David S. Lopez

Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies.

Objectives To summarise the evidence and evaluate the validity of the associations between type 2 diabetes and the risk of developing or dying from cancer. Design An umbrella review of the evidence across meta-analyses of observational studies of type 2 diabetes with risk of developing or dying from any cancer. Data sources PubMed, Embase, Cochrane database of systematic reviews, and manual screening of references. Eligibility criteria Meta-analyses or systematic reviews of observational studies in humans that examined the association between type 2 diabetes and risk of developing or dying from cancer. Results Eligible meta-analyses assessed associations between type 2 diabetes and risk of developing cancer in 20 sites and mortality for seven cancer sites. The summary random effects estimates were significant at P=0.05 in 20 meta-analyses (74%); and all reported increased risks of developing cancer for participants with versus without diabetes. Of the 27 meta-analyses, eventually only seven (26%) compiled evidence on more than 1000 cases, had significant summary associations at P≤0.001 for both random and fixed effects calculations, and had neither evidence of small study effects nor evidence for excess significance. Of those, only six (22%) did not have substantial heterogeneity (I2>75%), pertaining to associations between type 2 diabetes and risk of developing breast, cholangiocarcinoma (both intrahepatic and extrahepatic), colorectal, endometrial, and gallbladder cancer. The 95% prediction intervals excluded the null value for four of these associations (breast, intrahepatic cholangiocarcinoma, colorectal, and endometrial cancer). Conclusions Though type 2 diabetes has been extensively studied in relation to risk of developing cancer and cancer mortality and strong claims of significance exist for most of the studied associations, only a minority of these associations have robust supporting evidence without hints of bias.

Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial

OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence, but randomized controlled trials did not support this hypothesis. RESEARCH DESIGN AND METHODS A retrospective cohort study, Clinical Practice Research Datalink, was designed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial. A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis (initiators) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% CI. RESULTS A total of 51,484 individuals (54%) were metformin initiators and 18,264 (19%) were sulfonylurea initiators, and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years. Compared with initiators of sulfonylurea, initiators of metformin had a similar incidence of total cancer (HR 0.96; 95% CI 0.89–1.04) and colorectal (HR 0.92; 95% CI 0.76–1.13), prostate (HR 1.02; 95% CI 0.83–1.25), lung (HR 0.85; 95% CI 0.68–1.07), or postmenopausal breast (HR 1.03; 95% CI 0.82–1.31) cancer or any other cancer. CONCLUSIONS In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas.

Prostate cancer in Mexican‐Americans: Identification of risk factors

There is a paucity of information regarding prostate cancer (PCa) risk factors among Hispanics, the fastest‐growing ethnic group in the United States.

Association between endogenous sex steroid hormones and inflammatory biomarkers in US men

Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone‐binding globulin (SHBG) with biomarkers of inflammation, C‐reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999–2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, −0.18; p‐trend, 0.001) and calculated free (slope, −0.13; p‐trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (≤3.3 ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (≥3 mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00–2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p‐trend, <0.001; Free E2: slope, 0.15; p‐trend, <0.001) and WBC (Total E2: slope, 0.02; p‐trend, 0.08; Free E2: slope, 0.02; p‐trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, −0.03; p‐trend, 0.04), but not with CRP. These cross‐sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti‐inflammatory effect in men.

Parental history of stroke and myocardial infarction predicts coronary artery calcification: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

Background Few studies have examined the relationship between parental history of stroke and myocardial infarction (MI) and subclinical atherosclerosis, especially among young, asymptomatic individuals. This study investigates the association between coronary artery calcification (CAC) and parental history of stroke and MI in African-Americans and Caucasians from the CARDIA study. Methods Parental history of stroke and MI was determined by self-administered family history questionnaire at baseline and Year 5 examinations. Presence of coronary calcification was determined by computed tomography on 3041 individuals, age 32 to 47, including 1375 African-Americans and 1666 Caucasians. Analyses were restricted to individuals free of clinically manifest coronary heart disease (CHD) and stroke. Results Parental history of stroke is associated with a two-fold greater risk of CAC in African-Americans, and this relationship is independent from established CHD risk factors (95% CI = 1.14–3.43). There is no relationship between parental history of stroke and CAC status in Caucasians. Parental history of MI is associated with a two-fold greater risk of CAC in Caucasians (95% CI = 1.38–2.92). The impact of parental history of MI in African-Americans is lower (OR = 1.65; 95% CI = 1.01–2.69) and no longer statistically significant after adjusting for known CHD risk factors. Conclusions The identification of individuals with a parental history of stroke and MI provides important information for clinicians by which to target primary prevention efforts. Further characterization of familial factors, especially genetic factors, contributing to increased risk of CAC will shed light on the basis of the observed associations.

Parental history of stroke and myocardial infarction predicts coronary artery calcification

BACKGROUND Few studies have examined the relationship between parental history of stroke and myocardial infarction (MI) and subclinical atherosclerosis, especially among young, asymptomatic individuals. This study investigates the association between coronary artery calcification (CAC) and parental history of stroke and MI in African-Americans and Caucasians from the CARDIA study. METHODS Parental history of stroke and MI was determined by self-administered family history questionnaire at baseline and Year 5 examinations. Presence of coronary calcification was determined by computed tomography on 3041 individuals, age 32 to 47, including 1375 African-Americans and 1666 Caucasians. Analyses were restricted to individuals free of clinically manifest coronary heart disease (CHD) and stroke. RESULTS Parental history of stroke is associated with a two-fold greater risk of CAC in African-Americans, and this relationship is independent from established CHD risk factors (95% CI=1.14-3.43). There is no relationship between parental history of stroke and CAC status in Caucasians. Parental history of MI is associated with a two-fold greater risk of CAC in Caucasians (95% CI=1.38-2.92). The impact of parental history of MI in African-Americans is lower (OR=1.65; 95% CI=1.01-2.69) and no longer statistically significant after adjusting for known CHD risk factors. CONCLUSIONS The identification of individuals with a parental history of stroke and MI provides important information for clinicians by which to target primary prevention efforts. Further characterization of familial factors, especially genetic factors, contributing to increased risk of CAC will shed light on the basis of the observed associations.

Role of Caffeine Intake on Erectile Dysfunction in US Men: Results from NHANES 2001-2004

Objectives Caffeine is consumed by more than 85% of adults and little is known about its role on erectile dysfunction (ED) in population-based studies. We investigated the association of caffeine intake and caffeinated beverages with ED, and whether these associations vary among comorbidities for ED. Material and Method Data were analyzed for 3724 men (≥20 years old) who participated in the National Health and Nutrition Examination Survey (NHANES). ED was assessed by a single question during a self-paced, computer-assisted self-interview. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable logistic regression analyses using appropriate sampling weights were conducted. Results We found that men in the 3rd (85-170 mg/day) and 4th (171-303 mg/day) quintiles of caffeine intake were less likely to report ED compared to men in the lowest 1st quintile (0-7 mg/day) [OR: 0.58; 95% CI, 0.37–0.89; and OR: 0.61; 95% CI, 0.38–0.97, respectively], but no evidence for a trend. Similarly, among overweight/obese and hypertensive men, there was an inverse association between higher quintiles of caffeine intake and ED compared to men in the lowest 1st quintile, P≤0.05 for each quintile. However, only among men without diabetes we found a similar inverse association (Ptrend = 0.01). Conclusion Caffeine intake reduced the odds of prevalent ED, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive, but not among diabetic men. Yet, these associations are warranted to be investigated in prospective studies.

PROSTATE CANCER EDUCATION, DETECTION, AND FOLLOW-UP IN A COMMUNITY-BASED MULTIETHNIC COHORT OF MEDICALLY UNDERSERVED MEN

The Prostate Outreach Project (POP) provided free prostate cancer (PCa) education and early detection to medically underserved communities. POP recruited participants in medically underserved communities. PCa education and detection events occurred in POP locations (static) or natural gathering places (mobile) within the community. PCa education was delivered by video and evaluated using a questionnaire. Screening consisted of serum prostate-specific antigen and digital rectal examination. A navigated follow-up strategy was utilized to provide medical care for participants with abnormal screening examinations (ASE). POP recruited 4,420 men, 62.8% (2,667) were African American (AA). Most participants had a high school education and no prior screening. Fifty-four percent (2,159) were uninsured and 41% (1,811) had no access to a physician. PCa knowledge increased following the educational video. Prostate-specific antigen levels were elevated in 9.8% (436), while 6.9% (233) had an abnormal digital rectal examination. Follow-up among 609 men with ASE was successful in 40% (244), despite a navigated approach. Overall, 3.3% (144) cancers were diagnosed among the POP with AA participants exhibiting a significantly higher incidence. Recruitment, education, and PCa testing among a medically underserved cohort was successful. However, failure to follow through on ASE could contribute to maintaining the disparity in PCa outcomes noted among AAs and the medically underserved if not addressed.

Testosterone replacement therapy and the heart: Friend, foe or bystander?

The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, “beneficial (friendly use)”, “detrimental (foe)” and “no effects at all (bystander)”, based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT’s). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT’s does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

Double Trouble: co-occurrence of testosterone deficiency and body fatness associated with all-cause mortality in US men

Testosterone deficiency (TD, total testosterone ≤350 ng/dL [12.15 nmol L−1]) and obesity epidemic are growing in parallel in the United States. Yet, the sequelae of TD and obesity on the risk of mortality remain unclear.