Statin withdrawal and health-related quality of life in a primary cardiovascular prevention cohort.

PURPOSE: While some work has been done on Health-Related Quality of Life (HRQoL) in statin users, none has focused specifically on statin-associated muscle symptoms (SAMS) sufferers. The objective was to assess self-reported HRQoL, before and after statin withdrawal, in patients reporting SAMS. We hypothesized that the presence of SAMS associated with decreased self-reported physical and mental well-being. METHODS: Patients (50 men/28 women [M/W], aged 49 ± 9 years [Mean ± SD]) in primary cardiovascular prevention were recruited into three cohorts: statin users with (SAMS, 29 M/18W) or without symptoms (No SAMS, 10 M/5W) and controls (11 M/5W). The Short Form 36 Health Survey (SF-36) was used to assess HRQoL. All variables were measured before and after 2 months of statin withdrawal, and repeated measures analyses were used to verify withdrawal and group effects as well as their interaction. RESULTS: SF-36 physical and mental component scores (respectively, PCS and MCS) were lower in the SAMS group compared with other groups (both p < 0.01). Statin withdrawal led to an increase in LDL cholesterol for statin users (+69.0%, p < 0.01) and an improvement in well-being in the SAMS group, other groups showing no change. A time x category interaction (p = 0.02) was seen for PCS and post hoc analyses showed that statin withdrawal improved PCS and MCS (respectively, +12.5% [ES 0.77] and +5.1% [ES 0.27], both p < 0.05) in the SAMS group. CONCLUSION: Patients self-reporting SAMS showed improved HRQoL following drug withdrawal, but this was mirrored by a rise in LDL cholesterol. These findings should be considered by clinicians in the evaluation and follow-up of treatment with statins.

Light quality and dormancy overcoming in seed germination of Echium plantagineum L. (Boraginaceae) / Qualidade da luz e superação de dormência na germinação de sementes de Echium plantagineum L. (Boraginaceae)

Abstract Light is considered a factor that influences the seed germination of many weed species, and it can signal whether the environmental conditions are favorable or are not favorable for germination. We aimed to study if there is an influence of light quality and dormancy overcoming in seed germination of Echium plantagineum L. We carried out a 2 x 6 factorial experiment, with and without dormancy overcoming with potassium nitrate followed by immersion in gibberellic acid; six light qualities, obtained through the light filters: blue, green, red, far-red, white light and absence of light. The evaluations performed were germination speed index (GSI), average germination time (AGT), germination at the four and 14 days after seeding (DAS), accumulated germination and relative frequency of germination. We observed significant interaction among the light qualities and seed dormancy overcoming or not for the studied variables. There was no significant effect of light qualities, in the evaluated variables, when performing dormancy overcoming, presenting germination above 90% in all the light qualities. However, without dormancy overcoming, we observed greater GSI, germination at four and 14 DAS for the red light filter with 5, 4, 29 and 45%, respectively. When the seeds were submitted to the absence of light, and without dormancy overcoming, there was only 7% of germination at 14 DAS. The seeds of E. plantagineum presented greater germination under incidence of red light, without dormancy overcoming, being classified as preferably positively photoblastics, provided that the dormancy is not overcome.

Resumo A luz é considerada um fator que influencia a germinação das sementes de muitas espécies de plantas daninhas, podendo sinalizar se as condições ambientais são favoráveis ou não para a germinação. Objetivou-se estudar se há influência da qualidade da luz e superação de dormência na germinação de sementes de Echium plantagineum L. Realizou-se um experimento fatorial 2 x 6, com e sem superação de dormência com nitrato de potássio seguido pela imersão em ácido giberélico; seis qualidades de luz, obtidas através de filtros de luz: azul, verde, vermelho, vermelho-distante, luz branca e ausência de luz. As avaliações realizadas foram índice de velocidade de germinação (IVG), tempo médio de germinação (TMG), germinação aos quatro e 14 dias após a semeadura (DAS), germinação acumulada e frequência relativa de germinação. Observou-se interação significativa entre as qualidades de luz e a superação ou não de dormência das sementes para as variáveis estudadas. Não houve efeito significativo das qualidades de luz, nas variáveis avaliadas, ao realizar superação de dormência, apresentando germinação acima de 90% em todas as qualidades de luz. Todavia, sem superação de dormência, observou-se maior IVG, germinação aos quatro e 14 DAS para o filtro de luz vermelha com 5,4, 29 e 45%, respectivamente. Quando as sementes foram submetidas à ausência de luz, e sem superação de dormência, houve apenas 7% de germinação aos 14 DAS. As sementes de E. plantagineum apresentam maior germinação sob incidência de luz vermelha, sem superação de dormência, sendo classificadas como fotoblásticas positivas preferenciais, desde que não seja superada a dormência.

Light quality and dormancy overcoming in seed germination of Echium plantagineum L. (Boraginaceae).

Light is considered a factor that influences the seed germination of many weed species, and it can signal whether the environmental conditions are favorable or are not favorable for germination. We aimed to study if there is an influence of light quality and dormancy overcoming in seed germination of Echium plantagineum L. We carried out a 2 x 6 factorial experiment, with and without dormancy overcoming with potassium nitrate followed by immersion in gibberellic acid; six light qualities, obtained through the light filters: blue, green, red, far-red, white light and absence of light. The evaluations performed were germination speed index (GSI), average germination time (AGT), germination at the four and 14 days after seeding (DAS), accumulated germination and relative frequency of germination. We observed significant interaction among the light qualities and seed dormancy overcoming or not for the studied variables. There was no significant effect of light qualities, in the evaluated variables, when performing dormancy overcoming, presenting germination above 90% in all the light qualities. However, without dormancy overcoming, we observed greater GSI, germination at four and 14 DAS for the red light filter with 5, 4, 29 and 45%, respectively. When the seeds were submitted to the absence of light, and without dormancy overcoming, there was only 7% of germination at 14 DAS. The seeds of E. plantagineum presented greater germination under incidence of red light, without dormancy overcoming, being classified as preferably positively photoblastics, provided that the dormancy is not overcome.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Light quality and dormancy overcoming in seed germination of Echium plantagineum L. (Boraginaceae)

Abstract Light is considered a factor that influences the seed germination of many weed species, and it can signal whether the environmental conditions are favorable or are not favorable for germination. We aimed to study if there is an influence of light quality and dormancy overcoming in seed germination of Echium plantagineum L. We carried out a 2 x 6 factorial experiment, with and without dormancy overcoming with potassium nitrate followed by immersion in gibberellic acid; six light qualities, obtained through the light filters: blue, green, red, far-red, white light and absence of light. The evaluations performed were germination speed index (GSI), average germination time (AGT), germination at the four and 14 days after seeding (DAS), accumulated germination and relative frequency of germination. We observed significant interaction among the light qualities and seed dormancy overcoming or not for the studied variables. There was no significant effect of light qualities, in the evaluated variables, when performing dormancy overcoming, presenting germination above 90% in all the light qualities. However, without dormancy overcoming, we observed greater GSI, germination at four and 14 DAS for the red light filter with 5, 4, 29 and 45%, respectively. When the seeds were submitted to the absence of light, and without dormancy overcoming, there was only 7% of germination at 14 DAS. The seeds of E. plantagineum presented greater germination under incidence of red light, without dormancy overcoming, being classified as preferably positively photoblastics, provided that the dormancy is not overcome.

Resumo A luz é considerada um fator que influencia a germinação das sementes de muitas espécies de plantas daninhas, podendo sinalizar se as condições ambientais são favoráveis ou não para a germinação. Objetivou-se estudar se há influência da qualidade da luz e superação de dormência na germinação de sementes de Echium plantagineum L. Realizou-se um experimento fatorial 2 x 6, com e sem superação de dormência com nitrato de potássio seguido pela imersão em ácido giberélico; seis qualidades de luz, obtidas através de filtros de luz: azul, verde, vermelho, vermelho-distante, luz branca e ausência de luz. As avaliações realizadas foram índice de velocidade de germinação (IVG), tempo médio de germinação (TMG), germinação aos quatro e 14 dias após a semeadura (DAS), germinação acumulada e frequência relativa de germinação. Observou-se interação significativa entre as qualidades de luz e a superação ou não de dormência das sementes para as variáveis estudadas. Não houve efeito significativo das qualidades de luz, nas variáveis avaliadas, ao realizar superação de dormência, apresentando germinação acima de 90% em todas as qualidades de luz. Todavia, sem superação de dormência, observou-se maior IVG, germinação aos quatro e 14 DAS para o filtro de luz vermelha com 5,4, 29 e 45%, respectivamente. Quando as sementes foram submetidas à ausência de luz, e sem superação de dormência, houve apenas 7% de germinação aos 14 DAS. As sementes de E. plantagineum apresentam maior germinação sob incidência de luz vermelha, sem superação de dormência, sendo classificadas como fotoblásticas positivas preferenciais, desde que não seja superada a dormência.

Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based cohorts: results from the KORA studies.

BACKGROUND: Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and antioxidative glycoprotein. Plasma apoA-IV levels are elevated in patients with primary chronic kidney disease (CKD) or renal failure. The association between apoA-IV and kidney function has not been investigated in the general population; therefore, we analysed this relationship in two large population-based cohorts. METHODS: Plasma apoA-IV concentrations were measured in the Cooperative Health Research in the Region of Augsburg (KORA) F3 (n = 3159) and KORA F4 (n = 3061) studies. CKD was defined by the serum creatinine-estimated glomerular filtration rate (eGFR) and/or urine albumin-to-creatinine ratio. RESULTS: Mean (±SD) apoA-IV concentration was 17.3 ± 4.7 mg dL(-1) in KORA F3 and 15.3 ± 4.3 mg dL(-1) in KORA F4. Fully adjusted linear mixed models revealed a significant association between apoA-IV concentration and lower eGFR in the third and fourth versus the first quartile of apoA-IV (ß = -1.78 mL min(-1) /1.73 m², P = 0.0003 and ß = -5.09 mL min(-1) /1.73 m², P = 2.83 × 10(-23) , respectively). ApoA-IV was significantly associated with an eGFR of <60 mL min(-1) /1.73 m², which was observed in 601 of the 6220 study participants [odds ratio (OR) 1.46, P = 0.03 and OR 3.47, P = 6.84 × 10(-15) for the third and fourth vs. the first quartile of apoA-IV, respectively]. Adding apoA-IV (fourth vs. first quartile) to the fully adjusted model significantly improved discrimination of eGFR <60 mL min(-1) /1.73 m² in KORA F3 [integrated discrimination improvement (IDI) 0.03, P = 1.30 × 10(-7) ] and KORA F4 (IDI 0.04, P = 1.32 × 10(-9) ) beyond classical risk factors for CKD. CONCLUSION: The present analysis in two population-based cohorts revealed that high plasma apoA-IV concentrations are strongly associated with low kidney function defined by eGFR independent of major CKD risk factors. ApoA-IV appears to be an early marker of impaired kidney function.

Association of low 25-hydroxyvitamin D levels with the frailty syndrome in an aged population: results from the KORA-age Augsburg study.

OBJECTIVES: Older adults often suffer from vitamin D deficiency and from the frailty syndrome charac-terized by different physical limitations, complicating independent everyday life. Previous studies have suggested a relationship between vitamin D status and the frailty syndrome, but results have been partly inconsistent, particularly regarding the shape of the association. Therefore, our aim was to further assess the association of 25-hydroxyvitamin D (25(OH)D) serum levels and frailty in older participants. DESIGN: Cross-sectional population-based study. PARTICIPANTS: The study population included 478 men and 462 women of the KORA (COoperative health research in the Region of Augsburg)-Age study born before 1944 examined in 2009. MEASUREMENTS: Classification of participants into different frailty states was performed according to the following criteria: weight loss, exhaustion, physical inactivity, slowness, and weakness. PARTICIPANTS who met 1-2 or ≥ 3 of the 5 criteria were classified as prefrail or frail, respectively. Total 25(OH)D was measured in non-fasting serum samples with an enhanced chemiluminescence immunoassay. Sequential logistic regression models adjusted for age, sex, season, lifestyle factors, diseases and biomarkers including parathyroid hormone (PTH) were calculated. RESULTS: High levels of 25(OH)D were inversely associated with being prefrail (N=351) or frail (N=38) in the model adjusted for age, sex, season and lifestyle factors. Compared to levels <15 ng/ml, odds ratios (ORs) (95% confidence intervals (CIs) were 0.52 (0.34-0.78) for levels of 15-<20 ng/ml, 0.55 (0.37-0.81) for levels of 20-<30 ng/ml and 0.32 (0.21-0.51) for levels ≥ 30 ng/ml. Additional adjustment for potential mediators including PTH only slightly attenuated these associations. For single frailty-components, significantly decreased ORs were found for exhaustion, physical inactivity and slowness comparing 25(OH)D levels ≥ 30 ng/ml with levels <15 ng/ml. CONCLUSION: Subjects with 25(OH)D serum levels ≥ 15 ng/ml were less frequently prefrail or frail.

The use of dietary supplements among older persons in southern Germany - results from the KORA-age study.

OBJECTIVES: Current population-based surveys in Europe on the prevalence of dietary supplement (DS) use in older individuals are scarce. The aim of the present study was to investigate patterns, prevalence and determinants of non-herbal DS use in aged subjects. Furthermore, the intake amounts of vitamins and minerals from supplements were assessed. DESIGN: Cross-sectional. SETTING: Data on supplement use were available from an age- and sex-stratified random sample of the German population-based KORA (Cooperative Health Research in the Region of Augsburg)-Age study. PARTICIPANTS: 1,079 persons who were born in or before the year 1943. MEASUREMENTS: Use of dietary supplements and medications during the last seven days was recorded in a face-to-face interview in 2009. Participants were asked to bring all packages of ingested preparations to the study center. Not only vitamin/mineral supplements, but also non-vitamin non-mineral non-herbal supplements and drugs containing vitamins and minerals were coded as DS. RESULTS: The age-standardized prevalence of DS intake was 54.3% in women and 33.8% in men, respectively. The most commonly supplemented mineral and vitamin, respectively, was magnesium (31.9%) and vitamin D (21.5%) in women and magnesium (18.0%) and vitamin E (12.0%) in men. The highest intakes, compared to the German Dietary Reference Intakes, were reported for biotin, vitamin B6 and B1. Excessive intakes (equal or above the European Tolerable Upper Intake Levels (UL)) were observed especially for magnesium and vitamin E. 20.2% of the women and 32.5% of the men who took magnesium supplements regularly exceeded the UL for magnesium. In case of vitamin E this was true for 8.0% of the women and 13.6% of the men. Determinants of DS use were sex, education, smoking, physical activity, neurological diseases, and stroke. CONCLUSION: A high proportion of the general population aged 65 years and older in Southern Germany uses DS, especially supplements containing vitamins/minerals. The supplementation of vitamin D can be regarded as favorable in this age group, whereas the excessive intakes of vitamin E might be a cause of concern.

Medication costs by glucose tolerance stage in younger and older women and men: results from the population-based KORA survey in Germany.

To estimate medication costs in individuals with diagnosed diabetes, undetected diabetes, impaired glucose regulation and normal blood glucose values in a population-based sample by age and sex.Using the KORA F4 follow-up survey, conducted in 2006-2008 (n=2611, age 40-82 years), we identified individuals' glucose tolerance status by means of an oral glucose tolerance test. We assessed all medications taken regularly, calculated age-sex specific medication costs and estimated cost ratios for total, total without antihyperglycemic drugs, and cardiovascular medication, using multiple 2-part regression models.Compared to individuals with normal glucose values, costs were increased in known diabetes, undetected diabetes and impaired glucose regulation, which was more pronounced in participants aged 40-59 years than in those aged 60-82 years (cost ratios for all medications: 40-59 years: 2.85; 95%-confidence interval: 1.78-4.54, 2.00; 1.22-3.29 and 1.53; 1.12-2.09; 60-82 years: 2.04; 1.71-2.43, 1.17; 0.90-1.51 and 1.09; 0.94-1.28). Compared to individuals with diagnosed diabetes, costs were significantly lower among individuals with impaired glucose regulation across all age and sex strata, also when antihyperglycemic medication was excluded (40-59 years: 0.60; 0.36-0.98, 60-82 years: 0.74; 0.60-0.90; men: 0.72; 0.56-0.93; women: 0.72; 0.54-0.96).We could quantify age- and sex-specific medication costs and cost ratios in individuals with diagnosed diabetes, undetected diabetes and impaired glucose regulation compared to those with normal glucose values, using data of a population-based sample, with oral glucose tolerance test-based identification of diabetes states. These results may help to validly estimate cost-effectiveness of screening and early treatment or prevention of diabetes.

[Carcinoma of the pararenal gland infiltrating the surrounding tissue and involving the inferior vena cava]. / Organüberschreitendes Nebennierenrindenkarzinom mit Beteiligung der Vena cava inferior.

UNLABELLED: ▼HISTORY AND ADMISSION FI NDINGS: A 61-year-old woman presented with a 2-month-history of progressive deterioration, increasing exertional dyspnoea and pain in the right upper abdomen (past medical history: bronchial asthma and hypertension). The physical examination showed mild generalized weakness, tenderness in the right upper abdomen, and ascites. INVESTIGATIONS: Laboratory studies did not reveal any hormonal abnormalities. A CT angiogram revealed a mass of the right adrenal gland with distinct invasion into the inferior vena cava, and tumour thrombosis that extended proximally into the right atrium. Distally, the tumour ended at the caudate lobe of the liver with an extensive peripherally engulfed thrombus from the inferior vena cava down to the common iliac -veins. TREATMENT AND COURSE: An open right adrenalectomy with resection of the periadrenal tissue and exstirpation of the intracaval tumour thrombus (by cavotomy under digital occlusion of the blood flow from the vena cava into the right atrium - cardiac surgeon) was carried out with no significant postoperative complications. Subsequently, the patient underwent adjuvant mitotane therapy for 3 years. So far, no recurrence has occurred during a course of 7 years. CONCLUSION: Tumour induced thrombotic occlusion of the inferior vena cava and other veins is rare, especially with right atrium involvement. In the absence of other effective treatment options, the combination of radical resection and adjuvant mitotane therapy remains the only successful curative treatment for primary invasive pararenal gland carcinoma.

Patient time costs attributable to healthcare use in diabetes: results from the population-based KORA survey in Germany.

AIMS: Patient time costs have been described to be substantial; however, data are highly limited. We estimated patient time costs attributable to outpatient and inpatient care in study participants with diagnosed diabetes, previously undetected diabetes, impaired glucose regulation and normal glucose tolerance. METHODS: Using data of the population-based KORA S4 study (55-74 years, random sample of n = 350), we identified participants' stage of glucose tolerance by oral glucose tolerance test. To estimate mean patient time costs per year (crude and standardized with respect to age and sex), we used data regarding time spent with ambulatory visits including travel and waiting time and with hospital stays (time valued at a 2011 net wage rate of €20.63/h). The observation period was 24 weeks and data were extrapolated to 1 year. RESULTS: Eighty-nine to 97% of participants in the four groups (diagnosed diabetes, undetected diabetes, impaired glucose regulation and normal glucose tolerance.) had at least one physician contact and 4-14% at least one hospital admission during the observation period. Patient time [h/year (95% CI)] was 102.0 (33.7-254.8), 53.8 (15.0-236.7), 59.3 (25.1-146.8) and 28.6 (21.1-43.7), respectively. Age-sex standardized patient time costs per year (95% CI) were €2447.1 (804.5-6143.6), €880.4 (259.1-3606.7), €1151.6 (454.6-2957.6) and €589.2 (435.8-904.8). CONCLUSIONS: Patient time costs were substantial--even higher than medication costs in the same study population. They are higher in participants with diagnosed diabetes, but also in those with undetected diabetes and impaired glucose regulation compared with those with normal glucose tolerance. Research is needed in larger populations to receive more precise and certain estimates that can be used in health economic evaluation.

[Organ-invasive carcinoma of the pararenal gland involving the inferior vena cava: successful curative and interdisciplinary surgical management]. / Organüberschreitendes Nebennierenrindenkarzinom mit Beteiligung der Vena cava inferior. Kurativ erfolgreiches interdisziplinär-operatives Management.

HISTORY AND ADMISSION FINDINGS: A 61-year-old woman presented with a 2-month-history of progressive deterioration, increasing exertional dyspnoea and pain in the right upper abdomen (past medical history: bronchial asthma and hypertension). The physical examination showed mild generalized weakness, tenderness in the right upper abdomen, and ascites. INVESTIGATIONS: Laboratory studies did not reveal any hormonal abnormalities. A CT angiogram revealed a mass of the right adrenal gland with distinct invasion into the inferior vena cava, and tumour thrombosis that extended proximally into the right atrium. Distally, the tumour ended at the caudate lobe of the liver with an extensive peripherally engulfed thrombus from the inferior vena cava down to the common iliac veins. TREATMENT AND COURSE: An open right adrenalectomy with resection of the periadrenal tissue and extirpation of the intracaval tumour thrombus (by cavotomy under digital occlusion of the blood flow from the vena cava into the right atrium) was carried out with no significant postoperative complications. Subsequently, the patient underwent adjuvant mitotane therapy for three years. So far, no recurrence has occurred during a course of 7 years. CONCLUSION: Tumour induced thrombotic occlusion of the inferior vena cava and other veins is rare, especially with right atrium involvement. In the absence of other effective treatment options, the combination of radical resection and adjuvant mitotane therapy remains the only successful curative treatment for primary invasive adrenal gland carcinoma.

Serum potassium is associated with prediabetes and newly diagnosed diabetes in hypertensive adults from the general population: the KORA F4-study.

AIMS/HYPOTHESIS: Evidence suggests that low serum potassium concentrations or hypokalaemia induced by the intake of diuretics are associated with incident diabetes and increased risk for diabetes in persons with hypertension. We examined a possible association between serum potassium and prediabetes (defined as isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT] or combined IFG/IGT), as well as known and newly diagnosed diabetes (NDD), in 32- to 81-year-old men and women with and without hypertension. METHODS: This cross-sectional analysis was based on 2,948 participants in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study conducted in 2006-2008 in southern Germany. Serum concentrations of potassium were measured by indirect potentiometry. RESULTS: In the total sample there was no association between serum potassium concentrations and prediabetes. In hypertensive persons however serum potassium levels in the first and second quartile compared with the highest quartile were independently significantly associated with prediabetes after multivariable adjustment (OR for prediabetes, 2.02 [95% CI 1.27, 3.21] for quartile 2 and 2.00 [95% CI 1.27, 3.15] for quartile 1), while in persons without hypertension no association was found. In multinomial logistic regression analysis these findings could be confirmed. In hypertensive participants after multivariable adjustment the associations were statistically significant for i-IGT and NDD (i-IGT OR 1.23; NDD OR 1.41). However, in non-hypertensive persons, all associations between serum potassium levels and each of the categories of impaired glucose regulation were non-significant. CONCLUSIONS/INTERPRETATION: Serum potassium levels were independently associated with prediabetes and NDD in hypertensive adults from the general population.

Genetic variation in the vaspin gene affects circulating serum vaspin concentrations.

OBJECTIVE: Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine potentially linking obesity, insulin resistance and type 2 diabetes. Here, we searched for genetic determinants that could explain the variability in serum vaspin concentrations. RESEARCH DESIGN AND METHODS: First, we conducted a genome-wide association study (GWAS) for serum vaspin in the Sorbs cohort (N=826). Subsequently, 26 single-nucleotide polymorphisms (SNPs) covering genetic variation in the vaspin locus were genotyped in the Sorbs. In addition, we measured serum vaspin concentrations in 1806 samples from Augsburg/the Cooperative Health Research in the Region of Augsburg (KORA) for replication of the association signals. Finally, we conducted association analyses of vaspin SNPs with metabolic traits in the Sorbs (N=1013), KORA (N=1813) and a further cohort from Germany (Leipzig: N=1857). RESULTS: Six SNPs mapping between serpinA1 and serpinA4, including the vaspin locus, on chromosome 14 reached P-values < or = 10(-8) in the GWAS in the Sorbs. The fine mapping of variants within the vaspin locus in the Sorbs and subsequent replication in the KORA sample revealed several SNPs significantly associated with serum vaspin concentrations reaching P-values of up to 10(-35). However, no significant association with type 2 diabetes or related traits was found in either cohort after the Bonferroni correction for multiple comparisons. CONCLUSION: Our data show that the variability in serum vaspin concentrations might be explained by its genetic variants.

Age at menarche is associated with prediabetes and diabetes in women (aged 32-81 years) from the general population: the KORA F4 Study.

AIMS/HYPOTHESIS: The aim of this study was to examine the association between age at menarche and prediabetes as well as diabetes, considering confounding factors and the possible mediating role of adult obesity. METHODS: This cross-sectional study analysed data on 1,503 women aged 32-81 years from the German population-based KORA (Cooperative Health Research in the Region of Augsburg, South Germany) F4 Study (2006-2008). Data were collected by standardised interviews, physical examinations, and whole blood and serum measurements, including administration of an OGTT in non-diabetic participants. RESULTS: Of the 1,503 women, 226 showed a prediabetic state (impaired fasting glucose and/or impaired glucose tolerance) and 140 persons had diabetes (45 participants with previously undiagnosed diabetes and 95 with known diabetes). In Poisson regression analysis, age at menarche was significantly inversely associated with prediabetes or diabetes after adjustment for year of birth (RR 0.88; 95% CI 0.82, 0.94, p < 0.0001 per additional year of menarche) and after additional adjustment for a number of confounding factors (RR 0.88; 95% CI 0.83, 0.94, p = 0.0001). Further adjustment for current BMI slightly attenuated the association with prediabetes or diabetes (RR 0.89; 95% CI 0.83, 0.95, p = 0.0009), but the association remained clearly significant. CONCLUSIONS/INTERPRETATION: Age at menarche seems to be inversely associated with prediabetes and diabetes independent of confounding factors including current BMI. Women at risk for diabetes might be identified by a history of young age at menarche.

Genes and lifestyle factors in obesity: results from 12,462 subjects from MONICA/KORA.

BACKGROUND: Data from meta-analyses of genome-wide association studies provided evidence for an association of polymorphisms with body mass index (BMI), and gene expression results indicated a role of these variants in the hypothalamus. It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure. OBJECTIVE: It was our aim to investigate the association of these genetic factors with BMI in a large homogenous population-based sample to explore the association of these polymorphisms with lifestyle factors related to nutritional intake or energy expenditure, and whether such lifestyle factors could be mediators of the detected single-nucleotide polymorphism (SNP)-association with BMI. It was a further aim to compare the proportion of BMI explained by genetic factors with the one explained by lifestyle factors. DESIGN: The association of seven polymorphisms in or near the genes NEGR1, TMEM18, MTCH2, FTO, MC4R, SH2B1 and KCTD15 was analyzed in 12,462 subjects from the population-based MONICA/KORA Augsburg study. Information on lifestyle factors was based on standardized questionnaires. For statistical analysis, regression-based models were used. RESULTS: The minor allele of polymorphism rs6548238 C>T (TMEM18) was associated with lower BMI (-0.418 kg m(-2), P=1.22 × 10(-8)), and of polymorphisms rs9935401 G>A (FTO) and rs7498665 A>G (SH2B1) with increased BMI (0.290 kg m(-2), P=2.85 × 10(-7) and 0.145 kg m(-2), P=9.83 × 10(-3)). The other polymorphisms were not significantly associated. Lifestyle factors were correlated with BMI and explained 0.037% of the BMI variance as compared with 0.006% of explained variance by the associated genetic factors. The genetic variants associated with BMI were not significantly associated with lifestyle factors and there was no evidence of lifestyle factors mediating the SNP-BMI association. CONCLUSIONS: Our data first confirm the findings for TMEM18 with BMI in a single study on adults and also confirm the findings for FTO and SH2B1. There was no evidence for a direct SNP-lifestyle association.

Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies.

Genome-wide association (GWA) studies identified novel gene variants that are associated with type 2 diabetes. However, results were not always consistent across different populations. Thus, the aims of this study were (i) to replicate findings from previous GWA studies in mainly Northern European populations using data from the German KORA 500 K diabetes project and (ii) to assess the impact of BMI on associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. The KORA 500 K diabetes project includes 433 cases with validated type 2 diabetes and 1 438 nondiabetic controls from two population-based KORA surveys. Genotyping was performed using the Affymetrix GeneChip Human Mapping 500 K Array Set. We investigated associations between SNPs and type 2 diabetes in 10 genes that have been reported to increase the risk of type 2 diabetes or were in complete or near-complete linkage disequilibrium with these variants. SNPs in the CDKAL1 gene showed the strongest association with type 2 diabetes [range of age and sex-adjusted odds ratios (OR): 1.30-1.39, p-values 0.0008-0.0004]. In addition, we found evidence for association of SNPs in the genes PPARG, IGF2BP2, HHEX, TCF7L2, and FTO with type 2 diabetes in the same directions as previously described (p<0.05), but not for WFS1, CDKN2A/B, KCNJ11, or EXT2. Adjustment for BMI slightly strengthened the link between CDKAL1 and type 2 diabetes, but had almost no impact on the other associations. We conclude that gene variants of CDKAL1, PPARG, IGF2BP2, HHEX, TCF7L2, and FTO predispose to type 2 diabetes in the German KORA 500 K study population. These associations appear to be independent of BMI.

Surgery of inferior vena cava associated malignant tumor lesions.

BACKGROUND: Tumor lesions of the inferior vena cava (IVC) can originate from the vein or can develop by malignant tumor infiltration from the surrounding tissue. In this context, particular attention should be paid to tumor lesions with pegs into or within the IVC. The aim of this series of a single surgical center was to analyze the perioperative management, the individual-specific and -adapted surgical technique, as well as the outcome including prognostic considerations in IVC-associated malignant tumor lesions. PATIENTS AND METHODS: Over a 6-year time period, all consecutive patients with IVC-associated malignant tumor lesions and their patient- and finding-specific characteristics were registered, data and parameters of the diagnostic and therapeutic management were documented, and both the short- and long-term outcomes (complication rate, perioperative morbidity/mortality, tumor recurrence rate, survival) were assessed with periodic follow-up investigations. RESULTS: Overall, 12 patients were enrolled in the study from 1/1/2001-31/12/2006:6 primary IVC-tumors (leiomyosarcomas, 50%) and 6 secondary IVC-tumors (2 retroperitoneal tumor lesions, 16.7%, 3 renal cell carcinomas 25% and 1 carcinoma of the adrenal gland, 8.3%). 4 of the secondary tumors had pegs into the IVC. The RO resection rate was 83%. The perioperative morbidity was 33%; whereas, the hospital mortality was 8.3% (n = 1). Surgical reconstruction of IVC was achieved in each case (100%). There was a mean postoperative observation period of 20 months (range, 1-58 months). Complete follow-up documentation was obtained for all of the patients (100%). Three patients experienced recurrent tumor growth (27.5% out of n = 11). While the overall mortality through the follow up observation period was 27.5%, the tumor-specific mortality was 16%. CONCLUSIONS: The primary surgical aim is RO resection to provide a long-term outcome with no tumor recurrence including the reconstruction of the IVC based on a reasonable risk-to-benefit ratio. The favorable outcome of this case series demonstrates that IVC-associated tumor lesions can be approached if there is an appropriate expertise of the surgical team, a sufficient perioperative management and an adequate financial background with a reasonable survival rate. The variable prognosis of the various tumor lesions depends on tumor entity, stage, resection status and individual risk factors.

Genetic variants in the leukemia-associated Rho guanine nucleotide exchange factor (ARHGEF12) gene are not associated with T2DM and related parameters in Caucasians (KORA study).

OBJECTIVE: The aim of our study was to determine the variant pattern of the leukemia-associated Rho guanine nucleotide exchange factor (LARG, or ARHGEF12) gene and investigate whether LARG variants are associated with diabetes mellitus type 2 (T2DM), the metabolic syndrome (MetS), or related parameters such as insulin sensitivity in German Caucasians. DESIGN: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in the 55-74-year-old individuals of the population-based German Caucasian Cooperative Health Research in the region of Augsberg (KORA) survey 4 (S4). METHODS: Sequencing of Tyr1306Cys, which was of functional relevance in Pima Indians, in 48 randomly selected individuals and genotyping of 11 additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r(2)> or =0.8) were established and each block was statistically analyzed for association with metabolic traits. The association with T2DM and the MetS was analyzed by logistic regression in 1462 subjects, and HOMA-IR (homeostasis model assessment of insulin resistance) as a measure of insulin sensitivity was analyzed by the Kruskal-Wallis test in 1346 fasting subjects. RESULTS: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians, was not found in the KORA S4 population. Statistical analysis yielded no significant associations (P>0.05) between the analyzed LARG variants and T2DM, the MetS, or related parameters such as insulin sensitivity. CONCLUSIONS: Caucasian individuals and Pima Indians differ in their genetic variance pattern in the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity, or the MetS.

Effects of propofol and desflurane anaesthesia on the alveolar inflammatory response to one-lung ventilation.

BACKGROUND: One-lung ventilation (OLV) induces a pro-inflammatory response including cytokine release and leucocyte recruitment in the ventilated lung. Whether volatile or i.v. anaesthetics differentially modulate the alveolar inflammatory response to OLV is unclear. METHODS: Thirty patients, ASA II or III, undergoing open thoracic surgery were randomized to receive either propofol 4 mg kg(-1) h(-1) (n = 15) or 1 MAC desflurane in air (n = 15) during thoracic surgery. Analgesia was provided by i.v. infusion of remifentanil (0.25 microg kg(-1) min(-1)) in both groups. The patients were mechanically ventilated according to a standard protocol during two-lung ventilation and OLV. Fibre optic bronchoalveolar lavage (BAL) of the ventilated lung was performed before and after OLV and 2 h postoperatively. Alveolar cells, protein, tumour necrosis factor alpha (TNFalpha), interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM), IL10, and polymorphonuclear (PMN) elastase were determined in the BAL fluid. Data were analysed by parametric or non-parametric tests, as indicated. RESULTS: In both groups, an increase in pro-inflammatory markers was found after OLV and 2 h postoperatively; however, the fraction of alveolar granulocytes (median 63.7 vs 31.1%, P < 0.05) was significantly higher in the propofol group compared with the desflurane group. The time courses of alveolar elastase, IL-8, and IL-10 differed between groups, and alveolar TNFalpha (7.4 vs 3.1 pg ml(-1), P < 0.05) and sICAM-1 (52.3 vs 26.3 ng ml(-1), P < 0.05) were significantly higher in the propofol group. CONCLUSIONS: These data indicate that pro-inflammatory reactions during OLV were influenced by the type of general anaesthesia. Different patterns of alveolar cytokines may be a result of increased granulocyte recruitment during propofol anaesthesia.