Giacomo Zoppini

Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients.

CONTEXT A strong independent association has been recently observed between elevated red blood cell distribution width (RDW) and increased incidence of cardiovascular events. OBJECTIVE To assess whether RDW is associated with plasma markers of inflammation since the mechanism(s) underlying this association remain unknown. DESIGN We retrospectively analyzed results of RDW, hemoglobin, mean corpuscular volume, ferritin, high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate (ESR) in a large cohort of unselected adult outpatients who were consecutively referred by general practitioners for routine medical check-up. RESULTS Cumulative results of RDW and other factors were retrieved from the database of our laboratory information system for 3845 adult outpatients during a 3-year period. When participants were grouped according to RDW quartiles, there were strong, graded increases of ESR and hsCRP (P < .001), both parameters being up to 3-fold higher in the fourth versus the first quartile. Accordingly, the percentages of those with hsCRP greater than 3 mg/L (from 28% to 63%; P < .001) and ESR greater than 40 mm/h (from 8% to 40%; P < .001) increased steadily across RDW quartiles. In multivariable regression analysis, ESR and hsCRP predicted RDW independently of age, sex, mean corpuscular volume, hemoglobin, and ferritin. CONCLUSIONS To our knowledge, our study demonstrates for the first time a strong, graded association of RDW with hsCRP and ESR independent of numerous confounding factors. If confirmed in future follow-up studies, this association might provide a rationale to introduce the easy, inexpensive RDW in algorithms for cardiovascular risk prediction.

NASH predicts plasma inflammatory biomarkers independently of visceral fat in men.

We assessed the differential contribution of nonalcoholic steatohepatitis (NASH) and visceral adiposity to nontraditional cardiovascular risk biomarkers in adult men. We enrolled 45 consecutive, overweight, male patients with biopsy‐proven NASH, 45 overweight male patients without ultrasound‐diagnosed hepatic steatosis, and 45 healthy male volunteers. All participants were matched for age; NASH and overweight patients were also matched for BMI and visceral adiposity (as estimated by abdominal ultrasonography). Nontraditional cardiovascular risk biomarkers were measured in all participants. Plasma concentrations of high‐sensitivity C‐reactive protein (hs‐CRP), fibrinogen, plasminogen activator inhibitor‐1 (PAI‐1) activity, and adiponectin were markedly different among the groups; the lowest values (the highest for adiponectin) were in nonobese healthy subjects, intermediate in overweight nonsteatotic patients, and the highest (the lowest for adiponectin) in those with biopsy‐proven NASH. The marked differences in these cardiovascular risk biomarkers that were observed between overweight and NASH patients were only slightly weakened after adjustment for age, BMI, smoking, plasma triglycerides, and insulin resistance (IR) as assessed by homeostasis model assessment (HOMA). In multivariate regression analysis, NASH and visceral adiposity predicted cardiovascular risk biomarkers independently of potential confounders. In conclusion, our results suggest that NASH can predict a more atherogenic risk profile in a manner that is partly independent from the contribution of visceral adiposity in adult men.

Non-alcoholic fatty liver disease in patients with chronic plaque psoriasis

BACKGROUND/AIMS Non-alcoholic fatty liver disease (NAFLD) and chronic plaque psoriasis are both associated with metabolic syndrome and increased risk of incident cardiovascular disease. We assessed the frequency and characteristics of NAFLD in patients with chronic plaque psoriasis. METHODS One hundred and thirty consecutive patients with chronic plaque psoriasis and 260 apparently healthy controls matched for age, sex and body mass index were enrolled. NAFLD was diagnosed by abdominal ultrasound after excluding other secondary causes of chronic liver disease. RESULTS The frequency of NAFLD was remarkably greater in psoriasis patients than in controls (47% vs. 28%; p<0.0001). Patients with psoriasis and NAFLD (n=61) were more likely to have metabolic syndrome and had higher serum C-reactive protein concentrations and greater severity of psoriasis according to the Psoriasis Area and Severity Index (PASI) score (14.2+/-12.6 vs. 9.6+/-7.4; p<0.01) than those with psoriasis alone (n=69). In a subgroup of psoriasis patients (n=43), those with NAFLD (n=21) also had significantly higher serum interleukin-6 and lower serum adiponectin levels. Notably, in multivariate regression analysis, NAFLD was associated with higher PASI score independently of age, gender, body mass index, psoriasis duration, and alcohol consumption. CONCLUSIONS NAFLD is frequent in patients with chronic plaque psoriasis - affecting up to nearly half of these patients - and is strongly associated with psoriasis severity. Early recognition of NAFLD by radiological imaging tests in this group of patients is warranted.

Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease

Objectives  To explore associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease (NAFLD).

The Verona diabetes study: a population-based survey on known diabetes mellitus prevalence and 5-year all-cause mortality

SummaryThis population-based survey aimed to determine the prevalence of known diabetes mellitus on 31 December 1986, and to assess all-cause mortality in the subsequent 5 years (1987–1991) in Verona, Italy. In the study of prevalence, 5996 patients were identified by three independent sources: family physicians, diabetes clinics, and drug prescriptions for diabetes. Mortality was assessed by matching all death certificates of Verona in 1987–1991 with the diabetic cohort. Overall diabetes prevalence was 2.61% (95% confidence interval 2.56–2.67). Prevalence of insulin-dependent and non-insulin-dependent diabetes mellitus was 0.069% (0.059–0.078) and 2.49% (2.43–2.54), respectively. Diabetes prevalence sharply increased after age 35 years up to age 75–79, and finally declined. Prevalence was higher in men up to age 69 years, in women after age 75 years. Of the diabetic cohort 1260 patients (592 men, 668 women) died by 31 December 1991, yielding an overall standardized mortality ratio of 1.46 (CI 1.38–1.54). Even though the differences narrowed with age, mortality rates in the diabetic cohort were higher than in the non-diabetic population at all ages. Women aged 65–74 years showed observed/expected ratio higher than men (2.27, CI 1.92–2.66, vs 1.50, CI 1.30–1.72), while in other age groups the sex-related differences were not significant. Pharmacological treatment of diabetes was associated with an excess mortality, while treatment with diet alone showed an apparent protective effect on mortality (observed/expected ratio 0.73, CI 0.58–0.92). In conclusion, in Verona diabetes has a prevalence similar to that of other European countries, and is associated with an excess mortality which is observed in both sexes, at all ages, and with any anti-diabetic pharmacologic treatment. Diet-treated diabetes seems to be associated with a significant reduction in the mortality risk.

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).

Although lifestyle interventions are considered the first‐line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4‐month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual‐energy X‐ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in‐opposed‐phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] −32.8% [−58.20 to −7.52] versus −25.9% [−50.92 to −0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one‐quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups. Conclusion: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD. (Hepatology 2013;58:1287–1295)

Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes.

BACKGROUND & AIMS To estimate the prevalence of non-alcoholic fatty liver disease (NAFLD) in type 1 diabetic individuals, and to evaluate whether NAFLD is associated with increased prevalence of cardiovascular disease (CVD). METHODS All patients with diagnosed type 1 diabetes with available liver ultrasound data (n=250), who regularly attended our diabetes clinic, were enrolled. Main study measures were detection of NAFLD (by patient history and liver ultrasound) and asymptomatic/symptomatic CVD (by patient history, chart review, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries). RESULTS The prevalence of NAFLD was 44.4%, and NAFLD was the most common cause (69.8%) of hepatic steatosis on ultrasound examination. Patients with NAFLD had a remarkably higher (p<0.001) age- and sex-adjusted prevalence of coronary (10.8% vs. 1.1%), cerebrovascular (37.3% vs. 5.5%) and peripheral (24.5% vs. 2.5%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD (as composite endpoint), independently of age, sex, diabetes duration, hemoglobin A(1c), smoking history, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and medication use (adjusted odds ratio 7.36, 95% confidence intervals 1.60-34.3, p<0.01). CONCLUSIONS Our findings suggest that NAFLD is very common in type 1 diabetic subjects and is associated, independently of several confounding factors, with a higher prevalence of CVD. Future prospective studies are needed to evaluate whether NAFLD predicts incident CVD events in type 1 diabetes.

Non-alcoholic hepatic steatosis and its relation to increased plasma biomarkers of inflammation and endothelial dysfunction in non-diabetic men. Role of visceral adipose tissue

Aims  To compare plasma biomarkers of inflammation and endothelial dysfunction in individuals with and without non‐alcoholic hepatic steatosis (HS), and to evaluate whether such differences were mediated by the adverse metabolic pattern, typically found in these subjects.

Prevalence of Subclinical Hypothyroidism in Patients with Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR. RESULTS Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR <60 ml/min per 1.73 m(2). The prevalence of subclinical primary hypothyroidism increased from 7% at an estimated GFR >or=90 ml/min per 1.73 m(2) to 17.9% at an estimated GFR <60 ml/min per 1.73 m(2) (P < 0.0001 for trend). Compared with participants with an estimated GFR >or=60 ml/min per 1.73 m(2), those with estimated GFR <60 ml/min per 1.73 m(2) had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations. CONCLUSIONS These findings suggest that subclinical primary hypothyroidism is a relatively common condition ( approximately 18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.

Long-term Instability of Fasting Plasma Glucose, a Novel Predictor of Cardiovascular Mortality in Elderly Patients With Non–Insulin-Dependent Diabetes Mellitus The Verona Diabetes Study

BACKGROUND We recently reported that long-term fasting plasma glucose (FPG) instability predicts all-cause mortality in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM). The aim of the present study was to evaluate whether glucose instability, as represented by the coefficient of variation of FPG concentrations (CV-FPG) measured during a 3-year period, can predict specific causes of death in the subsequent 5 years. METHODS AND RESULTS Five hundred sixty-six elderly patients with NIDDM were followed up for 5 years to assess mortality and causes of death. All FPG determinations of the 3 years preceding the follow-up available in the clinical records were collected and analyzed. Patients were grouped in tertiles of mean FPG, CV-FPG, and the slope of FPG. These parameters of glucose control, as well as sex, age, duration of diabetes, insulin treatment, cigarette smoking, hypertension, and total cholesterol, were included in a multivariate analysis of mortality. During the follow-up, 63 men and 128 women died. Diabetes- and malignancy-related mortality were not independently associated with any parameter of glucose control, whereas cardiovascular-related mortality was independently associated with CV-FPG (P=.007) but not with the mean or the slope of FPG. In particular, the relative risk of cardiovascular mortality in subjects in tertile III versus tertile I of CV-FPG was 2.40 (95% CI, 1.28 to 4.53). CONCLUSIONS These results indicate that FPG instability is a predictor of cardiovascular-related mortality in elderly patients with NIDDM and suggest that glucose stability might be a goal in the management of these patients.