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.

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.

Clinical, immunological, and genetic heterogeneity of diabetes in an Italian population-based cohort of lean newly diagnosed patients aged 30-54 years. Piedmont Study Group for Diabetes Epidemiology.

OBJECTIVE: In lean diabetic patients, the presentation of the disease does not allow one to easily distinguish between type 1 and type 2. Aims of this study were to describe clinical, immunological, and genetic features of lean newly diagnosed diabetic patients. RESEARCH DESIGN AND METHODS: A population-based cohort of 130 lean (BMI < 25 kg/m2) newly diagnosed patients, aged 30-54 years, was identified among residents of the province of Turin. Islet cell antibodies (ICAs), anti-GAD, fasting and glucagon-stimulated C-peptide values, and HLA DQA1-DQB1 susceptibility genotypes were assessed within 2 months of the diagnosis. RESULTS: A total of 45 (34.6%) and 29 (22.3%) patients were, respectively, ICA+ and anti-GAD+, with 15 (11.5%) having both antibodies. In 59 patients, ICAs and/or anti-GAD antibodies were detected, giving a high prevalence of autoimmunity (45.4%, 95% Cl 36.8-54.0); relative to patients without markers (n = 71), they were younger (40.8 +/- 7.5 vs. 45.0 +/- 6.5 years, P < 0.001) and showed lower values of fasting C-peptide (0.56 +/- 0.33 vs. 0.79 +/- 0.41 nmol/l, P < 0.001) and stimulated C-peptide (1.03 +/- 0.56 vs. 1.42 +/- 0.69 nmol/l, P < 0.001). The lowest stimulated C-peptide values were found in patients with both ICA and anti-GAD antibodies. Frequencies of adult-onset type 1 and type 2 diabetes were, respectively, 49.2 and 50.8%. Clinical and genetic features were not useful in the classification of patients. CONCLUSIONS: Almost 50% of lean young and middle-aged patients were ICA+ and/or anti-GAD+, suggesting a high prevalence of a slowly evolving form of type 1 diabetes. The evaluation at diagnosis of both beta-cell secretory capacity and markers of autoimmunity is recommended to provide a pathogenetic classification of the disease.

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.

Physiological inhibitors of blood coagulation and prothrombin fragment F 1 + 2 in type 2 diabetic patients with normoalbuminuria and incipient nephropathy.

Microalbuminuria and haemostasis derangements have been considered as independent risk factors for cardiovascular death in type 2 (non-insulin-dependent) diabetic patients. Few studies have assessed coagulation inhibitors in type 2 diabetic patients with normoalbuminuria and microalbuminuria. Therefore, 32 type 2 diabetic patients with normoalbuminuria (albumin excretion rate, AER < 20 mg/min, mean 7 +/- 1) and 28 type 2 diabetic patients with microalbuminuria (AER 20-200 mg/min, mean 84 +/- 11) were studied. The patients were matched for age, sex, disease duration and treatment, body mass index (BMI), blood pressure and glycohaemoglobin. Protein C and S activity, antithrombin III, thrombomodulin and prothrombin fragments 1 + 2 (F 1 + 2) were assessed together with fibrinogen, triglycerides, total and high density lipoprotein (HDL)-cholesterol concentrations. Fibrinogen, total and low density lipoprotein (LDL) concentrations were similar in the two groups, while a significant difference was observed for triglycerides (normoalbuminuric group: 128 +/- 10 mg/dl, microalbuminuric group: 184.1 +/- 17 mg/dl; P < 0.007) and HDL-cholesterol (normoalbuminuric group: 45 +/- 2 mg/dl, microalbuminuric group: 39 +/- 2 mg/dl; P < 0.05). The coagulation parameters were as follows: normoalbuminuric group: protein C activity 109% +/- 5%, protein S 95.4% +/- 5%, thrombomodulin 49.3 +/- 3 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.05 +/- 0.04 nmol/l; microalbuminuric group: protein C activity 107% +/- 4%, protein S 98.4% +/- 4%, thrombomodulin 64.4 +/- 4 ng/ml, antithrombin III 93.3% +/- 3%, F 1 + 2 1.03 +/- 0.05 nmol/l. The difference was significant for thrombomodulin (P < 0.007). A significant direct correlation was observed in the microalbuminuric group between AER and thrombomodulin (r = 0.38, P < 0.05). In conclusion, our data do not support the hypothesis that a reduction in the activity of anticoagulant physiological inhibitors (protein C, protein S, antithrombin III) could contribute to explain the higher cardiovascular risk in type 2 diabetic patients with microalbuminuria. The elevation of plasma thrombomodulin concentration in type 2 diabetic patients could be the consequence of widespread vascular damage in diabetic patients with incipient nephropathy.

Anticoagulant protein C activity in non-insulin-dependent diabetic patients with normoalbuminuria and microalbuminuria.

Microalbuminuria in diabetic patients is associated with an increased cardiovascular risk which is not completely explained by an excess of conventional cardiovascular risk factors. A depression of physiologic inhibitors of blood coagulation could contribute to a thrombophilic state and to cardiovascular complications: data on protein C in diabetic patients are controversial, and no information exists about protein C activity in non-insulin-dependent diabetic patients or its relation to the microalbuminuric state. The aim of this study was to assess protein C activity in non-insulin-dependent diabetic patients with and without microalbuminuria. Protein C activity was determined (Protein C Reagent, Boehringer Mannheim, Germany) in 29 non-insulin-dependent diabetic patients with microalbuminuria (group A, > 20 micrograms/min), 33 non-insulin-dependent diabetic patients with normoalbuminuria (group B), and in 36 non-diabetic healthy blood donors as a control group (group C). The groups were matched for sex, and no difference in age, body mass index, blood pressure, glycated haemoglobin or known duration of diabetes was observed between groups A and B. Protein C activity was similar in the three groups (mean +/- SD): group A, 106.9% +/- 25.2%; group B, 109.3% +/- 27.6%; group C, 103.1% +/- 18.9%; F value 0.58, NS. Protein C activity did not correlate significantly with body mass index, glycated haemoglobin, known duration of diabetes, age or albumin excretion rate in any of the groups or in the diabetic patients as a whole. No significant difference in protein C activity was observed in patients taking other therapy (diet, oral agents, insulin).(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic nervous activity in obese subjects before and after caloric restriction.

The heart rate response to deep breathing (DB test) and standing (30:15 r test) and the blood pressure response to standing (LS test) and sustained handgrip (HG test) were assessed in 19 obese subjects and 15 age matched lean controls. The results of DB, 30:15 r and LS tests were not significantly different in both groups. The diastolic blood pressure increase during handgrip was significantly higher in obese than in control subjects. After a period of caloric restriction the tests were repeated in 9 patients who had obtained a weight loss of at least 5 kg: a significant decrease in heart rate, diastolic blood pressure and 30:15 r results was observed, whereas the caloric restriction did not cause significant variations in the results of DB, LS and HG tests. Our results suggest that in obese patients some autonomic nervous changes can occur before and after weight loss.