiagnosed diabetes in Italy, according to World Health Organization criteria, and one of the few figures for Southern Europe. The role of body mass index on both prevalence of diabetes and cluster of cardiovascular risk factors is considered, with implications for prevention.
Diabetes epidemiology can benefit in Italy from the large network of outpatient diabetic clinics and patients' facilities. A large investigation was carried out in 1988, in a certain area of northern Italy, to estimate the prevalence of known diabetes. Using four information sources, 4547 distinct patients were identified. Through the capture-recapture method we assessed completeness and estimated a prevalence of 3.3%. Prevalence of type 1 diabetes was 0.8 per 1000. Italian age-standardised overall prevalence and developed-world standardised rates were 2.8% and 2.6%, respectively. A representative sample of 2358 patients was characterised through a standard questionnaire. Women were diagnosed about 6 years later than men (58.8 +/- 0.4 vs 52.9 +/- 0.4, P < 0.0001), while the duration of the disease was very similar in both sexes (9.9 +/- 0.2 vs 9.5 +/- 0.2). As regards diabetes therapy, 17.2% of the patients were on diet alone, 62.1% on oral agents and 20.6% on insulin. Among the insulin-treated subjects more than half were on adjuvant therapy with tablets, and only 6.2% were treated with 3 injections/day. Less than half of all the known diabetic subjects had had an ophthalmoscopic examination in the previous 2 years.
Snoring is a prerequisite for obstructive sleep apnoea (OSA) and is known to run in families. Recent studies have provided sufficient evidence for a familial predisposition to OSA. In our study, 492 monozygotic and 284 dizygotic twins were contacted by telephone and asked to attend an interview which included questions of life habits, medical history, sleep habits and disorders, with particular emphasis on snoring. Our study showed that the probandwise concordance rate for habitual snoring was higher in monozygotic twins than in dizygotic ones, but the difference was not significant. The comparison of concordant pairs for habitual snoring vs. concordant pairs for non-snoring confirmed that habitual snoring is significantly associated with older age, male gender, higher body mass index (BMI), smoking and respiratory diseases. The multivariate analysis in the discordant groups confirmed that BMI is more strongly associated to habitual snoring in dizygotic twins than in the monozygotic ones. Our logistic analysis showed that other variables, such as smoking and respiratory diseases, are associated with habitual snoring in dizygotic pairs, but not in monozygotic ones. These findings suggest a genetic predisposition to habitual snoring.
A cross-sectional study of 2650 male and 751 female employees of the IBM company in the Milan area was conducted in 1987 to compare risk profiles for coronary heart disease between men and women and to analyse the awareness of risk status of people at risk. After age adjustment, the rate of cigarette smoking was higher in women (35%) than in men (25%). Other coronary heart disease risk factors were more common in men than in women. After controlling for age, 38% of the men and 19% of the women met the study criteria for hypertension, and 22% of the men and 17% of the women had high blood cholesterol. However, an analysis by age groups showed that, although in the younger age groups women had lower levels of cardiovascular risk factors, except smoking, compared to men, in the age brackets 50 or older women had similar or more adverse risk factor profiles than men. Of the people with hypertension, only 22% of the men and 19% of the women were aware of their hypertension, and only 2% of the men and 4% of the women had successful control by drugs. Even when subjects with mild hypertension were excluded, high proportions of undiagnosed and uncontrolled hypertension were found in both sexes. Of the individuals with serum cholesterol > or = 240 mg.dl-1, less than half of the men and less than 20% of the women were aware of their high blood cholesterol levels. Multiple risk factors were frequently present in the same individuals, especially among males and older women.(ABSTRACT TRUNCATED AT 250 WORDS)
For some time hyperthermia, alone or in combination with radiotherapy or chemotherapy, has proved to be a promising method for treating several kinds of solid tumors. After intensive laboratory investigations a new device, based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinically tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder. The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity. Endoscopic and histological evaluations proved that combined local hyperthermia and chemotherapy can induce necrosis of transitional tumors. The overall response rate was 90.8%, with 70.4% complete and 20.4% partial, leaving 4 patients (9.2%) nonrespondent. Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment. Further multicentric studies have been initiated.
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The aim of the present study, which is part of a larger population survey, is to provide an Italian estimate of the total prevalence of diabetes taking into account the fraction of known diabetes among the non-responders. The study consists of a population survey. Out of the population aged over 40 ys. of two municipalities, Casalbuttano and Vescovato, in the Health District of Cremona, a random sample of 2,229 subjects was selected to undergo an OGTT. In addition, a series of anamnestic, clinical, and laboratory data were collected for each individual. Overall response rate was 63%. Prevalence of known diabetes was 7.8% (6.5%-9.1%, 95% CI), (F = 7.9%, M = 7.6%). The comparison between responders and the telephone-interviewed non-responders showed an unpredictable and age- and sex-dependently varying frequency of known diabetes, even if the overall differences were not statistically significant. This suggests that, to avoid biases, many efforts should be spent to collect information about diabetes also for non-responders. Prevalence of unknown diabetes was 3.2% (2.2%-4.2%, 95% CI), (F = 4.0%, M = 1.8%) and total diabetes was 10.9% (9.3%-12.5%, 95% CI) (F = 11.9%, M = 9.4%). In contrast to other countries, the relationship between unknown and known diabetes was less than 1 to 2, and the proportion of unknown diabetes was almost negligible below the age of 70. A positive family history and a lower level of triglycerides were associated with awareness of the disease (p = 0.0005 and p = 0.006, respectively), thus suggesting different behaviour towards one's own health between known and unknown diabetic subjects.
BACKGROUND: This study was aimed at evaluating several factors that promote chronic hepatic encephalopathy by multivariate analysis of data for patients with cirrhosis with good or moderate liver function submitted to distal splenorenal shunts. METHODS: The study group comprised 131 patients: 55 had alcoholic and 76 nonalcoholic cirrhosis. Seventy patients were in Child's class A and 61 in class B. Cerebral function was assessed by a complete neurologic examination. Angiography with venous phase was performed before and within 1 month after the shunt operation. In 84 cases the original Warren technique was used and in 20 cases a Britton's modified procedure was used. Twenty-seven patients had distal splenorenal shunts with a splenopancreatic disconnection. Statistical analysis was performed by two multivariate analyses based on stepwise selection. RESULTS: Thirty-nine patients died during a follow-up period of 51 +/- 32 months. Chronic encephalopathy occurred in 18 patients (14%). According to the multivariate analysis of the preoperative prognostic factors, only age (p = 0.0001) and albumin values (p = 0.0002) were independent predictive risk factors for chronic encephalopathy. In the multivariate analysis concerning the hemodynamic consequences of the selective shunts, independent risk factors promoting chronic encephalopathy were postoperative portal perfusion (p = 0.0001), postshunt portal pressure (p = 0.001), and surgical disconnection (p = 0.0064). CONCLUSIONS: Our study has shown that chronic encephalopathy after selective shunt surgery is promoted by both clinical and hemodynamic factors. A better selection of the candidates for shunt surgery and prevention of the development of portal malcirculation by accurate surgical disconnection should further decrease the risk of chronic encephalopathy.
This study was undertaken to identify and validate possible existing sources of information to estimate the prevalence of known diabetes and the incidence of Type 1 (insulin-dependent) diabetes in Italy. The prevalence of known diabetes was estimated on the basis of data on drug sale, using specific defined daily doses as index of drug consumption. The estimation of the average daily dose used for calculations was carried out on a consecutive series of 911 diabetic subjects from two outpatient clinics. The incidence of Type 1 (insulin-dependent) diabetes was obtained by processing data routinely collected by the Regional Health Services, related to hospital discharge diagnosis records mentioning diabetes mellitus. The validation was carried out in 12 hospitals of the same Region. The estimated prevalence rate of known diabetes was 1.7%, including patients on dietary treatment. In the Lombardia Region in 1982-83 the estimated annual average incidence of Type 1 (insulin-dependent) diabetes, under the age of 35 was 4.6/100,000. This rate appears much lower then that observed in Northern Europe and the United States while it is similar to the French rate. This is in agreement with the findings of studies showing changes with latitude of the incidence rates of Type 1 (insulin-dependent) diabetes.
The Poisson approximation to a negative binomial process is evaluated regarding the surveillance of rare health events in the framework of the "Sets" scheme. This scheme defines an alarm in terms of "distance" between consecutive events of interest. The system's parameters are determined by minimizing the expected delay for an alarm when a given increase in the event rate has occurred, subject to a restriction on the rate of false alarms. It is shown that the main consequence of the Poisson approximation lies in an increase of the false alarm probability with respect to the assigned one, whilst influence on the expected delay for a true alarm is lower. It is, however, found that over a large range of practical instances, the Poisson assumption provides a reasonable description of the negative binomial process.
An incidence register for Type 1 diabetes was started in Lombardy in 1983-84 for people under 35 years of age. The main information source was the Regional Health Service record system, which provides anonymous reports on all patients discharged from public and private hospitals. Great care was taken to assure the quality of the data in the register. The clinical diagnosis was validated by examining the case notes. Completeness of the register was assessed using multiple independent sources of case ascertainment such as the list of the Youth Diabetics Association, the files of three hospital endocrinology centres, and the registry of conscripts rejected because of diabetes. The estimated age-adjusted (world standard) annual incidence rate was 6.04 per 100,000 in the group 0-18 years and 5.96 per 100,000 in the age group 0-14 years. Females had peak incidence at 11 years of age, males had peak incidence 2 years later. These results confirm the low occurrence of Type 1 diabetes in northern Italy. A seasonal variation in onset of Type 1 diabetes was seen.