QT interval prolongation and mortality in type 1 diabetic patients: a 5-year cohort prospective study. Neuropathy Study Group of the Italian Society of the Study of Diabetes, Piemonte Affiliate.

OBJECTIVE: The aim of the study was to assess the relationship between QT interval prolongation and mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Data on survival after 5 years were obtained from 316 of 379 patients (83.3%) who took part in a study on the prevalence of diabetic neuropathy and QT interval prolongation. RESULTS: Mortality at 5 years was 6.32%. Patients who survived were significantly younger (P = 0.04), had a shorter duration of diabetes (P = 0.01), had lower systolic (P = 0.004) and diastolic (P = 0.03) blood pressure levels, and had a shorter QT interval corrected for the previous cardiac cycle length (QTc) (P = 0.000005) than subjects who died. In univariate analysis, patients had a higher risk of dying if they had a prolonged QTc (odds ratio [OR] 20.14 [95% CI 5.7-70.81) or if they were affected by autonomic neuropathy (3.55 [1.4-8.9]). QTc prolongation was the only variable that showed a significant mortality OR in multivariate analysis (24.6 [6.51-92.85]; P = 0.0000004). CONCLUSIONS: This is the first cohort-based prospective study indicating that QTc prolongation is predictive of increased mortality in type 1 diabetic patients.

Comparison of the cost-effectiveness of three approaches to screening for and treating sight-threatening diabetic retinopathy.

The purpose of this study was to analyse and compare the costs involved in screening for and treating sight-threatening diabetic retinopathy in three different clinical settings. In the first setting, diabetologists screened using ophthalmoscopy and color photography, according to the St. Vincent Declaration guidelines, and selected patients for further assessment by a visiting ophthalmologist and for treatment in another hospital. In the second setting, all patients were regularly referred to ophthalmologists, either in the same hospital or elsewhere, for all aspects of eye care. In the third setting, screening was done again with ophthalmoscopy alone by diabetologists who followed the St. Vincent Declaration guidelines; however, further assessment and treatment were carried out in the eye department of the same hospital. Costs to the Italian National Health Service and to patients were calculated per screening performed and per patient subjected to laser treatment as a result of screening. A sensitivity analysis was then performed to simulate the costs of standardised patient populations going through the three different settings. It is concluded that absolute costs would be lower, both for the Italian National Health Service and for patients, if screening, assessment and treatment were all carried out in the same hospital. Equipping a diabetic clinic specially for screening would not be more expensive than delegating eye care to external parties, even for a hospital without an eye department. Moreover, delegating eye care more than doubles costs for patients. Screening for, assessing and treating sight-threatening diabetic retinopathy may be a cost-effective procedure for society as a whole in Italy.

Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy.

Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors in poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (> 20 micrograms/min) or normal albumin excretion rate (< 20 micrograms/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7 +/- 1.2 vs 3.4 +/- 0.6 micrograms/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.

Circadian blood pressure levels in normotensive normoalbuminuric type 1 diabetic patients.

Increase in blood pressure and its circadian alterations in Type 1 diabetes are usually associated with diabetic nephropathy. To evaluate if diabetes itself could be responsible for the observed increase in blood pressure levels, we studied a group of 17 normotensive, normoalbuminuric Type 1 diabetic patients with a disease duration more than 15 years, with no clinical evidence of autonomic neuropathy or ischaemic heart disease, and without any known determinant of hypertension, and a control group of 17 normal subjects, normotensive, each matched for sex, age, BMI, albumin excretion rate, and clinical blood pressure to a diabetic subject. In both groups an ambulatory blood pressure monitoring was performed through an oscillometric recorder. The mean systolic and diastolic ambulatory blood pressure values were significantly higher in diabetic patients (p < 0.001) in the 24-h analysis and during waking and sleeping periods. The night/day ratio of systolic and diastolic blood pressure were not significantly different in patients and controls, as well as heart rate values and heart rate variability. We conclude that mechanism(s) inherent to the diabetic condition other than diabetic nephropathy or autonomic neuropathy could be responsible for blood pressure evaluation in normotensive Type 1 diabetes with normoalbuminuria.

Prevalence of QT prolongation in a type 1 diabetic population and its association with autonomic neuropathy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes.

The prevalence of QT prolongation in a large random sample of Type 1 diabetic patients in Piemonte, Italy and its association with autonomic neuropathy were assessed. Three hundred and seventy-nine Type 1 diabetic patients (age 15-59) with (94, DAN+) and without (280, DAN-) autonomic neuropathy and 118 non-diabetic control subjects participated in the study. QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazett's formula. QTc was greater than 0.440 s in 7.6% (95% CI 2.9-12.3) of control subjects, 25.6% (21.0-30.0) of diabetic patients, 30.8% (21.5-40.1) of DAN+, 23.9% (18.9-28.9) of DAN-. QTc was greater than 0.460 s (mean + 2SD of QTc in control subjects) in 11.7% (8.5-14.9) of diabetic patients, 18.1% (10.3-25.9) of DAN+, 9.6% (6.2-13.0) of DAN-. QT was above the 95% upper limit for the control subjects in the plot of measured QT against RR interval in 21.4% (17.3-25.5) of diabetic patients, 26.6% (17.7-35.5) of DAN+, 19.3% (14.7-23.9) of DAN-. No correlation was found between QT interval and age or disease duration. The prevalence of QT prolongation was higher in diabetic patients than in control subjects and in DAN+ than in DAN-.

Prevalence of neuropathy in IDDM patients in Piemonte, Italy. The Neuropathy Study Group of the Italian Society for the Study of Diabetes, Piemonte Affiliate.

OBJECTIVE: In view of the scarce data available in Italy, to assess the prevalence of neuropathy in various subgroups of IDDM patients living in the Piemonte region of Italy and to develop, based on existing guidelines, and test the practicality of a standardized assessment of diabetic neuropathy. RESEARCH DESIGN AND METHODS: All IDDM patients (766) attending 23 outpatient clinics, evenly distributed in the region, were stratified into 3 age-groups (15-29, 30-44, and 45-59 yr) and into 3 groups of diabetes duration (1-7, 8-14, and > or = 15 yr). A random sample of 467 patients was selected; 81% of whom participated in the studies (196 men and 183 women). The following data were collected: personal and clinical data, structured questionnaire (SQ), neurological examination (NE), vibration sensation (tuning fork) (VS), and two cardiovascular tests (CTs). Patients were classified as follows: stage 0, (no neuropathy) < 2 abnormalities among SQ, NE, VS, and CT; stage 1, (asymptomatic neuropathy) > 1 abnormality among NE, VS, and CT; stage 2, (symptomatic neuropathy) abnormalities in SQ and in NE, and/or VS, and/or CT. RESULTS: The prevalence rates were as follows: stage 0 = 71.5%, stage 1 = 7.2%, and stage 2 = 21.3% and all had a 95% CI. No difference was found between men and women. The prevalence of neuropathy (stages 1 and 2) was higher (P < 0.01) in groups of longer diabetes duration or older age. CONCLUSIONS: Polyneuropathy is a frequent complication in a north Italian IDDM population. Our results suggest that IDDM patients > 30 yr of age, with diabetes of > 15 yr duration, and who complain of symptoms suggestive of neuropathy, should be promptly assessed for the presence of diabetic polyneuropathy.

[Neurologic manifestations of lupus erythematosus]. / Manifestazioni neurologiche in corso di lupus.

A nervous system involvement is common in systemic lupus erythematosus, and may be the initial manifestation of the disease. The spectrum of nervous system involvement is wide, and encompasses almost the whole range of neurological diseases. The neurological lupus is divided into a primary and a secondary group, and in the latter the pathogenetic role is supported by drugs and by organic and functional changes in the other organs and systems. In secondary neurological lupus, when a clinical picture of a focal cerebral injury is sustained by the presence of lupus anticoagulants, the prognosis is strict and the treatment problematic. Finally, among the primary neurological lupus it is important to distinguish two subsets of acute and subacute neurological lupus, because of differences in its management and prognosis.

Hyperprolactinemia in girls with idiopathic precocious puberty under prolonged treatment with cyproterone acetate.

Pasma prolactin response to the acute injection of sulpiride (1.5 mg/k BW im) was measured at 0800-0900h in 4 girls with idiopathic precocious puberty before and after 6 to 11 months of continuous therapy with 50 mg daily of cyproterone acetate (CA) orally administered. Two additional girls were examined after 26 and 28 months of therapy, respectively. Mean baseline prolactin concentrations were significantly higher in untreated girls with precocious puberty as compared to that of normal controls of the same chronological age and of a comparable degree of sexual maturation (14.5 +/- 1.9 SE vs. 7.4 +/- 1.8 SE ng/ml and vs. 9.5 +/- 1.8 ng/ml, respectively; P less than .02). Treatment with CA caused a significant further increase of plasma prolactin concentration (P less than .02 as compared to pre-treatment values); no correlation was observed between prolactin concentration and duration of treatment. No significant change in the integrated areas of prlactin response to sulpiride occurred after prolonged CA therapy. The results suggest that in idiopathic precocious puberty the action of CA upon the hypothalamic-hypophyseal complex is not solely antigonadotropic and that prolactin secretion is enhanced in patients given this drug.