Paolo Cavallo-Perin

Hypertensive Urgencies and Emergencies: Prevalence and Clinical Presentation

The prevalence and clinical picture of hypertensive urgencies and emergencies in an emergency department are poorly known. The aim of the present study was to evaluate the prevalence of hypertensive crises (urgencies and emergencies) in an emergency department during 12 months of observation and the frequency of end-organ damage with related clinical pictures during the first 24 hours after presentation. Hypertensive crises (76% urgencies, 24% emergencies) represented more than one fourth of all medical urgencies-emergencies. The most frequent signs of presentation were headache (22%), epistaxis (17%), faintness, and psychomotor agitation (10%) in hypertensive urgencies and chest pain (27%), dyspnea (22%), and neurological deficit (21%) in hypertensive emergencies. Types of end-organ damage associated with hypertensive emergencies included cerebral infarction (24%), acute pulmonary edema (23%), and hypertensive encephalopathy (16%) as well as cerebral hemorrhage, which accounted for only 4.5%. Age (67 +/- 16 versus 60 +/- 14 years [mean +/- SD], P < .001) and diastolic blood pressure (130 +/- 15 versus 126 +/- 10 mm Hg, P < .002) were higher in hypertensive emergencies than urgencies. Hypertension that was unknown at presentation was present in 8% of hypertensive emergencies and 28% of hypertensive urgencies. In conclusion hypertensive urgencies and emergencies are common events in the emergency department and differ in their clinical patterns of presentation. Cerebral infarction and acute pulmonary edema are the most frequent types of end-organ damage in hypertensive emergencies.

QT interval, cardiovascular risk factors and risk of death in diabetes

A prolonged QT interval is considered an indicator of increased risk of malignant ventricular arrhythmias and/or sudden death. It has been proposed that autonomic neuropathy in diabetes is related to QT interval prolongation and increased mortality rates. Several studies in Type 1 and Type 2 diabetic patients have confirmed the independent relation between prolonged QT interval duration or increased QT interval dispersion and chronic ischemic heart disease. It has been consistently shown that autonomic neuropathy is related to QT interval duration while more controversies exist on the association with QT interval dispersion. In recent years, studies have confirmed the value of QT interval as a predictor of total mortality in both diabetic and non-diabetic subjects. Moreover, several studies have shown a significant relation between QT interval prolongation and cardiovascular disease risk factors. QT interval could be used to stratify the cardiovascular risk in diabetic patients. We still do not know why QT interval is prolonged and how this abnormality leads to death. Nevertheless, QT interval is a simple, low-cost measure, easily obtainable without the need of the patient’s compliance and which could help to select patients who need second level diagnostic procedures and strict observation.

Hypouricemia and hyperuricemia in type 2 diabetes: two different phenotypes.

Background and Design Conflicting data exist about uric acid levels in type 2 diabetes mellitus, as low levels were found in diabetic patients, while elevated serum uric acid is a feature of hyperinsulinemia and impaired glucose tolerance. The present study was addressed to evaluate the relation between uric acid and metabolic parameters, creatinine clearance and albumin excretion rate in a cohort of type 2 diabetic patients.

Low birthweight and metabolic abnormalities in twins with increased susceptibility to Type 2 diabetes mellitus

Aims To evaluate the role of environmental intra‐uterine factors in determining the birthweights of twins with increased susceptibility to diabetes and discordant for abnormal responses to the oral glucose tolerance test (OGTT) and verify the possible association of within‐pair birthweight differences and metabolic abnormalities in adult life.

Prevalence and Risk Factors for Micro- and Macroalbuminuria in an Italian Population-Based Cohort of NIDDM Subjects

OBJECTIVE To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS The prevalences of microalbuminuria (AER 20–200 μg/min), macroalbuminuria (AER > 200 μg/min), and hypertension were 32.1% (95% CI 29.8–34.4), 17.6% (15.7–19.5), and 67% (64.6–69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04–1.66 for microalbuminuria and OR 1.63, 1.22–2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.

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‐.

PAI-1 and Factor VII Activity Are Higher in IDDM Patients With Microalbuminuria

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD) in insulin-dependent diabetes mellitus (IDDM) patients, but the pathophysiological basis of this association is not clear. To see whether or not hemostatic dysfunctions might contribute to explain this association, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), factor VII activity, plasma fibrinogen, and plasma endothelin-1 (ET-1) in 13 microalbuminuric (albumin excretion rate [AER], 20–200 μg/min) and in 13 comparable normoalbuminuric (< 20 μg/min) IDDM patients. t-PA and ET-1 were similar in the two groups, whereas PAI-1 activity (5.65 ± 1.92 vs. 0.85 ± 0.58 IU/ml, P < 0.05), factor VII (87.85 ± 4.94 vs. 76.54 ± 2.31%, P < 0.05), and plasma fibrinogen (3.38 ± 0.21 vs. 2.65 ± 0.13 g/l, P < 0.05) were significantly higher in microalbuminuric than in normoalbuminuric patients. Plasma fibrinogen was related to AER (r2 = 0.23, P < 0.05), whereas triglycerides and factor VII were related to PAI-1 (r2 = 0.39, P < 0.001 and r2 = 0.10, P < 0.05). These results suggest that microalbuminuria is associated with a hypercoagulative and hypofibrinolytic state. Hemostatic dysfunctions might be a pathogenetic link between microalbuminuria and CVD.

Insulin resistance and hyperinsulinemia in homozygous β-thalassemia☆

Abstract Insulin resistance and hyperinsulinemia have been reported in homozygous β-thalassemia before the development of diabetes. However, insulin sensitivity (S l ) has never been studied in normoinsulinemic patients. Furthermore, whether hyperinsulinemia is due to increased β-cell secretion or to decreased hepatic insulin extraction is poorly understood. We estimated S l β-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (2.8 g/m 2 ) in two groups of nondiabetic pubertal patients with homozygous β-thalassemia (seven hyperinsulinemic and seven normoinsulinemic patients) and seven control subjects matched for age, body mass index, and pubertal stage. In both thalassemic groups, S l was reduced by approximately 40% (3.52 ± 0.57 and 3.74 ± 0.66 v 6.89 ± 1.02 10 −4 · min − [μU/mL], P = .011) and was inversely correlated with iron overload ( r = −.707, P = .006). All parameters of β-cell secretion were not significantly different in patients and controls. On the other hand, basal posthepatic insulin delivery (BDR) was more than doubled in hyperinsulinemic patients with respect to normoinsulinemic patients or controls (15.1 ± 2.4 v 6.1 ± 1.1 and 7.5 ± 2.3 pmol/L · min −1 , P = .012), and the same was true for total posthepatic insulin delivery ([TID] 6.3 ± 1.0 v 2.9 ± 0.5 and 2.9 ± 0.7 pmol/L · 240 min −1 , P = .015). Hepatic insulin extraction was significantly lower in hyperinsulinemic patients than in normoinsulinemic patients or controls (49.3% ± 9.4% v 73.0% ± 3.7% and 77.4% ± 3.9%, P = .011), and in patients it was inversely correlated with iron overload ( r = −.829, P = .0001). In conclusion, insulin resistance is present even in normoinsulinemic patients, β-cell responsiveness to glucose is normal, and hyperinsulinemia is mainly due to decreased hepatic insulin extraction. In nondiabetic thalassemic patients, these defects are possibly related to iron overload.

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.