Critical evaluation of the questionnaires assessing adherence to the Mediterranean diet that are based on servings.

BACKGROUND AND AIMS: The Mediterranean Diet (MD) is characterized by a high intake of vegetables, fruit, legumes, nuts, and olive oil, and moderate fish, dairy, and wine intake. A high adherence to MD has been associated with numerous health benefits, including reduced risk of chronic diseases such as cardiovascular disease, cancer, and type 2 diabetes. The clinical assessment of MD adherence is complicated by the absence of a univocally accepted tool and by the abundance of questionnaires developed to determine adherence, whose reliability and validity is uncertain. In this inter-associative document, we critically evaluated servings-based questionnaires for the assessment of MD adherence, aiming to identify the most valuable tool for the use in clinical practice. METHODS AND RESULTS: For each questionnaire, we analyzed the structure, evidence on health-related outcomes and agreement with the recommendations of MD. We found that most questionnaires do not accurately reflect the principles of MD in terms of the food groups and their optimal consumption frequency. Additionally, the comparison of questionnaires revealed low agreement and some concerns with regard to the scoring assumptions. CONCLUSIONS: Among the available questionnaires, we suggest the use of the 15-Items Pyramid based Mediterranean Diet Score (PyrMDS), which is the one with fewer flaws and a strong supporting body of theoretical and scientific evidence. The use of the PyrMDS may facilitate the assessment of MD adherence in clinical practice, which is instrumental in reducing the risk of non-communicable chronic diseases.

Stress Hyperglycemia and Complications Following Traumatic Injuries in Individuals With/Without Diabetes: The Case of Orthopedic Surgery.

PURPOSE: Hyperglycemia in trauma patients may stem from metabolic response to stress, both in the presence and the absence of underlying diabetes. We aimed to test the association of stress hyperglycemia with risks of adverse events subjects undergoing orthopedic surgery. PATIENTS AND METHODS: In a prospective observational study, we enrolled 202 consecutive patients with hyperglycemia at hospital admission for trauma injuries requiring orthopedic surgery. Based on history, diabetes was present in 183, and 13 more were defined as unknown diabetes on the basis of HbA1c ≥48mmol/mol. Stress hyperglycemia was defined in subjects with/without diabetes by a stress hyperglycemia ratio (SHR) >1.14, calculated as admission glucose/average glucose, estimated from glycosylated hemoglobin. Logistic regression analysis was used to calculate the risk of post-surgery adverse events associated with different states of hyperglycemia, after correction for demographic and clinical confounders. RESULTS: Stress hyperglycemia was diagnosed, either as superimposed to diabetes (54/196 cases, 27.6%) as well as in the 6 cases without diabetes. At least one complication was recorded in 68 cases (33.7%), the most common being systemic infection (22.8% of cases). In the total cohort, stress hyperglycemia, irrespective of the presence of diabetes, increased the risk of adverse events (any events, odds ratio [OR], 4.43; 95% confidence interval [CI], 2.11-9.30), cardiovascular events (OR, 7.09; 95% CI, 2.47-19.91), systemic infections (OR, 4.21; 95% CI, 1.97-9.03) and other adverse events (OR, 6.30; 95% CI, 1.41-28.03), after adjustment for confounders; hospital stay was much longer. The same was true when the analysis was limited to the diabetes cohort or by comparing pure stress hyperglycemia vs diabetes without stress hyperglycemia. CONCLUSION: The study highlights the importance of stress hyperglycemia for adverse events in the setting of orthopedic surgery following trauma injuries. This condition requires stricter management, considering the much longer length of hospital stay and higher costs.

Combination of GLP-1 receptor agonists and behavioural treatment in type 2 diabetes elicits synergistic effects on body weight: A retrospective cohort study.

AIMS: Intensification of type 2 diabetes (T2DM) treatment with GLP-1 receptor agonists (GLP-1RAs) promotes weight loss. We aimed to determine the synergistic effect of behavioural programmes on body weight on top of GLP-1RA treatment. MATERIALS AND METHODS: We retrospectively analysed the time course of 328 individuals with T2DM starting GLP-1RA treatment because of insufficient metabolic control. In 29, a structured programme of elementary nutritional counselling was also implemented (elementary nutritional education [ENE]-5 group sessions), whereas 53 entered a programme of cognitive-behavioural treatment (CBT-12 group sessions). Both programmes were completed within 6 months of switching to GLP-1RAs. Data of body weight and metabolic control were followed up to 2 years as part of regular follow-up. Weight loss targets (≥10% and ≥5%) and metabolic target (HbA1c < 7%) were analysed by Cox regression model in comparison with standard care (SC, N = 244). RESULTS: Body weight remarkably decreased following both behavioural programmes, with significant differences compared with SC at 2 years (CBT, 8.5 ± 5.9% vs 6.3 ± 6.9 in ENE and only 3.1 ± 5.7 in SC; P < 0.001 and P = 0.045 vs CBT and ENE, respectively). The 10% weight loss was achieved and maintained in approximately 30% of cases during follow-up, and an additional 35% of cases lost between 5% and 10%. Data were consistent between behavioural programmes, after adjustment for confounders, including initial body weight (logreg Mantel-Cox: ENE vs SC, P < 0.01; CBT vs SC, P < 0.001). No differences in metabolic control were detected between groups. CONCLUSIONS: Initiation of GLP-1RA treatment provides an opportunity for addressing patients' needs of weight control. By producing initial weight loss, patients' motivation and self-efficacy are expected to increase and adherence to long-term lifestyle changes might be more easily attained.

An internet-based approach for lifestyle changes in patients with NAFLD: Two-year effects on weight loss and surrogate markers.

BACKGROUND & AIMS: Interventions aimed at lifestyle changes are pivotal for the treatment of non-alcoholic fatty liver disease (NAFLD), and web-based programs might help remove barriers in both patients and therapists. METHODS: In the period 2010-15, 716 consecutive NAFLD cases (mean age, 52; type 2 diabetes, 33%) were treated in our Department with structured programs. The usual protocol included motivational interviewing and a group-based intervention (GBI), chaired by physicians, dietitians and psychologists (five weekly meetings, n = 438). Individuals who could not attend GBI entered a web-based intervention (WBI, n = 278) derived from GBI, with interactive games, learning tests, motivational tests, and mail contacts with the center. The primary outcome was weight loss ≥10%; secondary outcomes were alanine aminotransferase within normal limits, changes in lifestyle, weight, alanine aminotransferase, and surrogate markers of steatosis and fibrosis. RESULTS: GBI and WBI cohorts had similar body mass index (mean, 33 kg/m2), with more males (67% vs. 45%), younger age, higher education, and more physical activity in the WBI group. The two-year attrition rate was higher in the WBI group. Healthy lifestyle changes were observed in both groups and body mass index decreased by almost two points;the 10% weight target was reached in 20% of WBI cases vs. 15% in GBI (not significant). In logistic regression analysis, after adjustment for confounders and attrition rates, WBI was not associated with a reduction of patients reaching short- and long-term 10% weight targets. Liver enzymes decreased in both groups, and normalized more frequently in WBI. Fatty liver index was reduced, whereas fibrosis remained stable (NAFLD fibrosis score) or similarly decreased (Fib-4). CONCLUSION: WBI is not less effective than common lifestyle programs, as measured by significant clinical outcomes associated with improved histological outcomes in NAFLD. eHealth programs may effectively contribute to NAFLD control. LAY SUMMARY: In patients with non-alcoholic fatty liver disease, participation in structured lifestyle programs may be jeopardized by job and time constraints. A web-based intervention may be better suited for young, busy patients, and for those living far from liver units. The study shows that, following a structured motivational approach, a web-based, interactive intervention coupled with six-month face-to-face meetings is not inferior to a standard group-based intervention with respect to weight loss, adherence to healthy diet and habitual physical activity, normalization of liver enzymes, and stable surrogate markers of fibrosis.

Pharmacotherapy of type 2 diabetes in patients with chronic liver disease: focus on nonalcoholic fatty liver disease.

INTRODUCTION: Pharmacotherapy used to treat type 2 diabetes mellitus (T2DM) is facing a paradigm shift in clinical practice with recent cardiovascular (CV) outcome trials having a substantial impact on drug prescription with treatment having a more tailored approach. In patients with T2DM, the issue of chronic liver disease is multifaceted. However, a clinical evidence is emerging on the beneficial effect of antidiabetic medications on nonalcoholic fatty liver disease (NAFLD). AREAS COVERED: The authors provide a synopsis on the current and upcoming pharmacotherapy for NAFLD, including the challenges with their development, focusing on drugs for T2DM. Clinical data on the potential benefits and safety issues are assessed with the aim of proposing an individualized algorithm for patient management. Both MEDLINE and ClinicalTrials.Gov are used to derive the relevant information. EXPERT OPINION: Considering the pivotal role of insulin resistance in NAFLD, insulin sensitizers should be the treatment of choice. Accordingly, pioglitazone is the only drug with a significant effect on liver fibrosis, the driver of disease progression and long-term outcome. Among new glucose-lowering drugs, glucagon-like-peptide 1 receptor agonists or sodium-glucose cotransporter type 2 inhibitors have shown positive effects in phase II studies and are qualifying as potential candidates for NAFLD treatment in diabetes.

Trend over time in hepatic fibrosis score in a cohort of type 2 diabetes patients.

AIMS: The prevalence and progression of hepatic fibrosis and its correlated factors in type 2 diabetes (T2DM) are poorly known. We aimed to define the percentage of T2DM patients who progress to fibrosis and the factors associated with disease progression. METHODS: Data from the electronic health records of 1527 patients with diagnosed T2DM and nonalcoholic fatty liver disease (NAFLD), as diagnosed by the Fatty Liver Index, were extracted from the AMD Annals database, which collects data from the Italian network of diabetes clinics. For the main analysis, we evaluated variables associated with Fibrosis 4 [FIB-4] score at baseline and at 3-year follow-up to determine their role in predicting FIB-4 at 3 years and the risk of hepatic fibrosis in T2DM. RESULTS: High-risk of advanced fibrosis was detected in 13.1% of patients at baseline and in 18.1% at 3 years, LDL cholesterol, and body-mass index, correlated negatively with baseline FIB-4 scores, whereas gamma glutamil transerasi correlated positively . The FIB-4 score at 3 years was associated with lower values of baseline renal function, LDL, and BMI; however, the baseline FIB-4 score was the strongest predictor for the FIB-4 score at 3 years. CONCLUSIONS: The prevalence of and progression to hepatic fibrosis within 3 years in patients with T2DM is not negligible. Patients with a higher likelihood of liver scarring differ from those with hepatic steatosis. Differently from NAFLD, the FIB-4 score is inversely correlated with insulin resistance and appears to increase independent of classic metabolic factors.

Which treatment for type 2 diabetes associated with non-alcoholic fatty liver disease?

Type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in the community, and share common pathogenic mechanisms. There is also evidence that T2DM may be favored by hepatic fat accumulation; in turn the presence of T2DM is a risk factor for liver disease progression. The treatment of T2DM has considerably changed in the past few years; new drug classes, promoting glucose-lowering through mechanisms different from classical insulin-sensitizing or insulin-secreting action, have been added to continuing lifestyle intervention. Metformin and pioglitazone may be safely used in the presence of liver fat, whereas sulfonylureas and insulin itself have been associated with NAFLD progression and adverse outcome. Drugs acting on the incretin axis and on Na-glucose co-transport at renal tubular level offer new hopes for a tailored treatment able to reduce the burden of hepatic triglyceride accumulation and liver disease progression.

Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction.

BACKGROUND: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). KEY MESSAGES: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. CONCLUSIONS: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.

The role of medications for the management of patients with NAFLD.

The article is intended to provide an overview of the strengths and limits of controlled trials of pharmacologic treatment of nonalcoholic fatty liver disease. No drug has so far been approved, although validated on histologic outcomes. Several new drugs are under scrutiny, acting with different mechanisms along the chain of events from fatty liver to fibrosis, cirrhosis, and hepatocellular carcinoma. The article investigates which drug, if any, should be preferred for a tailored intervention in individual patients, according to age, comorbidities, and disease severity, and if treatment should be continued lifelong, to prevent disease progression and long-term occurrence of cirrhosis.

A psychological support program for individuals with Type 1 diabetes.

We aimed to test the effects of a psychological support program on the psychological distress, mood, and quality of life of well-educated individuals with type 1 diabetes. A newly developed support program was offered to 60 patients with type 1 diabetes on intensive insulin treatment, previously enrolled in group-care educational programs. Thirty-three subjects participated (experimental group, in groups of 8-12 subjects); 22, who postponed their entry, were used as controls. The program consisted of 7 weekly work sessions of 2 hours chaired by a psychologist and covered aspects of daily living with diabetes using role-playing, metaplan, and problem solving. At baseline and approximately 6 months later, all participants completed a battery of questionnaires, and the differences between the experimental and the control group were analyzed by repeated-measurements ANOVA. In response to the psychological support program, subjects in the experimental group reduced their depressive mood (Beck Depression Inventory and depression scales of the Psychological Well-Being Index) and anxiety (Self-rating Anxiety Scale), improved disease-specific quality of life (Symptom and Well-Being scales of the Well-Being Enquiry for Diabetes), increased their internal and decreased their external locus of control. These changes were accompanied by a 0.3% decrease in glycosylated hemoglobin, whereas no significant changes were observed in the control group (ANOVA, P = 0.032). These results underline the importance of psychological aspects in individuals with type 1 diabetes; treating the psychological aspects related to the disease may be as important as medical control in order to improve living with diabetes.

Insulin resistance: mechanism and implications for carcinogenesis and hepatocellular carcinoma in NASH.

INTRODUCTION: The effects of insulin resistance in human diseases are of paramount importance. Since the original proposal by the WHO indicating insulin resistance as the common substrate of the metabolic syndrome, large data are now available on its significance in cardiovascular diseases, nonalcoholic fatty liver disease and cancer risk. MATERIALS AND METHODS: We reviewed the evidence linking hyperinsulinemia to insulin resistance and ultimately to increased cancer risk. Insulin resistance, by reducing substrate flux along the PI3-K pathway, is followed by compensatory hyperinsulinemia, considered a potential stimulus for cancerogenesis along the MAP-K pathway. Adaptive mechanisms of fat storage, promoted by insulin resistance, chronically maintained in an obesiogenic environment, may lead to oxidative stress and inflammation and modify the immune responses, further increasing the carcinogenic potential. The increased cancer risk associated with obesity, type 2 diabetes and nonalcoholic fatty liver may thus be fueled by hyperinsulinemia. Insulin secretagogs and insulin treatment, by raising circulating insulin levels, further increase cancer risk, whereas insulin sensitizers are associated with decreased cancer risk (all sites) and specifically decrease hepatocellular carcinoma. Likewise, drugs related to the incretin system, which are weight neutral or even reduce whole-body and hepatic fat, improve insulin sensitivity and potentially reduce the cancer risk. CONCLUSION: New diabetes treatments might thus help decrease the future burden of diabetes-associated cancer and particularly of hepatocellular carcinoma.

Effects of cognitive-behavioral treatment for weight loss in family members.

The possibility that lifestyle changes may be shared by the family members of subjects with obesity attending cognitive-behavioral treatment (CBT) for weight loss has been scarcely evaluated. The purpose of this study was to measure the changes in body weight, lifestyle habits, and stage of change toward physical activity in the family members of 149 subjects with overweight/obesity enrolled into a weekly group CBT for weight management in the years 2007-2008. 230 adult (aged >18 years) family members (129 spouses, 72 children (43 female, 29 male), 29 with a different family relationship) completed a self-administered questionnaire at baseline and soon after the end of the completion of their relatives' program (approximately 6 months later). The questionnaire consisted of qualitative information regarding food choices, estimation of energy and food intake, self-report of height and weight, and motivation toward physical activity. At baseline, self-reported body mass index was normal in 115 cases, in the range 25 to 29.9 in 80 and ≥30 in 35. Following CBT of their relatives, the family members significantly reduced their average daily energy intake (-232 kcal/day; P<0.001) and the reported body weight decreased on average by 1 kg (P=0.001). The analysis of food choices revealed a reduced average daily amount of energy from dressings (-40 kcal, P<0.001), main courses with cheese or fat meat (-24 kcal, P=0.002), refined carbohydrates (-16 kcal, P<0.001), bread (-58 kcal, P<0.001), breakfast biscuits (-23 kcal, P=0.005), chocolate (-7 kcal, P=0.024), and nonalcoholic beverages (fruit juices and carbonated drinks; -10 kcal; P=0.013), whereas fruit consumption was increased (+10 kcal; P=0.023). There was also a shift in the stage of change toward exercising. Body mass index changes of family members and CBT subjects were significantly correlated, mainly within spouses. In conclusion, CBT for weight loss positively influences the lifestyle habits of family members of participants, reducing energy intake and promoting a more favorable attitude toward physical activity.

HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas.

Viral infections and the metabolic syndrome may coexist in several individuals, due to the large prevalence of obesity and type 2 diabetes mellitus (T2DM). Antiviral therapy has changed the natural history of chronic viral hepatitis, but viral infection may remain undiagnosed in the absence of systematic screening. We determined the prevalence of HBV and/or HCV infection in an Italian cohort with T2DM (859 consecutive patients, 413 females) in three Italian centers: Turin, Bologna, and Naples. Screening for viral disease was coupled with the determination of parameters of metabolic syndrome. Fourteen patients were HBsAg-positive, 51 anti-HCV with a prevalence of genotype-1 infection in 58% of cases. Thirty cases had newly diagnosed viral markers, only one-third had already-diagnosed liver disease, 16 were being followed-up by a Liver Unit, and 9 cases had received antiviral treatment. Patients with viral markers had higher liver enzyme levels in comparison with virus-negative patients (P < 0.0001), whereas the prevalence of the metabolic syndrome was similar in the 2 groups. A positive correlation between BMI and alanine aminostransferase levels was only present in virus-negative cases, where the probability of enzyme levels above the upper limit of normal increased by 5% for unit of increase in BMI (OR: 1.05; 95% CI: 1.003-1.100, P = 0.037). In conclusion, the prevalence of HBV and HCV is non-negligible in patients with T2DM, but these cases may long remain undiagnosed. Elevated liver enzymes might be frequently disregarded in diabetes Units and ascribed to metabolic syndrome, thus excluding T2DM patients from specific disease-modifying antiviral treatment for hepatitis.