Nonalcoholic fatty liver disease: an independent risk factor for colorectal neoplasia.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of insulin resistance (IR), and IR is associated with an increased risk of colorectal carcinoma (CRC). Increased echogenicity suggesting NAFLD is a frequent incidental finding on ultrasound examination. We aimed to systematically evaluate whether NAFLD is an independent risk factor for colonic neoplasia. PATIENTS AND METHODS: One thousand two hundred and eleven patients (603 males, 60.6 ± 9.6 years; 608 females, 61.1 ± 10.3 years) who underwent screening colonoscopy according to national screening recommendations for CRC were evaluated in a cross-sectional study. Colorectal adenomas were classified as tubular adenoma, advanced adenoma (villous features, size ≥ 1 cm or high-grade dysplasia) or carcinoma. NAFLD was diagnosed by increased echogenicity on ultrasound examination after serological exclusion of infectious, immunological, hereditary or alcoholic aetiology. RESULTS: Nonalcoholic fatty liver disease was diagnosed in 367 (60.8%) males and in 265 (43.5%) females. The total rate of adenomas was increased in subjects with NAFLD (243/367 vs. 107/236 in males, P = 0.010; 94/265 vs. 78/343 in females; P = 0.014). In particular, more tubular adenomas (127/367 vs. 56/236; P = 0.006), adenomas of the rectum (40/367 vs. 8/236; P = 0.004) and more cancers (6/367 vs. 1/236; P < 0.001) were observed in males with NAFLD. In females with NAFLD, more tubular adenomas (59/265 vs. 48/343; P = 0.011) and adenomas of the proximal colon (51/265 vs. 40/343; P = 0.041) were observed. Multivariate regression analyses demonstrated an independent association of colorectal adenomas with hepatic steatosis after adjustment for age, sex, body mass index and glucose intolerance (OR 1.47; 95% CI 1.079-2.003; P = 0.015). CONCLUSION: Patients with NAFLD undergoing screening colonoscopy reveal significantly more CRC precursor lesions and early CRC compared with subjects without NAFLD. This elevated risk is independent from other manifestations of IR. These findings suggest that detecting fatty liver on ultrasound should heighten the awareness for referral to screening colonoscopy.

Iron stores, liver transaminase levels and metabolic risk in healthy teenagers.

BACKGROUND: Iron overload may contribute to the pathogenesis of insulin resistance. We aimed to investigate the relationship among iron stores, liver transaminases and components of the metabolic syndrome in healthy teenagers in a cross-sectional study. MATERIAL AND METHODS: We determined body mass index (BMI), waist-to-hip-ratio (WHR), blood pressure, liver ultrasound, serum lipids, insulin, fasting glucose, liver transaminase levels, hsCRP, iron parameters in 325 of 341 (95.3%) students (234 men, 16.7 +/- 1.7 years; 91 women, 16.5 +/- 1.7 years) of one single high school. Male and female study participants were allocated to increasing quartiles of body iron stores as assessed by sTfr/ferritin and alanine aminotranspeptidase (ALT) levels, and the distribution of cardiometabolic risk factors along quartiles was analysed. Regression analysis was performed to confirm the independent relationship between parameters. RESULTS: In male students, BMI, WHR, systolic and diastolic blood pressure, serum triglyceride levels and hsCRP were higher in the top sTfR/ferritin and ALT quartiles compared with the lowest quartiles (P < 0.01 for all parameters). In female students, sTfR/ferritin were not associated with antropomorphic cardiometabolic risk factors but with insulin resistance (HOMA-IR, P = 0.046). Moreover, ALT levels were independently related to BMI, waist and hip circumference, systolic blood pressure, serum triglyceride and insulin concentrations (P < 0.05 for all parameters) in female students. CONCLUSION: These results provide evidence for linkage among body iron stores, transaminase activity and the prevalence of cardiometabolic risk factors in apparently healthy, non-obese adolescents even within the range of normal laboratory and anthropomorphic values and suggest that iron stores should be investigated as a potentially modifiable risk factor in healthy teenagers.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Effect of obesity and insulin sensitivity on adiponectin isoform distribution.

BACKGROUND: Adiponectin is an insulin-sensitizing, antiatherogenic and anti-inflammatory adipocytokine that circulates in three isoforms: a trimer [low-molecular weight (LMW)], a hexamer (trimer-dimer) of medium molecular weight (MMW) and a multimeric high molecular weight (HMW) isoform. Evidence is accumulating that HMW adiponectin is the active isoform of the adipocytokine. We investigated the impact of adipose tissue and insulin sensitivity on adiponectin isoform distribution. MATERIALS AND METHODS: One hundred and eighty-seven normolipidaemic, non-diabetic lean or obese subjects with or without insulin resistance participating in the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR) were included in the study. Insulin sensitivity was determined by the short insulin tolerance test and the homeostasis model assessment (HOMA) index. Serum adiponectin isoform distribution was determined by an enzyme immunoassay. RESULTS: Total adiponectin as well as HMW/total adiponectin ratio was significantly increased in female subjects. Circulating total adiponectin levels were lowest in obese patients due to reduced concentrations of HMW adiponectin. As determined by stepwise regression analysis, besides age and high density lipoprotein (HDL) cholesterol, visceral fat area and waist-to-hip ratio predicted concentrations of HMW adiponectin, while insulin sensitivity had no influence on either total adiponectin or its isoforms. CONCLUSIONS: Our results underline that determination of adiponectin isoforms are more useful than measurement of total adiponectin in clinical settings. Our data suggest that adiponectin concentrations are strongly associated with visceral fat area but not with insulin sensitivity. Thus, we hypothesize that insulin resistance is a consequence rather than the cause of hypoadiponectinaemia in obese subjects.

Gender- and site-specific differences of colorectal neoplasia relate to vitamin D.

BACKGROUND: The effect of vitamin D on colorectal adenomas may vary with regard to gender, localisation and histological type of the lesion. AIM: To define the role of vitamin D and gender in a Caucasian cohort of subjects undergoing screening colonoscopy after consideration of established risk factors. METHODS: One thousand five hundred and thirty-two subjects (813 males, 58.8 ± 9.7 years; 719 females, 59.7 ± 10.7 years) were allocated to tertiles of 25-hydroxyvitamin D3 [25(OH)D3 ] serum concentrations. The number, localisation, size and histology of the detected colonic lesions were recorded. RESULTS: Among men, no association was found between vitamin D and the total number, size and histological stage of adenomas at any site. In female subjects, less women with adenomas were found in the highest vitamin D tertile (N = 42/239; 17.2%) as compared to the low vitamin D group (N = 60/240; 25.0%; P = 0.035). In particular, the number of women with adenomas in the proximal colon was significantly lower in the highest tertile (N = 21/239, 8.8%) compared to the low vitamin D group (N = 41/240; 17.1%; P = 0.007). The rates at other sites were not different. The inverse association of vitamin D serum concentrations with the presence of adenomas in the proximal colon was maintained after adjustment for potential confounders. In 80 women on vitamin D supplementation, the rate of adenomas was lower compared to those not on supplementation (3/80; 3.8%; vs. 90/719; 12.5%; P = 0.016). CONCLUSIONS: A potential preventive effect of vitamin D on colorectal adenomas was found in the proximal colon in women. This observation is supported by further decrease of lesions in the proximal colon of women on vitamin D supplementation.

Intima media thickness of carotid arteries is reduced in heterozygous carriers of the Gly972Arg variant in the insulin receptor substrate-1 gene.

BACKGROUND: The Gly972Arg mutation in the IRS-1 gene has been found to be associated with insulin resistance and type II diabetes. A recently published study described an association between the Arg allele and an increased risk for coronary artery disease. In the present study we asked whether the presence of the codon 972 mutation in the IRS-1 gene is associated with higher IMT values of the carotid arteries. MATERIALS AND METHODS: To address this question, genotypes of the codon 972 polymorphism were determined in 1018 healthy unrelated individuals aged 40-65 years. Three homozygous carriers of the mutation were excluded for statistical analysis. In all subjects, intima media thickness (IMT) and B-scores of carotid arteries as well as a large number of metabolic parameters were determined. RESULTS: Heterozygous carriers of the Arg972 allele exhibited significantly lower IMT and B-score values than noncarriers. Total cholesterol, LDL-cholesterol and serum levels of apolipoprotein B were significantly lower in the carriers. Furthermore, a significant interaction between Gly972Arg-carrier status and mean daytime 24-h systolic blood pressure with regard to IMT could be observed; carriers with a systolic blood pressure above the median had lower IMT values than carriers with a systolic blood pressure equal or below the median. All these effects were more pronounced in females and remained significant after adjustment for sex, age, BMI, systolic blood pressure and serum apolipoprotein B levels. No significant differences between the carriers and the noncarriers could be found for BMI, insulin sensitivity or frequency of type II diabetes. CONCLUSIONS: The results of our study demonstrate that the presence of the Arg972 allele is associated with lower IMT values of the carotid arteries. This finding is partly explained by lower serum levels of apolipoprotein B in carriers. The protective effect of the Gly972 Arg mutation seems to be stronger in the presence of a higher systolic blood pressure. Our data contradict previous findings suggesting an increased risk for insulin resistance, type II diabetes and atherosclerotic vascular disease in carriers of the mutation.