Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians.

UNLABELLED: A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. CONCLUSION: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.

Low total testosterone is associated with increased risk of incident type 2 diabetes mellitus in men: results from the Study of Health in Pomerania (SHIP).

OBJECTIVE: There is increasing evidence suggesting that low total testosterone concentration is associated with incident type 2 diabetes mellitus (T2DM) in men. The aim of this study was to evaluate the association between total testosterone and incident T2DM in a large population-based cohort. METHODS: Of 2117 men at baseline, 1589 were followed up 5 years later. Low total testosterone concentration at baseline determined by <10th percentile (10-year age-strata) were used as a risk factor for incident T2DM at follow-up. To evaluate for potential non-response bias, drop out weights were used in sensitivity analysis. RESULTS: From 1339 men eligible for analyses, 68 (5.1%) developed T2DM. Men with low total testosterone concentration had an increased risk of developing T2DM (odds ratio [OR] 3.4, 95% CI 1.9-6.1), even after adjustment for age, waist circumference and smoking, OR 3.0; (95% CI 1.6-5.7). Recalculated weighted models revealed almost identical estimates indicating no relevant non-response bias. DISCUSSION: Our prospective findings suggest that low total testosterone concentration is associated with incident T2DM in men and might represent a biomarker that might causally be involved in the risk of T2DM. This underlines the importance of measuring total testosterone in men as the predominant male sex hormone.

Reported beverage consumed and alcohol-related diseases among male hospital inpatients with problem drinking.

AIMS: The aim of this study was to examine if problem drinkers have varying risks of having alcohol-related diseases according to their reported beverage consumed. METHODS: In a cross-sectional study all consecutive inpatients aged 18- 64 years from four general hospitals of one catchment area were systematically screened for alcohol use. A total of 1011 men with problem drinking were used for this study. Routine treatment diagnoses for all participants were provided by hospital physicians and were classified into three categories according to their alcohol-attributable fractions (AAF; AAF = 0; AAF < 1; AAF = 1). RESULTS: According to their reported beverage consumed, 53.0% of the participants were identified as exclusively beer drinkers, 14.1% exclusively spirits drinkers, 26.0% mixed beer and spirits drinkers and 6.9% individuals drinking wine exclusively or in combination with one or two other beverages (mixed wine drinkers). Compared to spirits drinkers and controlling for possible confounders (i.e. alcohol-associated characteristics, demographic variables), multinomial regressions revealed that beer drinkers, mixed beer and spirits drinkers, and mixed wine drinkers had lower odds of having diseases with AAF = 1 than spirits drinkers (e.g. for AAF = 1: beer versus spirits drinkers: OR = 0.42, CI: 0.25-0.72). Beer drinkers and mixed wine drinkers also had lower odds of having diseases with AAF < 1 than spirits drinkers (e.g. mixed wine versus spirits drinkers: OR = 0.36, CI: 0.18-0.72). CONCLUSIONS: These data suggest an association between the reported beverage consumed and alcohol-related diseases. Among hospitalized problem drinkers, spirits drinkers had the greatest risk of having diseases with AAF < 1 and with AAF = 1.

Dose-response relation between volume of drinking and alcohol-related diseases in male general hospital inpatients.

AIMS: Previous studies investigating dose-response relations between volume of drinking and diseases have focused on single diseases only. Until now, the relation between the drinking volume and the risk of having any alcohol-attributable disease is largely unknown. The aim of the present study is to investigate to what extent is the risk of diseases with different alcohol-attributable fractions (AAFs) predicted by daily alcohol consumption (> 120 g, 61-120 g vs 31-60 g). METHODS: The sample consisted of 805 inpatients classified as at-risk drinking, aged 18-64 years hailing from four general hospitals in North-eastern Germany. Inpatients were classified into three groups (AAF = 1, AAF < 1, AAF = 0). Group differences regarding alcohol-related variables, smoking, and demographics were analysed. A multinomial logistic regression analysis was conducted to predict the risk of diseases with AAF = 1 and AAF < 1. RESULTS: In our sample, 26.6% of the inpatients showed a disease with AAF = 1, while 20.2% had a disease with AAF < 1. Inpatients consuming > 120 g, and inpatients consuming 61-120 g revealed significantly higher odds for diseases with AAF = 1 compared to inpatients consuming 31-60 g (OR = 6.30, CI = 3.55-11.26; OR = 2.91, CI = 1.64-5.13). Regarding diseases with AAF < 1, inpatients consuming > 120 g revealed significantly higher odds compared to the inpatients consuming 31-60 g (OR = 1.97, CI = 1.15-3.37). CONCLUSION: A dose-response relation between the level of the drinking volume and the risk of diseases with AAF = 1 was found in this sample of inpatients from the general hospitals.

[Improving Health Care for Patients with Somatoform and Functional Disorders: A Collaborative Stepped Care Network (Sofu-Net)]. / Verbesserte Versorgung von Patienten mit somatoformen und funktionellen Störungen: Ein koordiniertes gestuftes Netzwerk (Sofu-Net).

The management of somatoform disorders in primary care is often limited due to low diagnostic accuracy, delayed referral to psychotherapy and overuse of health care. To address these difficulties, this study aimed to establish a collaborative stepped health care network (Sofu-Net). Sofu-Net was established among 41 primary care physicians, 35 psychotherapists and 8 mental health clinics. Baseline assessment in primary care showed elevated psychopathology and deficits in health care among patients with somatoform symptoms. Network partners provided positive evaluations of Sofu-Net.

The association between fatty liver disease and blood pressure in a population-based prospective longitudinal study.

OBJECTIVE: The aim of the present study was to investigate the association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population sample with prospective 5-year follow-up examinations. DESIGN AND METHODS: We used data from the Study of Health in Pomerania, conducted in the northeastern part of Germany. The study population comprised 3191 individuals aged 20-79 years. FLD was defined as the presence of a hyperechogenic pattern of the liver and increased serum alanine transferase (ALT) levels. RESULTS: Multivariable analyses revealed that FLD was associated with increased DBP and hypertension at baseline and with increased SBP and hypertension at follow-up. In individuals with FLD, the chance of hypertension at baseline and follow-up was three-fold higher [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.3-6.2 and OR 3.1; 95% CI 1.7-5.8, respectively] compared to individuals without FLD. In the subgroup of individuals not receiving antihypertensive medication, FLD was associated with all BP-related variables at baseline and follow-up. Analyses further suggest that these associations were independent of alcohol consumption and further confounders. CONCLUSION: FLD defined by liver hyperechogenity and increased ALT levels is associated with progression of BP over time and incident hypertension. In individuals with FLD, BP should be checked regularly and interventions addressing behavioural risk factors for FLD and hypertension should be initiated if necessary. Ultrasound should be implemented as a method to detect FLD in individuals with increased ALT levels in routine medical care.

Motivation to change risky drinking and motivation to seek help for alcohol risk drinking among general hospital inpatients with problem drinking and alcohol-related diseases.

OBJECTIVE: The objective of this study was to analyze motivation to change drinking behavior and motivation to seek help in general hospital inpatients with problem drinking and alcohol-related diseases. METHOD: The sample consisted of 294 general hospital inpatients aged 18-64 years. Inpatients with alcohol-attributable disease were classified according to its alcohol-attributable fraction (AAF; AAF=1, AAF<1 and AAF=0). Baseline differences in alcohol-related variables, demographics and motivation between the AAF groups were analyzed. Furthermore, differences in motivation to change, in motivation to seek help and in the amount of alcohol consumed from baseline to follow-up between the AAF groups were evaluated. RESULTS: During hospital stay, motivation to change was higher among inpatients with alcohol-attributable diseases than among inpatients who had no alcohol-attributable diseases [F(2)=18.40, P<.001]. Motivation to seek help was higher among inpatients with AAF=1 than among inpatients with AAF<1 and AAF=0 [F(2)=21.66, P<.001]. While motivation to change drinking behavior remained stable within 12 months of hospitalization, motivation to seek help decreased. The amount of alcohol consumed decreased in all three AAF groups. CONCLUSIONS: Data suggest that hospital stay seems to be a "teachable moment." Screening for problem drinking and motivation differentiated by AAFs might be a tool for early intervention.

Male at-risk drinkers with heavy episodic drinking: a subclinical diagnosis?

OBJECTIVE: The aim of this study was to examine to what extent general hospital inpatients with risky drinking patterns differ regarding alcohol-associated characteristics. In particular, we tested whether persons with at-risk and heavy episodic drinking (ARHE) differ from those persons with at-risk drinking only (AR) and heavy episodic drinking only (HE). METHOD: The participants were recruited using a two-stage sampling process: (1) screening and (2) diagnostic. All in-patients from four general hospitals, ages 18-64 years (N = 14,332), were systematically screened for alcohol use. For this study, men with AR, HE, or ARHE (n = 425) were used, and men with current alcohol dependence or alcohol abuse were excluded. The severity of the alcohol problem was assessed by the number of lifetime Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnostic criteria met. Among the participants' diseases, those that were 100% attributable to alcohol (assigned an alcohol-attributable fraction of 1 [AAF = 1]) were analyzed. RESULTS: Of the sample, 35.3% of the persons were identified with AR, 22.6% with HE, and 42.1% with ARHE. Multinomial logistic regression revealed that, when controlling for age, ARHE was associated with increased odds of having a more severe alcohol problem (odds ratio [OR] = 2.06, confidence interval [CI]: 1.23-3.45), using formal help (OR = 2.21, CI: 1.02-4.79), and having diseases with AAF = 1 (OR = 3.43, CI: 1.58-7.43), compared with AR. CONCLUSIONS: Among at-risk drinkers, persons with ARHE are a special subgroup because there appears to be an indication of a subclinical diagnosis. To provide adequate intervention, future research and clinical practice should distinguish between different risky drinking patterns.