Monica Franciosi

Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review.

Aims/Hypothesis Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes. Methods Data source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers. Results Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74–0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36–0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76–0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83–0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma. Conclusions/Interpretation Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.

Self-monitoring of blood glucose in non-insulin-treated diabetic patients: a longitudinal evaluation of its impact on metabolic control

Aims  In the framework of a nationwide outcomes research programme, we assessed the impact of self‐monitoring of blood glucose (SMBG) on metabolic control over 3 years in patients with Type 2 diabetes mellitus (DM2) not treated with insulin.

Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population

Objective: While many studies have shown an association between the gene coding for adiponectin (ADIPOQ) and adiponectin levels, much more controversy surrounds its association with metabolic traits such as insulin resistance, obesity and type 2 diabetes. Furthermore, very few studies have looked into the relations between ADIPOQ variants and risk of cardiovascular disease. The present study assessed the influence of four common ADIPOQ Single Nucleotide Polymorphisms (SNPs), rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T) on the risk of myocardial infarction and type 2 diabetes. Methods and Results: A large genetic association case-control study was conducted in 2008 Italians, including patients with myocardial infarction, type 2 diabetes, or both, and a reference group of healthy controls. Homozygotes TT for the rs1501299 (+276) had half the risk of either myocardial infarction alone or in association with type 2 diabetes when compared to the carriers of the G allele (OR = 0.58, p =0.01, and OR = 0.55, p =0.006 respectively). SNPs rs17300539 (-11391), rs266729 (-11377) and rs2241766 (+45) showed no significant association with any of the three case groups. Conclusions: These results suggest that homozygotes TT for the adiponectin polymorphism rs1501299 (+276) are protected from the risk of myocardial infarction.

Randomized Trial of 2 Versus 5 Years of Adjuvant Tamoxifen for Women Aged 50 Years or Older With Early Breast Cancer: Italian Interdisciplinary Group for Cancer Evaluation Study of Adjuvant Treatment in Breast Cancer 01

PURPOSE To compare 2 with 5 years of adjuvant tamoxifen therapy in the treatment of early breast cancer. PATIENTS AND METHODS Women with breast carcinoma T1-3, N0-3, M0, who were between 50 and 70 years of age, were eligible irrespective of menopausal status, tumor grade, or estrogen receptor (ER) status. Patients who were event-free after 2 years of tamoxifen therapy were randomly assigned to stop or continue tamoxifen therapy for an additional 3 years. The primary end point was length of disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. RESULTS From 1989 through 1996, 1,901 patients were randomly assigned either to stop treatment (n = 958) or to receive tamoxifen for 3 additional years (n = 943). The median duration of postrandomization follow-up was 52 months. We found no statistically significant differences between the 5-year arm and the 2-year arm in terms of DFS (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.76 to 1.08) and OS (HR, 1.16; 95% CI, 0.92 to 1.46). In ER-positive patients, a statistically significant prolongation of DFS related to longer treatment duration was observed (HR, 0.74; 95% CI, 0.59 to 0.93), whereas no difference in OS could be detected (HR, 0.98; 95% CI, 0.72 to 1.32). No differences in terms of endometrial cancers, cardiac or cerebrovascular events, or fractures were detected, whereas a doubling in the risk of thromboembolic events was found in the 5-year arm. CONCLUSION Our results confirm previous research that shows that 5 years of tamoxifen decreases recurrence compared to 2 years in patients with ER-positive tumors.

Identifying Patients at Risk for Microalbuminuria via Interaction of the Components of the Metabolic Syndrome: A Cross-Sectional Analytic Study

BACKGROUND AND OBJECTIVES The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated. RESULTS The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia < 140 mg/dl showed the lowest prevalence of microalbuminuria (1.9%) and represented the reference class. The likelihood of microalbuminuria was seven times higher in men with hypertension and homeostatic model assessment levels in the upper tertile and four times higher in women with the same characteristics. Individuals with hypertension and lower homeostatic model assessment levels and normotensive individuals with postload glycemia > or = 140 mg/dl had a more than three-fold increased likelihood of having microalbuminuria. Treatment with statins was associated with a 54% reduction in the likelihood of having microalbuminuria, whereas levels of triglycerides > 150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria. CONCLUSIONS The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.

Alternative site blood glucose testing: a multicenter study.

The aim of this study was to compare glucose measurements between fingertip and forearm using the blood glucose (BG) monitoring system One Touch Ultra (LifeScan), an electrochemical sensor that requires only a very small drop of blood (1 microL). Patients with type 1 or type 2 diabetes were identified in five outpatient diabetes clinics. Participants were requested to use the One Touch Ultra at home for 1 week for the measurement of BG levels from both sites. Patients filled in a questionnaire about their experience with testing blood samples from fingertip and forearm. The agreement between the measurements from the two sites was assessed using linear regression analysis, mean absolute relative error (MARE), the Bland-Altman method, and Error Grid Analysis (EGA). Overall, 112 patients were recruited, of whom 58% had type 1 diabetes. Linear regression analysis showed an intercept of 17.7, statistically different from 0 (p<0.0001). The slope was 0.956, and the Pearson correlation coefficient was 0.95. A MARE of 12.1% (SD=11.8%) was obtained, with a greater deviation of the forearm values from the fingertip ones in the hypoglycemic range (MARE=22.3%; SD=21.7%). The Bland-Altman bias plot showed a mean bias of 10.2 mg/dL (SD=23.1), with no correlation between mean difference and average BG levels (r=0.02). The EGA showed that 89.2% of the values fell in zone A, 10.4% in zone B, and 0.4% in zone C. The vast majority of patients (71%) declared that the collection of blood from the forearm caused no pain or less pain than the traditional site. Only 17% of the patients declared that it was impossible to obtain any blood from the forearm, while 63% reported with satisfaction that the quantity requested was small. At the end of the study period, 32% of the participants indicated the forearm as the preferred test site. Alternative site testing on the arm, with a BG meter that requires only a very small drop of blood, is feasible and reliable under routine clinical conditions. When testing with the express purpose of detecting hypoglycemia, the finger still remains the recommended test site.

Common genetic variants on chromosome 9p21 are associated with myocardial infarction and type 2 diabetes in an Italian population

BackgroundA genomic region on chromosome 9p21 has been identified as closely associated with increased susceptibility to coronary artery disease (CAD) and to type 2 diabetes (T2D) although the evidence suggests that the genetic variants within chromosome 9p21 that contribute to CAD are different from those that contribute to T2D.We carried out an association case-control study in an Italian population to test the association between two single nucleotide polymorphisms (SNPs) on the 9p21 locus, rs2891168 and rs10811661, previously reported by the PROCARDIS study, and respectively myocardial infarction (MI) and T2D. Our aim was to confirm the previous findings on a larger sample and to verify the independence of their susceptibility effects: rs2891168 associated with MI but not with T2D and rs10811661 associated with T2D but not with MI.MethodsGenomic DNA samples of 2407 Italians with T2D (602 patients), who had had a recent MI (600), or had both diseases (600) and healthy controls (605) were genotyped for the two SNPs. The genotypes were determined by allelic discrimination using a fluorescent-based TaqMan assay.ResultsSNP rs2891168 was associated with MI, but not with T2D and the G-allele odds ratio (OR) was 1.20 (95% CI 1.02-1.41); SNP rs10811661 was associated with T2D, but not with MI, and the T-allele OR was 1.27 (95% CI 1.04-1.55). ORs estimates from the present study and the PROCARDIS study were pooled and confirmed the previous findings, with greater precision.ConclusionsOur replication study showed that rs2891168 and rs10811661 are independently associated respectively with MI and T2D in an Italian population. Pooling our results with those reported by the PROCARDIS group, we also obtained a significant result of association with diabetes for rs10811661 in the European population.

Development and validation of a questionnaire evaluating the impact of hepatitis B immune globulin prophylaxis on the quality of life of liver transplant recipients.

To date, there is still a lack of instruments for specifically assessing the impact of anti–hepatitis B virus prophylaxis after liver transplantation (LT) on health‐related quality of life (HRQOL) and treatment satisfaction. Focusing on the use of hepatitis B immune globulin (HBIG), we developed and validated the Immunoglobulin Therapy After Liver Transplantation Questionnaire (ITaLi‐Q), which includes 41 items and covers 5 domains (side effects, positive and negative feelings, impact on the flexibility of daily activities, support, and satisfaction). The questionnaire was tested by 177 consecutive LT patients [71.8% were male, 38.4% were more than 60 years old, 58.8% were on intramuscular (IM) HBIG, and 41.2% were on intravenous (IV) HBIG]. A factor analysis confirmed the hypothesized structure, and a multitrait, multi‐item analysis showed favorable psychometric characteristics for ITaLi‐Q: item‐scale correlations > 0.40 for all items but 1, high scaling success rates (>90% for all scales but 1), excellent internal consistency (Cronbachs α ≥ 0.8 for all scales), and good reproducibility (test‐retest coefficient > 0.70 for all scales but 2). ITaLi‐Q was able to discriminate between subgroups of patients according to their clinical and sociodemographic characteristics. In comparison with patients on IV HBIG, patients on IM HBIG reported significantly better HRQOL scores on the Flexibility (81.5 ± 21.4 versus 73.1 ± 24.2, P = 0.01) and Negative Feelings scales (90.1 ± 17.3 versus 85.4 ± 20.7, P = 0.04), but they reported worse HRQOL scores on the Side Effects scale (81.8 ± 22.8 versus 95.6 ± 7.4, P < 0.001). No differences were found between the route of HBIG administration and the Satisfaction, Positive Feelings, Impact, and Support scales. In conclusion, ITaLi‐Q showed adequate psychometric characteristics and revealed that the route of HBIG administration has a significant impact on specific HRQOL domains beyond a patients satisfaction. Liver Transpl 18:332–339, 2012.

Subcutaneous hepatitis B immunoglobulin after liver transplantation. Reply

We are grateful to Yoshida et al. for their interest in our recent work on the development and validation of a questionnaire examining the quality of life (QOL) of liver transplantation (LT) recipients given long-term intravenous (IV) or intramuscular (IM) prophylaxis against hepatitis B virus. We share with these authors the view that the prevention of the posttransplant recurrence of hepatitis B virus should be based on a combination therapy using antiviral agents and hepatitis B immune globulins (HBIGs), and this strategy is almost universally used in our country. The questionnaire has been developed to capture patients’ feelings, needs, and perceived QOL when they are receiving HBIG because no specific instrument was previously available and because such issues are seldom taken into account when the route of HBIG administration is being chosen. However, we are especially appreciative of Yoshida et al.’s focus on the recent introduction of subcutaneous (SC) HBIG, which may further help to rekindle the issue of patients’ centeredness in the post-LT management algorithm. In their previous experience with switching from the IM route to the SC route, LT patients preferred the latter, mainly because there was less pain. However, this is only 1 element of the dimensions of primary relevance composing the QOL spectrum in patients receiving long-term treatment. Recently, a European experience using a specifically designed SC HBIG formulation was reported. Yahyazadeh et al. switched stable LT recipients from IV HBIG to SC HBIG with the primary goal of defining the efficacy and safety of the proposed innovative treatment. Interestingly, the authors reported that the majority of the patients were progressively able to selfadminister SC HBIG, and despite the lack of specific measurements, they speculated that self-administration was pivotal to improving QOL. Similarly, previous studies exploring the impact of the conversion from IV immune globulin to SC immune globulin in patients affected by primary immunodeficiency syndrome have shown relevant advantages in both QOL and costs. To better capture the complex interplay of treatment-related pain, self-management, the disruption of daily routines, and patient preferences, we felt that there was a need to design and validate a specific questionnaire for LT patients on HBIG. Our results show that the route of HBIG administration has a significant impact on specific QOL domains. We compared the IV route with the IM route because SC HBIG was not yet commercially available in our country at that time. However, with the completion of a national, multicenter, single-arm study of the feasibility and safety of switching from IV or IM HBIG to SC HBIG and with its recent approval for commercial use after LT, we are currently applying and validating the questionnaire in patients converted to SC HBIG in order to shed more light on the impact of the SC route on QOL domains.