Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study

Aims/hypothesis

The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk.

Methods

A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models.

Results

During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m² (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p _trend?<?0.0001 and p _trend?=?0.03, respectively). The NEAP score provided similar findings.

Conclusions/interpretation

We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.     

Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan

BACKGROUND: An association between diabetes mellitus (DM) and cancer has long been speculated, but no conclusive evidence has been obtained. METHODS: We prospectively examined the association between a history of DM and subsequent risk of cancer in the Japan Public Health Center-Based Prospective Study. A total of 97 771 general Japanese persons (46 548 men and 51 223 women) aged 40 to 69 years who responded to the baseline questionnaire, from January 1990 to December 1994, were followed up for cancer incidence through December 31, 2003. At baseline, 6.7% of men and 3.1% of women had a history of DM. RESULTS: A total of 6462 cases of newly diagnosed cancer were identified. In men, a 27% increase in the risk of total cancer incidence was observed in those with a history of DM (n = 3907 [366 with DM]; hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.14-1.42). The HR was especially high for those with cancer of the liver (n = 312 [52 with DM]; HR, 2.24; 95% CI, 1.64-3.04), pancreas (n = 118 [16 with DM]; HR, 1.85; 95% CI, 1.07-3.20), and kidney (n = 99 [13 with DM]; HR, 1.92; 95% CI, 1.06-3.46). We also observed a moderately increased risk of colon cancer (n = 491 [46 with DM]; HR, 1.36; 95% CI, 1.00-1.85) and of stomach cancer with borderline significance (n = 977 [87 with DM]; HR, 1.23; 95% CI, 0.98-1.54). In women, a borderline significant increase in risk was observed for the incidence of total cancer (n = 2555 [104 with DM]; HR, 1.21; 95% CI, 0.99-1.47), while statistical significance was observed for the incidence of stomach cancer (n = 362 [20 with DM]; HR, 1.61; 95% CI, 1.02-2.54) and liver cancer (n = 120 [10 with DM]; HR, 1.94; 95% CI, 1.00-3.73) and borderline significance was observed for the incidence of ovarian cancer (n = 74 [5 with DM]; HR, 2.42; 95% CI, 0.96-6.09). CONCLUSION: Patients with DM drawn from the general Japanese population may be at increased risk of total cancer and of cancer in specific sites.     

Prevalence and risk factors of hyperuricemia: results of the Kailuan cohort study

Objective: The objective of this study is to determine the serum uric acid (SUA) level and the prevalence of hyperuricemia (HUA) in Chinese population.

Methods: We conducted a cross-sectional study among 100,226 employees (79.9% male) of the Kailuan Group using physical examination data in 2006–2007. HUA was defined as SUA >356.9?μmol/L (6.0?mg/dL) for women and SUA >416.4?μmol/L (7.0?mg/dL) for men. We investigated crude and age adjusted HUA prevalence and compared characteristics of subjects with and without HUA in men and women using multivariate logistic regression.

Results: SUA levels were 244.9?±?71.5?μmol/L in women and 302.0?±?83.5?μmol/L in men. About 8290 (8.27%) subjects were diagnosed with HUA. Age-adjusted prevalence of HUA was 8.02% in the total sample (6.87% in women and 8.57% in men). The SUA level and HUA prevalence showed U-shaped or J-shaped associations with age. Multivariate logistic regression revealed age, waist circumference, total cholesterol, triglyceride, hypertension and non-alcoholic fatty liver disease history, prolonged sitting, alcohol consumption, and oral diuretics were independent risk factors of HUA, while long sleep duration was protective against HUA.

Conclusions: The prevalence of HUA is 6.87% and 8.57% in Chinese women and men. HUA is likely related with life style and metabolic disorders.     

Correlation of the dysmetabolic risk factors with different anthropometric measurements

Metabolic syndrome is a common disorder in Taiwan. For this study 431 subjects were randomly selected from visitors to the Department of Health Management. Blood pressure, blood glucose, lipid, uric acid levels and anthropometric measurements with immunoreactive insulin (IRI) and leptin levels were all correlated. We randomly selected 431 subjects who visited the Department of Health Management. Whole body three-dimensional (3-D) laser scanner scans were employed for the anthropometric measurements. The metabolic index (MI) was designed using anthropometric parameters. Of the 431 subjects, 50% had displayed a body mass index (BMI) equal to or exceeding 25 kg/m2. Pearson correlation coefficient and multiple regression analysis revealed that MI constituted another index for correlating metabolic parameters by comparing MI with BMI and waist circumference to hip circumference ratio (WHR). Most data related to metabolic syndrome showed statistically significant differences between high and low IRI groups, comprising uric acid, total cholesterol, fasting plasma glucose, triglyceride, LDL, Chol/HDL ratio, and LDL/HDL ratio. Both IRI and leptin revealed statistical association with BMI, WHR, waist cross section area to hip cross section area ratio (WHAR), and MI in the study. Hypercholesterolemia appeared in 14.6% of the subjects. Elevated low-density lipoprotein (> or = 130 mg/dL) affected 36.9% of the subjects. In conclusion, MI calculated from 3-D body scanner correlated with many important metabolic risk factors and associated with clinical disorders like DM, hyperlipidemia, hyperuricemia and hypertension.     

Candida infection and cancer risk: A Danish nationwide cohort study

BackgroundCandida species infection may be associated with increased cancer risk.MethodsWe linked data from the nationwide medical registries and examined the incidence of various cancers in patients with a first-time hospital presentation with candida infection. We computed the cumulative incidence of cancer and standardized incidence ratios (SIRs) of cancer overall, immune-related cancers, and specific cancer types by comparing observed versus expected incidences based on age-, sex-, and anatomical site-specific incidence rates.ResultsAmong 21,247 candida-infected patients, we identified 1534 cancers during a combined follow-up of 187,993 years (standardized incidence ratio (SIR) = 1.6 (95% confidence interval (CI): 1.5–1.7)). The 1- and 10-year risks of cancer were 2.6%, and 8.3%, respectively. In the first year after a candida diagnosis, the SIR for cancer was 3.7 (95% CI: 3.4–4.0). In the second and subsequent years of follow-up, the SIRs were 1.2 (95% CI: 1.1–1.3) for any cancer and 1.4 (95% CI 1.2–1.7) for immune-related cancers. The risk of mouth and throat cancers remained more than 3-fold increased in the second and subsequent years of follow-up.ConclusionsHospital presentation with candida infection is associated with increased short- and long-term cancer risk.     

Juvenile idiopathic arthritis and risk of cancer: A nationwide cohort study

Objective

Reports of therapy‐related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population.

Methods

Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969–2007 and specialist outpatient visits in 2001–2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics‐naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available.

Results

In this biologics‐naive JIA cohort, 60 malignancies were observed during 131,144 person‐years of followup, compared with 266 cancers observed during 661,758 person‐years in the general population comparator (0.46 cases/1,000 person‐years versus 0.40 cases/1,000 person‐years; RR 1.1, 95% confidence interval [95% CI] 0.9–1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7–10.7) and cancers overall (RR 2.3, 95% CI 1.2–4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity.

Conclusion

Although absolute risks were low, an elevated risk of malignancy was observed among biologics‐naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.

     

Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1)

Abstract. Thomas J‐A II, Gerber L, Moreira DM, Hamilton RJ, Bañez LL, Castro‐Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan‐Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston‐Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272 : 85–92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5–10.0 ng mL^?1 and a negative prestudy biopsy. Among men undergoing at least one on‐study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22–1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73–1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38–2.15) (P‐interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72–3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84–1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.     

Computed tomography scans of intra-abdominal fat, anthropometric measurements, and 3 nonobese metabolic risk factors

The present cross-sectional study of 46 adult Danish white men and women aimed to evaluate association between intra-abdominal obesity, 4 anthropometric measurements of obesity, and combinations of 3 nonobese metabolic risk factors: systolic blood pressure of 130 mm Hg or higher, serum triglyceride concentration of more than 1.7 mmol/L, and fasting capillary blood glucose concentration of 5.6 mmol/L or more. For 80% of the subjects, intra-abdominal fat on a computed tomography scan of the abdomen using a cutoff limit of more than 144 cm(2) gave a correct classification of combinations of at least 2 of the 3 metabolic risk factors. Body mass index and waist circumference were better markers of intra-abdominal obesity than waist-to-hip ratio in receiver operating characteristic analyses (P = .0035). Body mass index of more than 26 kg/m(2) and waist circumference of more than 0.92 m classified 76% and 74% of the subjects correctly regarding combinations of the 3 nonobese metabolic risk factors. Intra-abdominal obesity was significantly stronger associated with the combinations than a raised waist-to-hip ratio (P = .016). Both body mass index and waist circumference may be used as markers of intra-abdominal obesity, whereas waist-to-hip ratio was significantly inferior. Correspondingly, both body mass index and waist circumference were better than waist-to-hip ratio to indicate combinations of the 3 nonobese metabolic risk factors.     

Hypertension and breast cancer risk in a 19-year follow-up study (the DOM cohort). Diagnostic investigation into mammarian cancer

BACKGROUND: To investigate whether hypertension and the use of anti-hypertensive drugs are associated with breast cancer risk. METHODS: This was a prospective study of 11, 011 women living in Utrecht, the Netherlands, aged 50-65 years at enrolment in a breast cancer screening project (DOM cohort). Women attended screening rounds between 1974 and 1985 at which blood pressure was measured and information on drug use and breast cancer risk factors was ascertained. Since 1974 (median follow-up time 19 years), information on breast cancer occurrence and death has been registered. Hypertension was defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 95 mmHg or current use of drugs for the indication hypertension. Cox's regression analysis was used to investigate the association between hypertension (treated or untreated) and subsequent breast cancer risk. Analyses were adjusted for age, body mass index, height, parity, familial breast cancer, smoking and oral contraceptive use. RESULTS: A total of 523 women were diagnosed with breast cancer. Hypertensive women experienced a statistically significant increased breast cancer risk of 23% (age-adjusted hazard ratio (HRa) = 1.23; 95% confidence interval (CI) 1.01 -1.49). After adjustment for all confounders, the increase was 14% (HR = 1.14; 95% CI 0.93-1.40). The decline in risk was mainly attributable to the effect of BMI. The risk was similar in treated (HR = 1.22; 95% CI 0.91-1.63) and untreated hypertensive women (HR = 1.13; 95% CI 0.91-1.40). CONCLUSION: These results do not support an association between hypertension and breast cancer, and if there is a link, it is likely to be positive and relatively small in size (+14%). This relation, if present, is not attributable to anti-hypertensive drugs, since the relation is also present in non-drug users.