Paolo Fornengo

Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients.

OBJECTIVE—A protective effect of residual β-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications. RESEARCH DESIGN AND METHODS—We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994–2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated. RESULTS—Residual β-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (β = 0.02; P < 0.0001) and triglycerides (β = 0.20; P = 0.05) and inversely associated with diabetes duration (β = −0.03; P < 0.0001) and HDL cholesterol (β = −0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (<0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37–0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38–1.58]). CONCLUSIONS—Our study shows an independent protective effect of residual β-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest β-cell function over time.

Uric acid is not an independent predictor of cardiovascular mortality in type 2 diabetes: a population-based study.

OBJECTIVE Although some studies have suggested that uric acid is a risk factor for mortality, this relationship is still uncertain in people with type 2 diabetes. METHODS The study base was the population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study. The role of serum uric acid on 15-years all-cause, cardiovascular and non-cardiovascular mortality was assessed by multivariate Cox proportional hazards modeling. RESULTS Baseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome. Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed. Compared to the lower quartile of uric acid, HRs (95% CI) in the upper quartile were 1.47 (1.22-1.76) for all-cause mortality; 1.40 (1.09-1.80) for cardiovascular mortality and 1.50 (1.15-1.96) for non-cardiovascular mortality. In multiple adjusted models, however, HRs were 1.30 (1.06-1.60) for all-cause mortality, 1.13 (0.85-1.50) for cardiovascular mortality and 1.50 (1.11-2.02) for non-cardiovascular mortality (men 1.87, 1.19-2.95; women 1.20, 0.80-1.80); the latter appeared to be due to neoplastic diseases (HR in all combined quartiles vs. lower quartile: both sexes 1.59, 1.05-2.40; men 1.54, 0.83-2.84, women 1.68, 0.95-2.92). CONCLUSIONS In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies.

C-Reactive Protein and 5-Year Survival in Type 2 Diabetes: The Casale Monferrato Study

OBJECTIVE To determine to what extent plasma C-reactive protein (CRP) values influence 5-year all-cause and cardiovascular mortality in type 2 diabetic individuals, independently of albumin excretion rate (AER) and other cardiovascular risk factors, and its incremental usefulness for predicting individual risk of mortality. RESEARCH DESIGN AND METHODS Measurements of CRP were performed in 2,381 of 3,249 (73.3%) subjects as part of the population-based Casale Monferrato Study. Its association with 5-year all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. The C statistic and measures of calibration and global fit were also assessed. RESULTS Results are based on 496 deaths in 11.717 person-years of observations (median follow-up 5.4 years). With respect to subjects with CRP ≤3 mg/l, those with higher values had an adjusted hazard ratio (HR) of 1.51 (95% CI 1.18–1.92) for all-cause mortality and 1.44 (0.99–2.08) for cardiovascular mortality. In normoalbuminuric subjects, respective HRs of CRP were 1.56 (1.13–2.15) and 1.65 (1.00–2.74), AER being neither a modifier nor a confounder of CRP association. In analysis limited to diabetic subjects without cardiovascular disease (CVD), adjusted HRs were 1.67 (1.24–2.24) for all-cause mortality and 1.36 (0.83–2.24) for cardiovascular mortality. The improvement in individual risk assessment was marginal when measured with various statistical measures of model discrimination, calibration, and global fit. CONCLUSIONS CRP measurement is independently associated with short-term mortality risk in type 2 diabetic individuals, even in normoalbuminuric subjects and in those without a previous diagnosis of CVD. Its clinical usefulness in individual assessment of 5-year risk of mortality, however, is limited.

Higher lipoprotein (a) levels in atherothrombotic than lacunar ischemic cerebrovascular disease

Abstract—To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.

Hospital Admissions for Hypertensive Crisis in the Emergency Departments: A Large Multicenter Italian Study

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4–4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06–1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs.

Increased QT Interval Dispersion Predicts 15-Year Cardiovascular Mortality in Type 2 Diabetic Subjects The population-based Casale Monferrato Study

OBJECTIVE To evaluate the predictive role of increased corrected QT (QTc) and QT interval dispersion (QTd) on all-cause and cardiovascular mortality in a large, unselected type 2 diabetic population. RESEARCH DESIGN AND METHODS The prospective study included 1,357 type 2 diabetic patients from the Casale Monferrato Study. At baseline, QTc intervals >0.44 s and QTd intervals >0.08 s were considered abnormally prolonged. Both all-cause and cardiovascular mortality were assessed 15 years after the baseline examination. RESULTS During the follow-up period, 862 subjects per 12,450 person-years died. Multivariate analysis showed that the hazard ratio (HR) of cardiovascular mortality was significantly increased in subjects with prolonged QTd (1.26 [95% CI 1.02–1.55]) and was only slightly reduced after multiple adjustments. Conversely, prolonged QTc did not increase the HRs for all-cause or cardiovascular mortality. CONCLUSIONS Increased QTd predicts cardiovascular mortality after a long-term follow-up period in a large, unselected population of type 2 diabetic subjects.

Apolipoprotein E Polymorphism and Stroke Subtypes in an Italian Cohort

Background: Studies have indicated that apolipoprotein E (ApoE)-ε4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. Methods: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. Results: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-ε4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-ε4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-ε4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-ε4 allele was not significant (OR 1.25, 95% CI 0.57–2.74). Conclusion: Our study shows similar ApoE-ε4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

What is the clinical usefulness of the metabolic syndrome? The Casale Monferrato study.

Objective Data on the clinical usefulness of the metabolic syndrome with respect to cardiovascular risk are not conclusive. We have assessed this issue in a large population-based cohort of diabetic and nondiabetic people in Southern Europe. Methods An Italian population-based cohort of 3729 individuals (2211 without diabetes and 1518 with diabetes) was examined, with centralized measurements, including the Homeostasis Model Assessment (HOMA) index in nondiabetic people. The usefulness of the metabolic syndrome (ATP III criteria) as an indicator of cardiovascular disease (CVD), independently of classical and novel risk factor [C-reactive protein (CRP) and albumin excretion rate (AER)] was assessed by using unconditional logistic regression. Results One thousand, seven hundred and fifty-three individuals (47.0%) had neither diabetes nor the metabolic syndrome, 458 (12.3%) had the metabolic syndrome only, 442 (11.8%) had type 2 diabetes only and 1076 (28.9%) had both diabetes and the metabolic syndrome. The highest likelihood of having CVD was conferred by both diabetes and the metabolic syndrome [odds ratio (OR) = 4.37, 95% confidence interval (CI) 3.25–5.87], independently of age, sex, low-density lipoprotein-cholesterol, smoke, AER, and CRP values. After further adjustment for its individual components, the association between CVD and the metabolic syndrome was no more evident. Among people with CRP 3 mg/l or less, ORs were similar in nondiabetic people with the metabolic syndrome and in diabetic people without it, whereas among those with CRP greater than 3 mg/l OR was two-fold higher in the latter. Values in upper quartiles of the HOMA-IR conferred a significant two-fold increased OR of CVD, even after adjustment for individual components of the metabolic syndrome, CRP and AER. Conclusions The additional information provided by the metabolic syndrome is limited, in both diabetic and nondiabetic people, whereas the HOMA index is a useful indicator of CVD, independently of individual components of the metabolic syndrome, classical and novel risk factors.

Resistant Hypertriglyceridemia in a Patient With High Plasma Levels of Apolipoprotein CII

To the Editor: Human apolipoprotein CII (apo CII) consists of 79 amino acid residues and is required as a cofactor in the hydrolysis of triacylglycerides of chylomicrons and VLDL by lipoprotein lipase.1 2 Familial apo CII deficiency is an autosomal recessive genetic disorder characterized by fasting hypertriglyceridemia and an accumulation of chylomicrons in the plasma.3 Shachter et al4 generated transgenic mice overexpressing human apo CII, and these authors reported the unexpected observation of marked hypertriglyceridemia with an accumulation of triglyceride-enriched VLDL in the plasma. We are the first to report a case of resistant hypertriglyceridemia in a young man with high plasma levels of apo CII (turbidimetric method …

Cryptogenic cerebral infarction in a young patient with very high lipoprotein(a) serum level as the only risk factor

Lipoprotein(a) [Lp(a)] is a plasma lipoprotein that consists of a low-density lipoprotein (LDL)-like particle containing APO B-100 and apolipoprotein(a), linked by a disulphide bridge. There is evidence that higher serum level of Lp(a) is a predictor of various vascular diseases, such as myocardial infarction, coronary stenosis, re-occlusion of aortocoronary bypass vein grafts, peripheral atherosclerosis and cerebral infarction [1–4]. We describe a young man with a cryptogenic stroke with very high serum level of Lp(a) as the only vascular risk factor.