Nonalcoholic fatty liver disease (NAFLD) is consistently associated with features of the metabolic syndrome, a condition carrying a high risk of cardiovascular events. We measured the vasodilatory response of the brachial artery in response to ischemia (a test of endothelial function) (FMV) as well as cardiovascular risk profile in 52 NAFLD cases and 28 age-and sex-matched controls. The 10-year risk of coronary events was calculated according to the Framingham equation and the scores derived from the PROCAM study and NCEP-ATPIII proposals. FMV was 6.33% ؎ 5.93% in NAFLD versus 12.22% ؎ 5.05% in controls (P < .0001), and higher in pure fatty liver (9.93%) compared with nonalcoholic steatohepatitis (4.94%) (P ‫؍‬ .010). No differences were observed in flow-independent vasodilation (response to sublingual nitroglycerin). Percent FMV was negatively associated with insulin resistance (homeostasis model assessment) in the whole population (r ‫؍‬ ؊0.243; P ‫؍‬ .030). In logistic regression analysis, NAFLD was associated with a percent FMV in the lower tertile (OR, 6.7; 95% CI, 1.26-36.1), after adjustment for age, sex, body mass index, and insulin resistance. Among NAFLD patients, low FMV was associated with nonalcoholic steatohepatitis (adjusted OR, 6.8; 95% CI, 1.2-40.2). The 10-year probability of cardiovascular events was moderately increased in NAFLD, and particularly in nonalcoholic steatohepatitis. In conclusion, our study provides evidence of endothelial dysfunction and increased risk of cardiovascular events in NAFLD. The risk of advanced liver disease is well recognized in NAFLD patients, but the large majority of cases might experience cardiovascular disease in the long term, indirectly limiting the burden of liver failure. (HEPATOLOGY 2005;42:473-480.)

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. NAFLD is considered the hepatic component of the metabolic syndrome and insulin resistance represents its pathophysiological hallmark. Insulin resistance in NAFLD is characterized by reduced whole-body, hepatic, and adipose tissue insulin sensitivity. The mechanism(s) underlying the accumulation of fat in the liver may include excess dietary fat, increased delivery of free fatty acids to the liver, inadequate fatty acid oxidation, and increased de novo lipogenesis. Liver fat is highly correlated with all the components of the metabolic syndrome, independent of obesity, and NAFLD may increase the risk of type 2 diabetes and atherosclerosis. Overproduction of glucose, very low-density lipoproteins, C-reactive protein and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease. The reason(s) why some patients will develop NASH are poorly understood. Circulating free fatty acids may be cytotoxic by inducing lipid peroxidation and hepatocyte apoptosis. Insulin resistance is often associated with chronic low-grade inflammation, and numerous mediators released from immune cells and adipocytes may contribute liver damage and liver disease progression. Understanding the molecular mediators of liver injury would promote the development of mechanism-based therapeutic interventions. This article briefly summarizes the recent advances in our understanding of the relationship between NAFLD/NASH, insulin resistance and the metabolic syndrome.

Liver disease of metabolic origin, associated with obesity, is now recognized as the most prevalent liver disease in Western countries. Strategies are needed to approach obesity-associated liver disease by behavior programs, motivating people to adopt a healthier lifestyle. Such programs should be coupled with public policies at a societal level to obtain the maximum effects in lifestyle changes.

IntroductionThe COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 (‘lockdown’), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors.Research design and methodsWe enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13–17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires.ResultsIn children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)<54 mg/dL (TBR2) (p=0.029) were detected after lockdown. CGM metrics were comparable in teenagers before and during lockdown. After lockdown, adults improved significantly time in range (TIR) 70–180 mg/dL (p<0.001) and remaining metrics, except percent coefficient of variation and TBR2. In adults, considering the changes in SDglu and TIR occurred before and during lockdown, we identified a group with improved TIR and SDglu who performed more physical activity, one with improved glucose variability who was younger than the other patients, and one with worsened glucose variability who showed higher perceived stress than others.ConclusionIn patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.

Introduction The metabolic syndrome (MetS) is a multifactorial disease characterized by the co-occurrence of impaired glucose tolerance/diabetes, central obesity, high levels of triglycerides, low levels of high-density lipoprotein, and hypertension. Its prevalence is higher in menopausal women. We, and others, have recently shown that female sexual dysfunction (FSD) affects menopausal women. Whether the presence of MetS may be linked to a higher risk of FSD in menopausal women is unknown. Aims The aims of our study were: (i) to evaluate the prevalence of FSD in women with MetS (based on National Cholesterol Education program-Adult Treatment Panel III 2009 criteria) in comparison with healthy controls and (ii) to evaluate the influence of singular components of MetS on female sexual function. Methods The Female Sexual Function Index (FSFI) questionnaire, the Female Sexual Distress Scale (FSDS), and The Middlesex Hospital Questionnaire were administered to 103 postmenopausal women with MetS and 105 healthy postmenopausal controls (HC). Female sexuality was defined as dysfunctional when FSFI score was &lt;23 and FSDS was &gt;15. Main Outcome Measures FSFI and FSDS were completed by women with and without MetS. Results The prevalence of women with sexual dysfunction was higher in MetS women than HC (39/103 [37.9%] vs. 20/105 [19%], P = 0.003). The prevalence of both pathological scores in every FSFI domain and FSDS score was higher in MetS women than HC. The logistic regression, considering age and the length of relationship as a common starting point, shows that higher levels of triglycerides are linked to a higher risk of presenting FSD (odds ratio = 2.007 95% confidence interval [1.033–3.901]) in the whole population. Conclusions Our preliminary results suggest that prevalence of FSD is higher in women with MetS in comparison with healthy controls. Higher levels of triglycerides are linked to a higher risk of presenting FSD.