Sex-driven factors associated with anxiety and depression in autoimmune diabetes.

AIM: To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy), to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4 months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled). RESULTS: Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31-0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1 year increase, 95% CI 0.92-1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1 mmol/mol increase, 95% CI 1.03-1.13; p = 0.002). CONCLUSION: Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females.

Sleep quality and sex-related factors in adult patients with immune-mediated diabetes: a large cross-sectional study.

AIM: To analyze sleep quality and its relationships with clinical and biochemical features in a large cohort of adults with autoimmune diabetes. METHODS: We administered to 553 patients with autoimmune diabetes the questionnaires: Pittsburgh Sleep Quality Index (PSQI), diabetes distress scale, diabetes-related quality of life and diabetes treatment satisfaction questionnaire. We excluded patients with missing HbA1c ± 4 months from PSQI administration or incorrect PSQI compilation (n = 110). RESULTS: Altered sleep quality was recorded in 142/443 subjects (32%), insufficient total sleep time in 177/443 (40%). The altered sleep quality group had higher HbA1c (median 56 mmol/mol [interquartile range-IQR 49-62] vs 59 [IQR 52-68]; P < 0.001), higher average HbA1c in the previous 36 months (59 mmol/mol [IQR 54-68] vs 56 [IQR 51-62]; P < 0.001), and more individuals with HbA1c > 53 mmol/mol (74.6% vs 62.8%; P = 0.014). Diabetes duration (P = 0.63), type of insulin delivery (P = 0.48) and glucose monitoring (P = 0.35) were uninfluential. Patients with altered sleep quality showed higher prevalence of autoimmune (42 vs 28%; P = 0.005) and mental diseases (12 vs 4%; P = 0.002); there were greater emotional distress, and lower quality of life and treatment satisfaction (P < 0.001 for all), irrespective of sex. Men with altered sleep quality had higher HbA1c and prevalence of autoimmune diseases. Women showed greater prevalence of psychiatric disorders. Average HbA1c of the previous 36 months, autoimmune or psychiatric disorders were independent predictive factors for altered sleep quality. CONCLUSION: One-third of the patients with autoimmune diabetes showed altered sleep quality, which associates with worse glycemic control, and autoimmune and mental disorders, with sex-specific differences.

Tackling diabetes as a team: co-designing healthcare interventions to engage couples living with type 1 diabetes.

AIMS: Couples living with Type 1 diabetes: co-designing interventions to support them. METHODS: This is a qualitative study comprising two phases. Phase I represents the exploratory phase, consisting of semi-structured interviews with persons with Type 1 diabetes (N = 16) and partners (N = 6). In the second phase, co-design principles guided workshops with healthcare professionals, persons with Type 1 diabetes, and partners (N = 7) to facilitate discussion of the key themes identified and solutions to engage couples living with Type 1 diabetes in diabetes care. RESULT: The key themes identified from phase I as priorities to target in future interventions were: (i) Emotional impact of diabetes and (ii) Partners' involvement. Priority (i) captures the impact the emotional burden of diabetes management produces within couples' relationship. Priority (ii) captures the request from partners to be more involved in diabetes management. Characteristics of the interventions suggested during the co-design phase II focused on engaging patients and partners via a counseling point in healthcare settings and tailored help for couples' psychological support needs. CONCLUSIONS: Couples value pro-active intervention and support from their diabetes team or primary care for both the partners to live well with Type 1 diabetes.

Association between alterations of corneal sub-basal nerve plexus analyzed with in vivo confocal microscopy and long-term glycemic variability.

PURPOSE: The effect of long-term glycemic variability upon corneal sub-basal nerve plexus (CSNP) morphology analyzed by in vivo confocal microscopy (IVCM) has been poorly investigated in the setting of type 1 diabetes mellitus (T1DM). Our purpose was to analyze the association between morphometric parameters of CSNP and new markers of glycemic variability in a population of patients with T1DM. METHODS: Forty patients with T1DM underwent: assessment of diabetic neuropathy (DN); analysis of subcutaneous advanced glycated end-products; IVCM scans of CSNP. The fully automated software ACCMetrics was employed to analyze IVCM images and calculate seven corneal nerve parameters. Data of diabetes duration, mean and standard deviation (SD) of either last-year and all-time glycated hemoglobin (HbA1C) were retrieved. RESULTS: Diabetes duration and all-time SD of HbA1C were independently associated with CNFD (R = -0.26, p = 0.01; R = -0.27, p = 0.047 respectively), CNFL (R = -0.12; p = 0.01; R = -0.17, p = 0.01 respectively) and CNFrD (R = -0.001, p = 0.009; R = -0.002, p = 0.007 respectively). The analysis of the association among IVCM parameters and specific subtypes of DN showed that altered cold sensitivity was independently associated with CNFD (B = -0.24, p = 0.01), CNFL (B = -0.46, p = 0.01) and CNFrD (B = -28.65, p = 0.03). CONCLUSIONS: All-time SD of HbA1C and disease duration were found to be independent predictors of damage to CSNP in patients with T1DM.

Comparison of the effects of lockdown due to COVID-19 on glucose patterns among children, adolescents, and adults with type 1 diabetes: CGM study.

INTRODUCTION: The 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 METHODS: We 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. RESULTS: In 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. CONCLUSION: In 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.

Impaired Lipid Profile is a Risk Factor for the Development of Sexual Dysfunction in Women.

INTRODUCTION: Dyslipidemia is a common risk factor for cardiovascular disease which may contribute to sexual dysfunction in women. AIMS: To assess the impact of dyslipidemia compared with other metabolic alterations on female sexual function. METHODS: In total, 466 women were enrolled in the study, of which 256 were postmenopausal. Dyslipidemia was defined based on high-density lipoprotein, low-density lipoprotein, or triglycerides levels. Women completed the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the Middlesex Hospital Questionnaire (MHQ). Biochemical and anthropometric measurements were performed and the Framingham risk score (FRS) was calculated for each subject. MAIN OUTCOME MEASUREMENTS: FSFI, FSDS, and MHQ scores, prevalence of FSD and FRS. RESULTS: Median age of the population enrolled was 51.5 (range 42.0-58.0) years. The overall prevalence of FSD, according to FSFI and FSDS scores, was 24%. A significantly higher prevalence of FSFI (P = .001) and FSDS (P = .006) pathological scores were found in women with dyslipidemia compared with the control group. The prevalence of FSD was significantly higher in dyslipidemic women (P = .001). Women with dyslipidemia had significantly higher total scores in areas of depression, somatization, and obsession in the MHQ questionnaire compared with control women. Multivariate analysis showed that dyslipidemia (OR:1.7, CI 1.1-2.9, P = .037), postmenopausal status (OR:2.7, CI 1.5-4.7, P = .001), higher education (OR:0.6; CI 0.3-0.9, P = .038), and somatization (OR:1.7, CI 1.0-2.8, P = .045) were independently associated with FSD. The FRS was higher in dyslipidemic women (P = .001) and in those with FSD (P = .001), being associated with an almost doubled risk of developing FSD. CONCLUSION: Our results indicate that dyslipidemia is an independent risk factor for FSD irrespective of postmenopausal status. Also, psychopathological alterations such as somatization are strongly associated with sexual dysfunction. The direct correlation between FSFI score and FRS suggest the importance of cardiovascular integrity in female sexual health.

Physical activity support or weight loss counseling for nonalcoholic fatty liver disease?

AIM: To determine the clinical effectiveness of intense psychological support to physical activity (PA) in nonalcoholic fatty liver disease (NAFLD), compared with cognitive-behavioral treatment (CBT). METHODS: Twenty-two NAFLD cases received support to exercise, tailored to their motivational needs (PA group). The effects on body weight, physical fitness [6-min walk test, VO2max and the PA-rating (PA-R) questionnaire] and body fat (fatty liver indices and visceral adiposity index) were compared with data obtained in 44 NAFLD subjects enrolled in a CBT program for weight loss, after adjustment for propensity score, calculated on baseline data. Measurements were performed at baseline, at 4-mo and one-year follow-up. Changes in anthropometric, biochemical and PA parameters were tested by repeated measurement ANOVA. Outcome results were tested by logistic regression analysis. RESULTS: At the end of the intensive program, BMI was less significantly reduced in the PA group (-1.09 ± 1.68 kg/m(2) vs -2.04 ± 1.42 kg/m(2) in the CBT group, P = 0.019) and the difference was maintained at 1-year follow-up (-0.73 ± 1.63 vs -1.95 ± 1.88, P = 0.012) (ANOVA, P = 0.005). PA-R was similar at baseline, when only 14% of cases in PA and 36% in CBT (P = 0.120) recorded values ≥ 3. At 4 mo, a PA-R ≥ 3 was registered in 91% of PA and 46% of CBT, respectively (P < 0.001) and PA-R ≥ 5 (up to 3 h/wk of moderate-to-heavy intensity physical activity) was registered in 41% of PA and only 9% of CBT group (P < 0.007). The 6-min walk test increased by 139 ± 26 m in PA and by only 43 ± 38 m in CBT (P < 0.001) and VO2max by 8.2 ± 3.8 mL/kg per minute and 3.3 ± 2.7 mL/kg per minute, respectively (P < 0.002). After adjustment for propensity, weight loss > 7% was significantly associated with CBT group at one year (OR = 6.21; 95%CI: 1.23-31.30), whereas PA-R > 3 was associated with PA group (10.31; 2.02-52.63). Liver enzymes decreased to values within normal limits in 36% of PA cases and 61% of CBT (P < 0.070). Estimated liver fat (Kotronen index) fell below the fatty liver threshold in 36% of PA and 34% and CBT cases at one-year (not different). Also the fatty liver index and the visceral adiposity index improved to a similar extent. CONCLUSION: Intensive psychological counseling for PA produces hepatic effects not different from standard CBT, improving physical fitness and liver fat independent of weight loss. Strategies promoting exercise are worth and effective in motivated patients, particularly in lean NAFLD patients where large weight loss cannot be systematically pursued.

Sexuality and psychopathological aspects in premenopausal women with metabolic syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that have been suggested to impact female sexual function. AIMS: This study aims to assess the prevalence of female sexual dysfunction (FSD) in premenopausal women with MetS compared with healthy controls (HC). Psychopathological aspects and the relationship to FSD were also evaluated in both groups. METHODS: Two hundred four premenopausal women, of whom 98 had diagnosis of MetS, were asked to complete the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the Middlesex Hospital Questionnaire (MHQ). Routine laboratory tests and anthropometric measurements were routinely performed. MAIN OUTCOME MEASURES: FSFI and FSDS questionnaires, prevalence of FSD, and MHQ scores. RESULTS: In the MetS group compared with the HC group, we found: a lower global FSFI score (P=0.005), higher prevalence of pathological scores compared with HC group, and lower scores in the desire, arousal, lubrication, and orgasm domains. An inverse correlation between the FSFI score and the number of risk factors for MetS was detected. MetS women reported significantly higher total scores in the somatization and depression domains when compared with the HC group. The logistic regression showed that high triglycerides (odds ratio [OR] 3.097; 95% confidence interval [CI] 1.272-7.542; P=0.026) and somatization (OR 7.068; CI 95% 2.291-21.812; P=0.001) are independently associated with FSD in premenopausal women. CONCLUSIONS: Our results indicate a higher prevalence of sexual dysfunction in MetS women. A number of risk factors for MetS are positively associated with FSD and higher triglycerides seem to be the strongest predictors of sexual dysfunction. Psychopathological dimensions such as somatization are strongly associated with sexual dysfunction.

Preliminary study about the possible glycemic clinical advantage in using a fixed combination of Berberis aristata and Silybum marianum standardized extracts versus only Berberis aristata in patients with type 2 diabetes.

BACKGROUND: Berberine is an isoquinoline alkaloid widely used to improve the glucidic and lipidic profiles of patients with hypercholesterolemia, metabolic syndrome, and type 2 diabetes. The limitation of berberine seems to be its poor oral bioavailability, which is affected by the presence, in enterocytes, of P-glycoprotein - an active adenosine triphosphate (ATP)-consuming efflux protein that extrudes berberine into the intestinal lumen, thus limiting its absorption. According to some authors, silymarin, derived from Silybum marianum, could be considered a P-glycoprotein antagonist. AIM: The study aimed to evaluate the role played by a possible P-glycoprotein antagonist (silymarin), when added to a product containing Berberis aristata extract, in terms of benefits to patients with type 2 diabetes. METHODS: The study enrolled 69 patients with type 2 diabetes in suboptimal glycemic control who were treated with diet, hypoglycemic drugs, and in cases of concomitant alterations of the lipid profile, hypolipidemic agents. The patients received an add-on therapy consisting of either a standardized extract of Berberis aristata (titrated in 85% berberine) corresponding to 1,000 mg/day of berberine, or Berberol®, a fixed combination containing the same standardized extract of Berberis aristata plus a standardized extract of Silybum marianum (titrated as >60% in silymarin), for a total intake of 1,000 mg/day of berberine and 210 mg/day of silymarin. RESULTS: Both treatments similarly improved fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, and liver enzyme levels, whereas glycosylated hemoglobin (HbA1c) values were reduced to a greater extent by the fixed combination. CONCLUSION: The association of berberine and silymarin demonstrated to be more effective than berberine alone in reducing HbA1c, when administered at the same dose and in the form of standardized extracts in type 2 diabetic patients.

Physical activity for the prevention and treatment of metabolic disorders.

Metabolic syndrome and its various features (obesity, hypertension, dyslipidemia, diabetes, and nonalcoholic fatty liver disease) are increasing worldwide and constitute a severe risk for the sustainability of the present universal Italian health care system. Lifestyle interventions should be the first therapeutic strategy to prevent/treat metabolic diseases, far before pharmacologic treatment. The role of diet and weight loss has been fully ascertained, whereas the role of physical activity is frequently overlooked both by physicians and by patients. Physical activity has favorable effects on all components of the metabolic syndrome and on the resulting cardiovascular risk, the cornerstone in the development of cardiometabolic diseases. The quantity and the frequency of physical activity necessary to produce beneficial effects has not been defined as yet, but brisk walking is considered particularly appropriate, as it can be practiced by a large number of individuals, without any additional cost, and has a low rate of injury. The effects of exercise and leisure time physical activity extend from prevention to treatment of the various components of the metabolic syndrome, as well as to mood and quality of life. Any effort should be done to favor adherence to protocols of physical activity in the community.

Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease.

BACKGROUNDS & AIMS: Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. METHODS: We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. RESULTS: The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. CONCLUSIONS: NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies.

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.

Prevalence of sexual dysfunction among postmenopausal women with and without metabolic syndrome.

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. 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 <23 and FSDS was >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.

Managing the combination of nonalcoholic fatty liver disease and metabolic syndrome.

INTRODUCTION: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies. AREAS COVERED: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience. EXPERT OPINION: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory.

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.

Treatment of non-alcoholic fatty liver disease with focus on emerging drugs.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common causes of chronic liver disease worldwide. The economic and social cost of disease is very high and there is a need for effective treatments. AREAS COVERED: The available and potential future treatments for NAFLD are reviewed. EXPERT OPINION: Weight loss remains the cornerstone of treatment of hepatic steatosis, but difficult to pursue. A pragmatic approach relies on generic recommendations for weight loss and physical activity in the whole population and limiting interventions to subject at risk of disease progression, but the type of preferred treatment remains a matter of debate. The large number and mechanistic diversity of drugs that have so far been investigated bear testimony to the lack of a specific, effective agent. Insulin resistance remains the pivotal alteration responsible for liver disease and its progression and insulin sensitizers are regarded as the treatment of choice. Several ongoing studies are testing the effectiveness of new approaches on histological outcomes and new metabolic pathways are under scrutiny.

Cognitive-behavioral treatment of nonalcoholic Fatty liver disease: a propensity score-adjusted observational study.

The effectiveness of cognitive-behavior treatment (CBT) in nonalcoholic fatty liver disease (NAFLD), largely related to overweight/obesity and considered the hepatic expression of the metabolic syndrome (MS), has so far been tested in very limited samples. In a tertiary referral center, consecutively observed NAFLD subjects were offered a CBT program aimed at weight loss and increased physical activity, based on 13 group sessions; 68 cases entered the treatment protocol, those who refused (n = 82) were given recommendations for diet and physical activity. Treatment goals (weight loss ≥7% initial body weight, normalization of liver enzymes, and improved parameters of MS) were tested by logistic regression at 6 months (all cases) and at 2 years, both on intention-to-treat and in completers (Diet, 78; CBT, 65). The results were adjusted for the propensity score of attending the CBT program, based on civil, anthropometric and clinical variables. At baseline the CBT group had a larger prevalence of obesity and more severe insulin resistance (homeostasis model assessment (HOMA)). At follow-up, CBT was associated with a higher probability of weight loss and normal liver enzymes (6-month: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.15-5.69; 2-year intention-to-treat: OR, 3.57, 95% CI, 1.59-8.00), after adjustment for propensity and changes in body weight. A similar trend was observed in the outcome goals of insulin resistance and the score of MS, which were both reduced. In conclusion, subjects with NAFLD participating in a CBT program significantly improve their general and liver parameters. The beneficial effects are largely maintained at 2-year follow-up, in keeping with the lifestyle-related pathogenesis of disease.

Metabolic syndrome and insulin resistance in subjects with morbid obesity.

BACKGROUND: There is evidence that a group of subjects with obesity fits the characteristics of metabolically healthy but obese population. We aimed to assess the prevalence of the metabolic syndrome (MS) in nondiabetic subjects with morbid obesity (body mass index (BMI) > or = 40 kg/m2) and its correlation with insulin resistance. METHODS: We analyzed the data of 211 patients (55 males and 156 females) with morbid obesity and without overt diabetes, consecutive referred for weight loss management. All subjects underwent an oral glucose tolerance test, and insulin resistance was calculated by the homeostasis model assessment (HOMA) at baseline and by the oral glucose insulin sensitivity (OGIS) during the glucose and insulin curve. Clinical and biochemical features of MS were also determined. RESULTS: The criteria for MS were fulfilled in 74% of cases, and 10 patients had obesity as the sole feature. HOMA-R was normal in 26% of cases, whereas, OGIS was normal only in three females. HOMA-R and OGIS significantly differed in relation to the presence of MS, and a trend was observed in both tests as function of the number of factors of MS (P < 0.001). At logistic regression analysis, after adjustment for age, sex, BMI at age 20 years, present BMI, and waist circumference, OGIS was the only parameter of insulin resistance significantly associated with MS (odds ratio, 2.42; 95% confidence interval, 1.63-3.60). CONCLUSIONS: A small number of metabolically healthy, but obese cases exist also in the subgroup of patients with morbid obesity in which insulin resistance maintains its pivotal role.

Obesity-associated liver disease.

CONTEXT: In the last few years, several data have accumulated suggesting that obesity may be associated with liver disease and disease progression. Accordingly, the worldwide epidemic of obesity is likely to become a relevant source of morbidity and mortality in the general population. EVIDENCE ACQUISITION: We reviewed the literature on two main issues: 1) the evidence that obesity carries out an increased risk of liver disease, both in the general population and in selected cohorts; and 2) the evidence that obesity is a risk factor for nonalcoholic fatty liver disease and its progression in a series observed in liver units. EVIDENCE SYNTHESIS: The presence of obesity increases the risk of elevated liver enzymes by a factor of two to three, whereas the risk of steatosis at ultrasonography is increased by a factor of 3 in the presence of overweight and peaks at a factor of approximately 15 in the presence of obesity. Both cirrhosis (cryptogenic cirrhosis) and hepatocellular carcinoma are also associated with obesity in the general population. In patients with nonalcoholic fatty liver disease observed in liver units, obesity and weight gain are systematically associated with advanced fibrosis and fibrosis progression. CONCLUSION: 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.