M. Veglio

Prevalence of QT Prolongation in a Type 1 Diabetic Population and Its Association with Autonomic Neuropathy

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 Bazetts 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‐.

FINE-NEEDLE ASPIRATION BIOPSY OF THE THYROID: COMPARISON BETWEEN THYROID PALPATION AND ULTRASONOGRAPHY

OBJECTIVE To describe our experience with fine-needle aspiration biopsy (FNAB) of the thyroid and compare our results with direct palpation versus ultrasound scanning (USS) in an area of endemic goiter in Italy. METHODS We considered all patients submitted to ultrasound-guided FNAB of thyroid nodules during a 10-month period at our outpatient clinic and analyzed the following: (1) clinical data (number of nodules and identification of the nodule for FNAB); (2) USS data (number of nodules and identification of the nodule for FNAB on the basis of hypoechoic pattern + blurred perinodal halo + microcalcifications or intranodal color Doppler signal indicative of blood flow); (3) cytologic specimens, categorized as suspicious, malignant, negative, or nondiagnostic; and (4) histologic final report of the cytologically positive nodules. RESULTS The study group consisted of 348 female and 72 male patients who underwent FNAB of the thyroid at our institution. Among the 140 patients with no palpable thyroid nodules, USS showed that 106 had a single nodule and 34 had multinodular goiters. Among the 182 patients with a single palpable thyroid nodule, USS revealed that 138 had a single nodule, 42 had a multinodular goiter, and 2 had lobe enlargement without detectable nodules. All 98 patients with multinodular palpable goiter had a similar pattern on USS. Of the 420 cytologic specimens, 46(11.0%) were positive for thyroid cancer, 313 (74.5%)were negative, and 61 (14.5%) were nondiagnostic. Histologic malignant growth was confirmed in 27 cytologically positive nodules. Of these histologically malignant nodules, 12 (45%) were nonpalpable, 9 (33%) were single palpable nodules, and 6 (22%) were from a nodule with a suspicious ultrasound pattern within a multinodular goiter. CONCLUSION Manually guided FNAB is not feasible in nonpalpable nodules and not accurate in a multinodular goiter. Both situations are clinical challenges, and USS should be performed for accurate FNAB under these circumstances. Because 52% of histologically malignant nodules in our study were found only with the aid of ultrasound-guided FNAB, this procedure should be used where multinodular goiter is endemic. Our overall rate of nondiagnostic specimens was comparable to that reported in the literature.

Does Abnormal QT Interval Prolongation Reflect Autonomic Dysfunction in Diabetic Patients? QTc Interval Measure Versus Standardized Tests in Diabetic Autonomic Neuropathy

The question as to whether the QTc interval correlates with five cardiovascular tests (deep breathing test, 30/15 ratio test, lying to standing test, cough test, and postural blood pressure test) for the diagnosis of diabetic autonomic neuropathy (DAN) was investigated in 168 (38 Type 1, 130 Type 2) consecutive outpatients (mean age 54.9 ± 11.2 years). QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazetts formula. The percentage of patients with a QTc greater than 0.440 s was: absent DAN = 11% (n = 7), probable DAN = 7% (n = 4), definite DAN = 23% (n = 12) (p < 0.05), and the mean (± SD) QTc values were 0.403 ± 0.028 s, 0.405 ± 0.023 s, and 0.421 ± 0.026 s, respectively. A significant correlation between QTc duration and DAN score of autonomic cardiovascular test results (r = 0.34, p < 0.0001) was observed. The calculated specificity, sensitivity, positive and negative predictive values were 89%, 15%, 70% and 37%, respectively. In conclusion, QTc can be considered as an additional specific test in the assessment of diabetic autonomic neuropathy, but cannot replace the standard battery of cardiovascular tests.

INCIDENCE AND RISK FACTORS OF PROLONGED QTc INTERVAL IN TYPE 1 DIABETES: THE EURODIAB PROSPECTIVE COMPLICATIONS STUDY.

OBJECTIVE—Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and diabetic populations. As part of the EURODIAB Prospective Complication Study, we have assessed the 7-year incidence and risk factors of prolonged QTc in people with type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 1,415 type 1 diabetic subjects, who had normal QTc at baseline, were reanalyzed after the 7-year follow-up period. QTc >0.44 s was considered abnormally prolonged. RESULTS—Cumulative incidence of prolonged QTc was 18.7%, which is twofold higher in women than in men (24.5 vs. 13.9%, P < 0.0001). At the baseline examination, incident cases were older and less physically active than nonincident cases, had higher mean values of systolic blood pressure and HDL cholesterol, and had higher frequencies of hypertension, coronary heart disease, and distal symmetrical polyneuropathy. In multivariate logistic regression analyses, female sex and higher values of A1C and systolic blood pressure were associated with the risk of prolonged QTc, whereas physical activity and BMI within the range of 21.5–23.2 kg/m2 were protective factors. In women, association with modifiable factors, particularly BMI, was stronger than in men. CONCLUSIONS—In type 1 diabetic subjects from the EURODIAB cohort, female sex, A1C, and systolic blood pressure are predictive of prolonged QTc, whereas physical activity and BMI within the range of 21.5–23.2 kg/m2 play a protective role. These findings are clinically relevant, as they may help to identify subjects at higher risk for prolonged QTc, as well as provide potential targets for risk-lowering strategies.

Autonomic neuropathy and QT interval in hemodialysed patients.

Abstract.Background QT interval prolongation increases the risk of ventricular arrhythmias and sudden death in diabetic autonomic neuropathy and ischemic heart disease. In end–stage renal disease (ESRD), the effects of hemodialysis on QT interval are diverse and the influence of autonomic neuropathy has yet to be clearly defined.MethodsSixty–nine ERSD patients (age 64 ± 14) were studied. Prior to the dialysis session, patients underwent four standard autonomic cardiovascular tests; before and after the dialysis session, a 12–lead ECG was recorded. Corrected QT intervals (QTc) were measured and QT dispersion (QTd) was calculated. Twelve subjects (age 59 ± 6) with normal renal function served as control group.ResultsCompared to controls, ESRD patients showed a longer QTc (434 ± 26 vs 414 ± 28ms; p = 0.016) and a similar QTd (35 ± 13 vs 37 ± 14ms; p = 0.54).QTc was > 440ms in 33.3% of the patients. No difference in the prevalence or score of autonomic neuropathy was observed between the subgroups with and without a prolonged QTc. After the hemodialysis session, QTc increased in 56% and decreased in 43% of the patients, and QTd increased in 45 % and decreased in 55% of the patients. QTc and QTd changes were not related to the presence of autonomic neuropathy.ConclusionsA large variability in QTc and QTd response was observed after hemodialysis. Autonomic neuropathy did not contribute to QTc and QTd length, nor to QTc and QTd change after dialysis.

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-insulindependent 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 μg/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). In conclusion, our data do not support the hypothesis that a reduction of the anticoagulant protein C contributes to the higher cardiovascular risk of non-insulin-dependent diabetic patients compared with control subjects and of patients with microalbuminuria compared with those without.