Paola Andreozzi

Mediterranean Dietary Pattern Adherence: Associations with Prediabetes, Metabolic Syndrome, and Related Microinflammation

BACKGROUND The adherence to the Mediterranean Diet (Med Diet) seems to reduce the incidence of metabolic syndrome. The present study aimed to explore whether the adherence to the overall Med Diet pattern and to specific Med Diet items is associated with the presence of metabolic syndrome, impaired fasting glucose (IFG), insulin resistance (IR), and microinflammation in subjects free of diabetes and cardiovascular diseases. MEASUREMENTS Each patient underwent clinical assessment. Adherence to the Med Diet was measured by a previously validated 14-item questionnaire. Metabolic syndrome was defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria; IR was defined by homeostasis model assessment of insulin resistance (HOMA-IR); inflammation was assessed through a high-sensitivity C-reactive protein (hsCRP) assay. RESULTS A total of 120 subjects (64.2% women, mean age 59.8±10.2 years) were enrolled at this study. Subjects with lower Med Diet pattern adherence exhibited higher occurrence of metabolic syndrome and all its components and higher HOMA-IR and hsCRP values (P for all <0.0001). Subjects with metabolic syndrome were less likely to consume olive oil (P=0.002) and vegetables (P=0.023). By multivariable analyses, the overall Med Diet score was found to be strongly and inversely associated with the presence of metabolic syndrome [B=-0.066; 95% confidence interval (CI) -0.105 to -0.028; P=0.001], IFG (B=-0.076; 95% CI -0.114 to -0.038; p<0.0001), high HOMA-IR (B=-0.071; 95% CI -0.108 to -0.034; P<0.0001) and high hsCRP (B=-0.082; 95% CI -0.125 to -0.045; P<0.0001). None of specific Med Diet items independently predicted metabolic syndrome, IFG, and high HOMA-IR. Instead, the consumption of white meat over red meat (B=-0.324; 95% CI -0.467 to -0.178; P<0.0001) was found to be inversely associated with increased hsCRP. CONCLUSIONS The inverse associations between adherence to Med Diet and the prevalence of metabolic syndrome and prediabetes may be due more to the effects of the entire dietary pattern rather than to individual food components. Metabolic syndrome-related microinflammation may further be linked to specific Med Diet components.

Depressive symptoms in older people with metabolic syndrome: is there a relationship with inflammation?

To investigate if there is a higher prevalence of depressive symptoms in older people with metabolic syndrome (MetS) compared with those without and whether dedpressive symptoms are independently associated to MetS and its single components and to the inflammatory markers.

Exercise training and music therapy in elderly with depressive syndrome: A pilot study

OBJECTIVE Recent studies have thrown doubt on the true effectiveness of anti-depressants in light and moderate depression. The aim of this study is to evaluate the impact of physical training and music therapy on a sample group of subjects affected by light to moderate depression versus subjects treated with pharmacological therapy only. DESIGN AND SETTING Randomized controlled study. Patients were randomized into two groups. Subjects in the pharmacotherapy group received a therapy with antidepressant drugs; the exercise/music therapy group was assigned to receive physical exercise training combined with listening to music. The effects of interventions were assessed by differences in changes in mood state between the two groups. MAIN OUTCOME MEASURES Medically eligible patients were screened with the Hamilton Anxiety Scale and with the Geriatric Depression Scale. We used plasmatic cytokine dosage as a stress marker. RESULTS We recruited 24 subjects (mean age: 75.5 ± 7.4, 11 M/13 F). In the pharmacotherapy group there was a significant improvement in anxiety only (p<0.05) at 6-months. In the exercise/music therapy was a reduction in anxiety and in depression at 3-months and at 6-months (p<0.05). We noted an average reduction of the level of TNF-a from 57.67 (± 39.37) pg/ml to 35.80 (± 26.18) pg/ml. CONCLUSIONS Our training may potentially play a role in the treatment of subjects with mild to moderate depression. Further research should be carried out to obtain more evidence on effects of physical training and music therapy in depressed subjects.

Role of cardiovascular risk factors (CRF) in the patients with mild cognitive impairment (MCI)

Few therapeutic options are available nowadays to improve the prognosis of patients with Alzheimers disease (AD). There are rather several evidences in literature that controlling vascular risk factors may be an effective intervention for modifying the course of this disease. The aim of our study was to investigate the role of CRF in 50 patients with MCI according to Petersenss criteria, and to evaluate their influence on cognitive and behavioral features of the disease and on the development of dementia. Statistical analysis of the data showed that the 60% of the patients with MCI and CRF developed dementia, while 40% maintained the same cognitive conditions at the end of the study. Only 32% of the subjects without cardiovascular comorbidities developed dementia. The results of the study suggest that CRF play a key role in cognitive decline of patients with MCI. Patients with MCI and CRF showed not only worse cognitive performances, but also behavioral disorders, depression and functional disability. Patients with CRF had higher conversion rate to AD than the other group, with a mean disease-free period 3 months shorter than the control group.

Lipoprotein (a) serum levels in patients with hepatocarcinoma.

Lipoprotein (a) [Lp(a)] is synthesised by liver cells, and patients with liver cirrhosis (LC) show low serum levels of Lp(a) associated with the degree of liver failure. On the contrary, increased serum levels of Lp(a) have been reported in patients with cancer. In this report, the behaviour of Lp(a) serum levels in patients with hepatocarcinoma (HC), a complication of LC, has been evaluated with the aim to study whether HC cells were able to cause an increase of serum concentrations of this lipoprotein when impaired liver protein synthesis is present. We selected eighteen patients affected by LC + HC, eighteen patients matched for sex, age and degree of liver failure with LC only, and eighteen patients with other cancer types. A significant increase of serum levels of Lp(a) was observed in patients affected by LC + HC or other cancer types compared with healthy subjects. Forty-four percent of LC + HC patients showed Lp(a) values more than 70.4 Units/dl, i.e., the upper limit of values observed in patients with LC only. Lp(a) serum concentrations were significantly associated with serum albumin both in LC and in LC + HC but not in other cancer-type patients. Thus, comparing patients with similar serum albumin concentrations, Lp(a) serum levels were significantly higher in patients with LC + HC than in patients with only LC and quite similar to those observed in patients with other cancer types. In conclusion, HC cells, in vivo, seem able to produce a greater amount of Lp(a) despite the reduced liver protein synthesis typical of LC.

Normocaloric low cholesterol diet modulates Th17/Treg balance in patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17-cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates Th17/Treg balance, improving immune system response in CHC patients. This study could pave the way for new treatments of CHC patients, suggesting that change in lifestyle could support the management of these patients, promoting well-being and possibly hindering disease progression. Trial Registration ClinicalTrials.gov NCT02038387

Relationship between lipoprotein(a) levels in serum and some indices of protein synthesis in liver cirrhosis

Recent research has demonstrated that the major site of apolipoprotein(a) synthesis, the characteristic protein of lipoprotein(a) (Lp(a)), is the liver and that patients affected by liver cirrhosis have low serum concentrations of Lp(a). Nevertheless, it is still not clear whether Lp(a) behaviour in these patients is related to reduced hepatic protein synthesis, or to decreased serum lipid levels or to both these conditions. In order to investigate further the behaviour of Lp(a) and, in particular, its relationship with some indices of blood lipids and coagulation, 30 patients affected by liver cirrhosis have been studied. Significantly low serum values of Lp(a) were observed in patients with more severe hepatic injury included in classes B and C according to the Child-Pugh score. Lipoprotein(a) was directly correlated with prothrombin plasma activity and with apolipoprotein B-100 and albumin concentrations in serum. This study confirms low serum levels of Lp(a) in cirrhotic patients and suggests that its decrease could be partly due to impaired liver protein synthesis.

Associations of plasma glucose levels and traits of metabolic syndrome with carotid intima media thickness in nondiabetic elderly subjects: are they mediated by insulin resistance?

BACKGROUND The independent role of insulin resistance (IR) and high fasting blood glucose (FBG) levels within the normal range on vascular diseases is still under debate. This study was designed to explore whether IR, FBG levels, and the traits of metabolic syndrome are associated with increased carotid intima media thickness (IMT), the early marker of subclinical atherosclerosis, independently of each other in nondiabetic elderly subjects. METHODS Blood analytes and anthropometric measurements were obtained. Carotid IMT was measured by ultrasonography; metabolic syndrome was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. IR was assessed through homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS At total of 207 subjects aged 68.2±3.6 years were enrolled. Subjects with increased carotid IMT (50.7%) were older (P=0.001), had a higher prevalence of metabolic syndrome (P<0.0001) and all its traits, impaired fasting glucose (IFG) (P<0.0001), and values of HOMA-IR (P<0.0001) than normal subjects. Increased carotid IMT significantly correlated with metabolic syndrome, its traits, IFG, and HOMA-IR. When multivariable regression models were constructed, central obesity [B=0.392; 95% confidence interval (CI) 0.280-0.505; P<0.0001], high-density lipoprotein cholesterol (HDL-C) (B=-0.007; 95% CI -0.013-0.000; P=0.042], hypertension (B=0.475; 95% CI 0.363-0.587; P<0.0001), and IFG (B=0.230; 95% CI 0.092-0.367; P=0.001) were found to be the independent determinants of increased carotid IMT independently of HOMA-IR, but not FBG (B=0.013; 95% CI 0.000-0.026; P=0.050) and HOMA-IR itself. CONCLUSIONS Our results suggest that hypertension, low HDL-C, and central obesity are independently associated with increased carotid IMT in nondiabetic elderly subjects. These associations seem to be not affected by IR. The associations of FBG levels within the normal range and IR with carotid IMT should be investigated further.

Executive dysfunction assessed by Clock-Drawing Test in older non-demented subjects with metabolic syndrome is not mediated by white matter lesions

Metabolic syndrome (MetS) has been associated with greater occurrence of white matter hyperintensities (WMH). It remains uncertain whether MetS as a construct is associated with poorer cognitive performances. This study explores whether MetS is associated with poorer performances in global and domain‐specific cognitive tests in older non‐demented subjects independently of its individual components, WMH severity and other variables.

Metabolic Syndrome, Executive Dysfunction, and Late‐Onset Depression: Just a Matter of White Matter?

We are grateful to the participants for their cooperation. Conflict of Interest: The study was financially supported by the Angers University Hospital. Dr. Annweiler has served as an unpaid consultant for Ipsen Pharma company and serves as an associate editor for G eriatrie, Psychologie et Neuropsychiatrie du Vieillissement and for the Journal of Alzheimer’s Disease. He has no relevant financial interest in this manuscript. Prof. Beauchet has served as an unpaid consultant for Ipsen Pharma company and serves as an associate editor for G eriatrie, Psychologie et Neuropsychiatrie du Vieillissement. He has no relevant financial interest in this manuscript. Author Contributions: Beauchet had full access to the data in the study. Study concept and design: Noublanche, Decavel, Beauchet. Acquisition of data: Noublanche, Simon. Analysis and interpretation of data: Noublanche, Simon, Annweiler, Beauchet. Drafting of the manuscript: Noublanche, Beauchet, Annweiler. Critical revision of the manuscript for important intellectual content: Simon, Decavel, Lefort. Obtained funding: Noublanche, Decavel, Lefort. Statistical expertise: Beauchet. Administrative, technical, or material support: Noublanche, Decavel, Lefort. Study supervision: Beauchet, Decavel. Sponsor’s Role The sponsors had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or in preparation, review, or approval of the manuscript.