Olfactory dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: diabetic complications and olfactory dysfunction (OD) in patients with type 2 diabetes mellitus (T2DM) seem related. This study aims to evaluate the prevalence of OD in T2DM patients and to analyze its relationship with diabetic complications. METHODS: 130 T2DM patients and 100 comparable controls were enrolled. Olfaction was evaluated using the Extended Smell Test (TDI) and the Italian brief Questionnaire of Olfactory Disorders - Brief-IT-QOD. T2DM patients were divided into: "Group 1", patients with no complications, and "Group 2", patients with at least one diabetic complication. Non-parametric tests were used. Machine learning algorithms were applied to explore which variables were most important in predicting the presence of OD in T2DM. RESULTS: The prevalence of OD was significantly higher in Group 2 than in controls (71.4% vs 30%) and in Group 1 (71.4% vs 43.3%). However, when comparing the TDI scores between Group 1 and 2 the only significant difference was found for the discrimination scale and not for the identification and threshold scales. Brief-IT-QOD scores were significantly higher in Group 2 than in controls. The Random Forest and variable importance algorithms highlighted the relevance of LDL, glycated hemoglobin, type of complication (macrovascular) and age in determining OD in T2DM. The last three variables were included in a nomogram for the prediction of OD risk in T2DM. CONCLUSIONS: T2DM patients with diabetic complications are more frequently affected by OD. Poor glycemic control, LDL values, age and presence of macrovascular complications are the more important factors in determining OD in T2DM patients.

Hungry brains: A meta-analytical review of brain activation imaging studies on food perception and appetite in obese individuals.

The dysregulation of food intake in chronic obesity has been explained by different theories. To assess their explanatory power, we meta-analyzed 22 brain-activation imaging studies. We found that obese individuals exhibit hyper-responsivity of the brain regions involved in taste and reward for food-related stimuli. Consistent with a Reward Surfeit Hypothesis, obese individuals exhibit a ventral striatum hyper-responsivity in response to pure tastes, particularly when fasting. Furthermore, we found that obese subjects display more frequent ventral striatal activation for visual food cues when satiated: this continued processing within the reward system, together with the aforementioned evidence, is compatible with the Incentive Sensitization Theory. On the other hand, we did not find univocal evidence in favor of a Reward Deficit Hypothesis nor for a systematic deficit of inhibitory cognitive control. We conclude that the available brain activation data on the dysregulated food intake and food-related behavior in chronic obesity can be best framed within an Incentive Sensitization Theory. Implications of these findings for a brain-based therapy of obesity are briefly discussed.

A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans.

Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species.

Active Subjects With Autoimmune Type 1 Diabetes Have Better Metabolic Profiles Than Sedentary Controls.

Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (-24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.

The effects of alcohol on gastrointestinal tract, liver and pancreas: evidence-based suggestions for clinical management.

Alcohol has a direct impact on the digestive system due to its contact with mucosal lining and interference with digestive functions. Various diseases of the gastrointestinal tract, including tumors, may be related to an excess of alcohol intake and the relationship between alcohol abuse and hepatic and pancreatic damage is well established. According to WHO, alcohol and alcohol-related diseases represent a major health problem and will probably continue to do so in the foreseeable future. In this review, we summarize the present knowledge on clinically relevant alcohol-related problems in order to provide practicing physicians with evidence-based general suggestions which might help in the management of alcohol-related gastrointestinal disorders. A thorough clinical history together with a number of questionnaires are essential for detecting alcohol dependence or abuse. Biochemical tests (nonspecific and specific) have been considered to be less sensitive than questionnaires in screening for alcohol abuse, but they may be useful in identifying relapses. Protracted behavior modification, cognitive behavioral therapy, psychological counseling, and mutual support groups have been considered the most effective long-term treatments. Several drugs have been developed that are able to interfere with the neurotransmitters involved in craving mechanisms, and we summarize the evidence of their efficacy to increase abstinence and to prevent relapse.

Review article: Alcohol and gut microbiota - the possible role of gut microbiota modulation in the treatment of alcoholic liver disease.

BACKGROUND: Alcohol abuse represents the most common cause of liver disease in the Western countries. Pre-clinical and clinical studies showed that alcohol consumption affects amount and composition of gut microbiota. Moreover, gut flora plays an important role in the pathogenesis of alcoholic liver injury. AIM: To review the relationship between alcohol administration and changes on gut microbiota, its involvement in the pathogenesis of alcoholic liver disease, and how gut microbiota modulation could be a target for the treatment of alcoholic liver disease. METHODS: Articles were identified using the PubMed database with the search terms 'Alcohol', 'Gut Microbiota', 'Alcoholic liver disease', 'Probiotic', 'Prebiotic', 'Symbiotic' and 'Antibiotic'. English-language articles were screened for relevance. Full review of publications for the relevant studies was conducted, including additional publications that were identified from individual article reference lists. RESULTS: Alcohol abuse induces changes in the composition of gut microbiota, although the exact mechanism for this alteration is not well known. The translocation of bacterial products into the portal blood appears to play a key role in alcohol-induced liver damage. Several studies show that the modulation of gut microbiota seem to be a promising strategy to reduce alcohol-induced liver injury. CONCLUSIONS: Further studies are needed to better understand the relationship between alcohol administration and changes in gut microbiota, and its involvement in alcoholic liver disease. Moreover larger studies are needed to confirm the preliminary results on the therapeutic effects of gut microbiota modulation.

Baclofen in the treatment of persistent hiccup: a case series.

BACKGROUND: Persistent hiccup is a worrying symptom both for patients, because of reduced quality of life, and for physicians, because of frustration for unsuccessful treatments. AIM: To test baclofen administration for the treatment of persistent hiccup. METHOD: We report a series of seven patients affected by persistent hiccup successfully treated with baclofen. RESULTS: Hiccup stopped in all patients after a single administration of the drug. CONCLUSIONS: Baclofen is a GABA(B) receptor agonist. It is conceivable that the reduction of dopamine release by GABA(B) receptor stimulation is able to interrupt hiccup's reflex arc.

Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection.

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients.

State and trait anxiety and depression in patients affected by gastrointestinal diseases: psychometric evaluation of 1641 patients referred to an internal medicine outpatient setting.

OBJECTIVES: To evaluate state and trait form of anxiety and current depression in patients affected by gastrointestinal diseases. METHODS: We studied 1641 outpatients with gastrointestinal disorders, consecutively referred to our Internal Medicine outpatients from 1997 to 2005. State and trait anxiety were assessed by the State and Trait Anxiety Inventory. Current depression was assessed by the Zung self-rating depression scale. RESULTS: Among patients, 1379 (84.1%) showed state anxiety, 1098 (67%) showed trait anxiety and 442 (27%) showed current depression. The number of gastrointestinal diseases was directly correlated to state anxiety (p < 0.001) and trait anxiety (p = 0.04). Females showed higher levels of anxiety and depression than males (p < 0.001). State anxiety was related to food allergies (p < 0.001), small intestinal bacterial overgrowth (SIBO) (p = 0.001), Hp infection (p = 0.01) and ulcerative colitis in active phase (p = 0.03). Trait anxiety was related to irritable bowel syndrome (IBS) (p < 0.001), Helicobacter pylori (Hp) infection (p = 0.001), food allergies (p = 0.001) and SIBO (p = 0.001). Current depression was related to IBS (p < 0.001) and coeliac disease (p = 0.01), SIBO (p = 0.02). A predicted probability of 0.77 +/- 0.16 to have state anxiety, of 0.66 +/- 0.12 to have trait anxiety and of 0.39 +/- 0.14 to have depression was found in these patients. CONCLUSIONS: Most of the patients who seek medical consultation for gastrointestinal problems show an associated affective disorder. These patients should be managed by a team including gastroenterologists, psychologists and/or psychiatrists, or by a gastroenterologist having expertise in the treatment of psychological disorders.

Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities.

Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes.

Cutaneous manifestations in celiac disease.

Celiac disease (CD) is an autoimmune gluten-dependent enteropathy characterized by atrophy of intestinal villi that improves after gluten-free diet (GFD). CD is often associated with extra-intestinal manifestations; among them, several skin diseases are described in CD patients. The present review reports all CD-associated skin manifestations described in the literature and tries to analyze the possible mechanisms involved in this association. The opportunity to evaluate the possible presence of CD in patients affected by skin disorders is discussed.