Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) e waist body mass index (wBMI): Which is better?

Obesity and overfat are most commonly assessed using the body mass index (BMI), which evaluates "total obesity", without accounting for body fat distribution. Therefore, several indexes of obesity have been proposed, combining BMI with other measures or singular parameters. The aim of the study was to evaluate the accuracy of a new, simple index that takes into account both BMI and Waist Circumference (WC), Waist Body Mass Index (wBMI) in comparison to BMI, WC e Waist-to-Height Ratio (WHtR) for the identification of overfat and obese patients identified by fat mass percentage (FM%). 2400 non diabetic patients were enrolled. From the analysis carried out it emerges that wBMI, BMI, WC and WHtR all have a statistically significant positive correlation (p-Value < 0.001) with FM%. The multivariate analysis showed the positive relationship between these four indexes and the FM. To assess the accuracy of these indices in diagnosing the condition of overfat and obesity we used the statistical analysis Receiver Operating Characteristic (ROC). The Area Under the Curve (AUC) derived from the ROC showed that for the male gender the indicator with the greatest discriminating capacity of the conditions of overfat and obesity was the WHtR and the wBMI for the female gender. The wBMI is therefore configured as an additional tool at the disposal of the healthcare professional aimed at framing the overfat and obese patient and monitoring him during the course of treatment. Moreover wBMI is an indicator able to provide information about the FM% constituting an accurate tool for the evaluation of the overfat and obese patient.

Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: In our previous works, we demonstrated that patients' sex affects the efficacy of immune checkpoint inhibitors (ICIs) in patients with several advanced solid tumors. Here, we assessed the sex-based heterogeneity of efficacy of anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) given as monotherapy, for advanced non-small-cell lung cancer (NSCLC) expressing high PD-L1 levels, to evaluate if available evidence supports this therapeutic option for both women and men. METHODS: We carried out a systematic review and meta-analysis including all randomized, controlled trials testing anti-PD-1/anti-PD-L1 drugs in monotherapy, as first-line treatment of advanced NSCLC expressing high PD-L1 levels. The primary endpoint was the difference in efficacy of anti-PD-1/anti-PD-L1 drugs versus chemotherapy, between men and women, measured in terms of the difference in overall survival (OS) log [hazard ratio (HR)] reported in male and female study participants. RESULTS: We analyzed four randomized, controlled trials, including 1672 patients, of whom 1224 (73.2%) were men and 448 (26.8%) were women. The pooled OS-HR comparing anti-PD-1/anti-PD-L1 versus chemotherapy was 0.59 [95% confidence interval (CI), 0.50-0.69] for men and only 0.84 (95% CI, 0.64-1.10) for women. The pooled ratio of the OS-HRs reported in men versus women was 0.71 (95% CI, 0.52-0.98; P-heterogeneity: 0.04), indicating a significantly greater effect for men. No heterogeneity among single-study estimates was observed in either male patients (Q = 2.39, P = 0.50, I2 = 0%) or in female patients (Q = 1.13, P = 0.50, I2 = 0%). CONCLUSION: Evidence available indicates anti-PD-1/anti-PD-L1 monotherapy as highly effective in men but not in women, even in NSCLCs expressing high PD-L1 levels. Prospective trials testing sex-based tailored immunotherapy strategies are needed.

Thymic carcinoma with Lynch syndrome or microsatellite instability, a rare entity responsive to immunotherapy.

IMPORTANCE: Thymic carcinoma (TC) is a rare aggressive tumour occurring in adults characterised by one of the lowest tumor mutational burdens (TMB). Microsatellite instability (MSI) is a mutational signature, caused by defects in the DNA MisMatch Repair (MMR) system, that predicts benefit from immunotherapy and causes high TMB. Fragmentary and unstructured evidence of these conditions co-occurring are reported in literature. OBJECTIVE: Review available data on the co-occurrence of these two conditions and determine its frequency in our institute case series. DESIGN: We performed a systematic analysis of literature and a retrospective evaluation of all the cases of TET treated at our institution from 2000 to 2020, selecting patients with a medical history of multiple tumours to enhance a priori probability of identifying cases with underlying predisposition. RESULTS: Literature yielded 3 cases of patients with MSI TC, for which MMR gene alteration was reported. None of them received immunotherapy. Of 366 patients with TETs treated in our institute, 32 had a medical history of multiple tumours and 25 of 32 (19 thymomas and 6 TCs) had available tissue for MMR analysis. One patient with TC showed a high TMB, and MSI due to MLH1 mutation and was treated in a phase II study with avelumab and axitinib combination obtaining a long-lasting partial response. MLH1 alterations are shared across MSI TC cases. CONCLUSIONS AND RELEVANCE: This analysis highlights the usefulness of MSI testing in patients with TC. The observation of cases of TC occurring in patients with Lynch syndrome and the unexpected homogeneity of gene alterations support further investigation.

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).

The Italian Association of Medical Oncology recommendations on thymic epithelial tumors, which have been drawn up for the first time in 2020 through an evidence-based approach, report indications on all the main aspects of clinical management of this group of rare diseases, from diagnosis and staging, to new available systemic treatments, such as targeted therapies and immunotherapies. A summary of key recommendations is presented here and complete recommendations are reported as Supplementary Materials, available at https://doi.org/10.1016/j.esmoop.2021.100188.

Effects of real-time continuous glucose monitoring in type 1 diabetes: a meta-analysis of randomized controlled trials.

AIMS: Self-monitoring of blood glucose (SMBG) represented a major breakthrough in the treatment of type 1 diabetes. The aim of the present meta-analysis is to assess the effect of continues glucose monitoring (CGM) and flash glucose monitoring (FGM), on glycemic control in type 1 diabetes. MATERIALS AND METHODS: The present analysis includes randomized clinical trials comparing CGM or FGM with SMBG, with a duration of at least 12 weeks, identified in Medline or clinicaltrials.gov. The principal endpoint was HbA1c at the end of the trial. A secondary endpoint was severe hypoglycemia. Mean and 95% confidence intervals for HbA1c and Mantel-Haenzel odds ratio [MH-OR] for severe hypoglycemia were calculated, using random effect models. A sensitivity analysis was performed using fixed effect models. In addition, the following secondary endpoints were explored, using the same methods: time in range, health-related quality of life, and treatment satisfaction. Separate analyses were performed for trials comparing CGM with SMBG, and those comparing CGM + CSII and SMBG + MDI and CGM-regulated insulin infusion system (CRIS) and CSII + SMBG. RESULTS: CGM was associated with a significantly lower HbA1c at endpoint in comparison with SMBG (- 0.24 [- 0.34, - 0.13]%); CGM was associated with a significantly lower risk of severe hypoglycemia than SMBG. Treatment satisfaction and quality of life were not measured, or not reported, in the majority of studies. FGM showed a significant reduction in the incidence of mild hypoglycemia and an increased treatment satisfaction, but no significant results are shown in HbA1c. CGM + CSII in comparison with SMBG + MDI was associated with a significant reduction in HbA1c. Only two trials with a duration of at least 12 weeks compared a CRIS with SMBG + CSII; HbA1c between the two treatment arms was not statistically significant (difference in means: - 0.23 [- 0.91; 0.46]%; p = 0.52). CONCLUSION: GCM compared to SMBG has showed a reduction in HbA1c and severe hypoglycemia in patient with type 1 diabetes. The comparison between CGM + CSII and SMBG + MDI showed a large reduction in HbA1c; it is conceivable that the effects of CSII + CGM on glycemic control additives. The only comparison available between FGM and SMBG was conducted in patients in good control.

Baseline neutrophil-to-lymphocyte ratio (NLR) is associated with outcome of patients treated with BRAF inhibitors.

PURPOSE: The aim of this study is to verify if baseline hematological markers, in patients with advanced melanoma receiving BRAF inhibitor (BRAFi)-based therapies, are independently associated with progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed 90 patients with metastatic melanoma harboring BRAF V600 mutation, who received treatment with either BRAFi alone or combined with a MEK inhibitor (MEKi) at the recommended dosages. Study population included 28 women and 62 men. Median age was 53 years. Seventy-three (82%) patients presented with M1c disease, 49 (56%) had elevated LDH and 54 (60%) had three or more metastatic sites. RESULTS: The median PFS was 9.1 and 3.5 months, respectively, for patients with baseline NLR < 5 and NLR ≥ 5, while median OS was 17.2 and 5.5 months, respectively, for patients with NLR < 5 and NLR ≥ 5. Multivariate analysis confirmed that baseline NLR < 5 was significantly associated with half risk of relapse (HR = 0.49; 95% CI = 0.28-0.85; p = 0.01) and half risk of death (HR = 0.46; 95% CI = 0.23-0.76; p = 0.004), independent of age, sex, stage, LDH > 2xULN, previous treatments, concomitant use of steroids and type of therapy. In patients with LDH ≥ ULN, NLR < 5 remained significantly and independently associated with improved PFS (HR = 0.28; 95% CI = 0.13-0.62; p = 0.002,) and OS (HR = 0.23; 95% CI = 0.10-0.55; p = 0.001). CONCLUSIONS: These biomarkers are easily reproducible, affordable and costless and NLR could help to identify patients who have the best benefit from BRAF inhibitors.

Adjustment of insulin doses when switching from glargine 100 U/ml or detemir to degludec: an observational study.

BACKGROUND: Degludec is a long-acting insulin with a longer duration of action and a greater day-to-day reproducibility of absorption in comparison with previous long-acting insulin formulations. The aim is the definition of the change in insulin needs in patients switching from detemir/glargine to degludec in real-life conditions. METHODS: In this retrospective cohort observational study, all outpatients with either type 1 or type 2 diabetes, starting therapy with degludec insulin-after a prior treatment with either detemir or glargine insulin for at least 6 months-were included. RESULTS: The analysis was performed on 266 patients, 172 and 96 with type 1 and type 2 diabetes, respectively. The equations describing the relationship between baseline and follow-up doses of basal insulin (6 months) were Y = 3.39 + 0.78X and Y = 0.44 + 0.69X, in patients receiving detemir/glargine either once or twice daily, respectively (Y = degludec dose at 6 months and X = basal insulin dose at switch). The corresponding equations for prandial insulin doses were y = 1.83 + 0.83*x and y = 2.85 + 0.80*x for those on pre-switch once or twice-daily basal insulin, respectively. In type 2 diabetes, the switch was associated with a reduction of basal insulin doses only in those with a prior twice-daily treatment with basal insulin. The reduction of prandial insulin reached statistical significance only in patients previously treated with basal insulin once daily. CONCLUSIONS: The present results provide a suggestion for a simple method for the adjustment of basal and prandial insulin doses in type 1 diabetic patients, switching from glargine or detemir to degludec.

Introducing 12 new dyes for use with oligonucleotide functionalised silver nanoparticles for DNA detection with SERS.

Oligonucleotide functionalised metallic nanoparticles (MNPs) have been shown to be an effective tool in the detection of disease-specific DNA and have been employed in a number of diagnostic assays. The MNPs are also capable of facilitating surface enhanced Raman scattering (SERS) enabling detection to become highly sensitive. Herein we demonstrate the expansion of the range of specific SERS-active oligonucleotide MNPs through the use of 12 new Raman-active monomethine and trimethine chalcogenopyrylium and benzochalcogenopyrylium derivatives. This has resulted in an increased ability to carry out multiplexed analysis beyond the current small pool of resonant and non-resonant Raman active molecules, that have been used with oligonucleotide functionalised nanoparticles. Each dye examined here contains a variation of sulphur and selenium atoms in the heterocyclic core, together with phenyl, 2-thienyl, or 2-selenophenyl substituents on the 2,2',6, and 6' positions of the chalcogenopyrylium dyes and 2 and 2' positions of the benzochalcogenopyrylium dyes. The intensity of SERS obtained from each dye upon conjugate hybridisation with a complementary single stranded piece of DNA was explored. Differing concentrations of each dye (1000, 3000, 5000 and 7000 equivalents per NP-DNA conjugate) were used to understand the effects of Raman reporter coating on the overall Raman intensity. It was discovered that dye concentration did not affect the target/control ratio, which remained relatively constant throughout and that a lower concentration of Raman reporter was favourable in order to avoid NP instability. A relationship between the dye structure and SERS intensity was discovered, leaving scope for future development of specific dyes containing substituents favourable for discrimination in a multiplex by SERS. Methine dyes containing S and Se in the backbone and at least 2 phenyls as substituents give the highest SERS signal following DNA-induced aggregation. Principal component analysis (PCA) was performed on the data to show differentiation between the dye classes and highlight possible future multiplexing capabilities of the 12 investigated dyes.

Dabrafenib in metastatic melanoma: a monocentric 'real life' experience.

Dabrafenib is a potent BRAF-kinase inhibitor. Its activity was evaluated on 40 consecutive metastatic melanoma patients (pts) harboring the V600BRAF mutations. Dabrafenib was administered orally at the dosage of 150 mg b.i.d. daily. ORR was 82%, with 7% CR, 62% PR, 13% SD and 18% PD. The median PFS and OS were seven and 17 months, respectively (median follow-up: 8.5 months). Increased risk of progression was found in pts with elevated LDH, ECOG PS >1 and more than two metastatic sites. Grade 3-4 adverse events were recorded in 4 pts. In this retrospective analysis, Dabrafenib confirmed its role as the standard clinical option in metastatic melanoma pts.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

The role of DPP4 activity in cardiovascular districts: in vivo and in vitro evidence.

The introduction of incretin hormone-based therapies represents a novel therapeutic strategy, since these drugs not only improve glycemia with minimal risk of hypoglycemia, but also have other extraglycemic beneficial effects. These agents, which are effective in improving glucose control, could also have positive effects on the incidence of cardiovascular events. The aim of this review is to summarize the present literature about the role of dipeptidyl peptidase 4 (DPP4) in cardiovascular districts, not only strictly correlated to its effect on glucagon-like peptide-1 (GLP-1) circulating levels, but also to what is known about possible cardiovascular actions. Actually, DPP4 is known to be present in many cells and tissues and its effects go beyond purely metabolic aspects. Almost always the inhibition of DPP4 activity is associated with improved cardiovascular profile, but it has shown to possess antithrombotic properties and these different effects could be connected with a site and/or species specificity of DPP4. Certainly, DPP4 seems to exert many functions, both directly and indirectly, on cardiovascular districts, opening new possibilities of prevention and treatment of complications at this level, not only in patients affected by diabetes mellitus.

Effects of antihypertensive treatments on incidence of diabetes: a case-control study.

AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.

Hypertriglyceridaemic waist phenotype and ß-cell function in subjects with normal and impaired glucose tolerance.

AIM: To determine the association between the hypertriglyceridaemic waist phenotype, a combination of enlarged waist circumference and increased triglyceride levels, and ß-cell function in subjects with normal glucose tolerance and those with impaired glucose tolerance. METHODS: We studied 1344 outpatients clinic without diabetes. Overnight fasting blood samples were obtained to measure plasma glucose, insulin and lipids. An oral glucose tolerance test was performed in all subjects. All patients were divided in four groups, two groups with normal glucose tolerance and two with impaired glucose tolerance, with or without the hypertriglyceridaemic waist phenotype. Insulin resistance and ß-cell function were calculated by homeostatsis model assessment 2 indices. RESULTS: Twenty per cent of subjects showed the hypertriglyceridaemic waist phenotype and 23.8% had impaired glucose tolerance. We found a progressive significant increase (P < 0.001) of insulin resistance from subjects with normal glucose tolerance without the hypertriglyceridaemic waist phenotype with respect to patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype. In subjects with normal glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with a mild, but not significant, increase of homeostatsis model assessment 2-ß levels; but, in patients with impaired glucose tolerance, the hypertriglyceridaemic waist phenotype was associated with significantly lower homeostatsis model assessment 2-ß levels [127.0 (103.0-162.7) vs. 123.0 (96.0-147.0); P < 0.05]. The hypertriglyceridaemic waist phenotype displayed a higher (odds ratio 95% CI) ß-cell dysfunction of 1.8 (1.3-2.6) and insulin resistance of 5.0 (2.7-8.5) compared with 1.3 (0.9-1.9) and 2.4 (1.8-3.2), respectively, of waist circumference alone. CONCLUSION: In this study, the hypertriglyceridaemic waist phenotype is associated with increased insulin resistance and an overstimulation of ß-cell function in subjects with normal glucose tolerance, while patients with impaired glucose tolerance with the hypertriglyceridaemic waist phenotype showed a reduction in ß-cell function. These data suggest the importance of the identification of patients with impaired glucose tolerance combined with the hypertriglyceridaemic waist phenotype for an early intervention in relation to the high risk of developing Type 2 diabetes.

Motivational readiness for treatment in weight control programs: the TREatment MOtivation and REadiness (TRE-MORE) test.

BACKGROUND AND AIMS: The degree of motivation before starting the treatment represents a pre-treatment predictor of successful weight management. The aim of this study is to develop and validate a new self-reported questionnaire of motivation and readiness to change before starting a lifestyle modification program (the TREatment MOtivation and REadiness test) (TRE-MORE) for overweight patients. METHODS AND RESULTS: TRE-MORE was evaluated in a consecutive series of 129 obese patients attending our Outpatient Clinic. Validation of the questionnaire was performed through test-retest reliability, internal consistency, psychopathological correlates, and concurrent validity. Subjects have been evaluated by means of a clinical interview, and different self-reported questionnaires, assessing the eating specific and general psychopathology, and quality of life. TRE-MORE total and subscales scores showed good test-retest reliability and internal consistency. We identified 10 items grouped in 3 areas (obstacles and desire to overcome, taking care of themselves, and sharing the problems, current lifestyle). TREMORE scores were significantly correlated with eating specific psychopathology and quality of life measures. Univariate and Receiver Operating Characteristic curve analysis showed that TRE-MORE total and subscales scores represent a good model for predicting a weight loss >5% of the initial weight after 6 months of treatment. CONCLUSION: TRE-MORE represents a validated and easy-to-use questionnaire assessing at the meantime the treatment motivation and readiness with good predictive capacity for weight loss.

Relationship between GLP-1 levels and dipeptidyl peptidase-4 activity in different glucose tolerance conditions.

AIM: The reduced levels of glucagon-like peptide 1 (GLP-1) after an oral glucose load in Type 2 diabetic patients could be dependent either on a reduced synthesis or an increased degradation; but GLP-1 and dipeptidyl peptidase IV (DPP-IV) levels during an oral glucose tolerance test (OGTT) have not been studied together. The aim of the present study was to investigate GLP-1 and DPP-IV levels during an OGTT in patients with different degrees of glucose tolerance. METHODS: Fifty six subjects (34 female, 22 male) matched for sex, age, body mass index (BMI) and waist circumference underwent a 75 g oral glucose tolerance test. Twenty-eight had normal glucose tolerance, 15 had impaired glucose tolerance and 13 had Type 2 diabetes mellitus. GLP-1 assay was performed with an ELISA kit, and DPP-IV assay using a colorimetric method. RESULTS: At 30 min GLP-1 levels were significantly lower in subjects with impaired glucose tolerance and type 2 diabetes mellitus compared to those with normal glucose tolerance. The area under the GLP-1 curve was significantly different among the three groups; there was a significant decrease between subjects with normal and impaired glucose tolerance(P = 0.004) and between those with normal glucose tolerance and type 2 diabetes mellitus. (P < 0.001), while the area under the curve for DPP-IV showed no significant difference between the groups. CONCLUSIONS: These results suggest that an increase of GLP-1 degradation does not play a role in the early stages of diabetes mellitus.

Glucagon-like peptide-1 response to meals and post-prandial hyperglycemia in Type 2 diabetic patients.

BACKGROUND: The impaired response of glucagonlike peptide-1 (GLP-1) to meals in diabetic patients can contribute to the pathogenesis of impaired insulin secretion and post-prandial hyperglycemia. This study is aimed at the assessment of the relationship between meal-induced GLP-1 and post-prandial hyperglycemia in Type 2 diabetic patients. METHODS: Twenty-one drug-naïve Type 2 diabetic patients were studied. Blood glucose and active GLP-1 levels were measured 0, 30, 60, 90, and 120 min after a standard test meal. A continuous glucose monitoring (CGM) system was applied for the following 3 days. Nutrient intake at each meal was calculated on the basis of patients' food records. For each patient, post-prandial 120-min glucose incremental area under the curve (iAUC) was included in linear regression model exploring its relationship with total energy and carbohydrate intake, and the angular coefficient for total energy (EAC) and carbohydrate (CAC) was calculated. RESULTS: GLP-1 levels peaked 30 min after the test meal. Logarithmically transformed 60-min GLP-1 iAUC showed a significant inverse correlation with glycated hemoglobin (HbA1c) (p<0.01). A significant inverse correlation of 60-min GLP-1 iAUC was also observed with EAC and CAC (both p<0.01), meaning that patients with a lower GLP-1 response to the test meal had a higher increment of post-prandial glucose for each additional unit of total energy or carbohydrate intake. CONCLUSIONS: In Type 2 diabetic patients, a lower GLP-1 response to meals is associated with a higher HbA1c, and with a greater degree of meal-induced hyperglycemia, both in a meal test and during CGM in "real-life" conditions.

Treatment with insulin secretagogues and cancer-related mortality in type 2 diabetic patients a retrospective cohort study.

BACKGROUND: Recent evidence suggests that some hypoglycemic treatments could affect the incidence of malignancies. This study was aimed at the assessment of cancer-related mortality in type 2 diabetic patients treated with different hypoglycemic drugs. METHODS: A retrospective observational cohort study was performed on a consecutive series of 3002 type 2 diabetic outpatients. Cancer-related death was identified through the City Registry Office. For patients visited for the first time after January 1 (st), 2000, information on incidence of cancer was also available. RESULTS: During a mean follow-up of 4.3+/-2.5 years, 87 cases of cancer-related death were recorded, with a yearly incidence rate of 0.70%. Patients receiving secretagogues showed a significantly higher mortality than the rest of the sample (unadjusted OR [95%CI] 1.76 [1.15-2.69], p=0.009), which was maintained after adjustment for confounders (HR 2.29 [1.21-4.02], p=0.003). Conversely, no significant association of cancer-related mortality was observed with insulin sensitizers or exogenous insulin. In comparison with patients receiving no hypoglycemic treatment, those on secretagogue or insulin monotherapy showed a higher cancer-related mortality (HR 2.25 [1.10-4.78], p=0.034 and HR 2.11 [1.01-4.50], p=0.048, respectively). The effect of treatments on incidence of malignancies was similar to that observed on cancer-related death. CONCLUSIONS: Insulin secretagogues and, to a lesser extent, exogenous insulin, appear to be associated with increased mortality for cancer, even after adjustment for multiple confounders. This issue deserves further investigation through epidemiological studies on larger samples of patients.