Hospitalisation for herpes zoster in people with and without diabetes: A 10-year-observational study.

AIMS: This study explores the association between Herpes Zoster (HZ) hospitalizations and diabetes in Piedmont, Italy from 2010 to 2019. Focusing on the burden of HZ hospitalizations in diabetic and non-diabetic groups, it aims to identify risk factors in diabetics to enhance prevention strategies. METHODS: In a two-phase study, we first compared age-standardized HZ hospitalization rates between diabetic and non-diabetic individuals from 2010 to 2019. We then examined hospitalization risk factors for HZ within a diabetic patient cohort managed by regional diabetes clinics. RESULTS: Of 3,423 HZ hospitalizations in 2010-2019, 17.9 % (613 cases) were diabetic patients, who exhibited higher hospitalization rates (15.9 to 6.0 per 100,000) compared to non-diabetese individuals. Among diabetics subjects risk factors for HZ hospitalization included age over 65, obesity (BMI > 30), and poor glycemic control (HbA1c > 8.0 %). These patients had a 40 % increased rehospitalization risk and a 25 % higher risk of severe complications, such as stroke and myocardial infarction, post-HZ. CONCLUSIONS: Diabetes markedly increases HZ hospitalization rates, rehospitalization, and complication risks. These findings underscore the need for preventive strategies, especially improved glycemic control among high-risk diabetic patients, to inform public health policies and clinical practices aimed at mitigating HZ's impact on this population.

Hepatocellular carcinoma in a large cohort of type 2 diabetes patients.

AIMS: To elucidate the current burden of hepatocellular carcinoma (HCC) in type 2 diabetes (DM2) with a focus on the associated clinical determinants. METHODS: Incidence of HCC between 2009 and 2019 in the diabetic and general population was calculated from regional administrative and hospital databases. Potential determinants of the disease were evaluated with a follow-up study. RESULTS: In the DM2 population, the incidence resulted in 8.05 cases per 10,000 yearly. This rate was three times higher than that of the general population. 137,158 patients with DM2 and 902 HCC were found for the cohort study. The survival of HCC patients was 1/3 of that of cancer-free diabetic controls. Age, male sex, alcohol abuse, previous viral hepatitis B and C, cirrhosis, low platelet count, elevated GGT/ALT, higher BMI and HbA1c levels were associated with HCC occurrence. Diabetes therapy was not adversely associated with HCC development. CONCLUSION: Incidence of HCC in DM2 is more than tripled compared to the general population with high mortality. These figures are higher than those expected from the previous evidence. In parallel with known risk factors for liver disease, such as viruses and alcohol, insulin-resistance characteristics are associated with a higher probability of HCC.

Hepatic fibrosis of any origin in a large population of type 2 diabetes patients.

BACKGROUND AND AIMS: Excess morbidity and mortality from chronic liver disease in type 2 diabetes (T2DM) is recognized; however, the clinical features associated with liver fibrosis (LF) of any origin are poorly known. Metabolic status and/or coexisting complications over time may play a role. METHODS AND RESULTS: We interrogated the database of the diabetes unit network of Piedmont (Italy) (71,285 T2DM patients) and calculated a fibrosis-4 score (FIB-4) from data recorded between 2006 and 2019. Comorbidities were obtained by linkage with hospital data. The study population was subdivided by aetiology of LF (alcoholic, viral, metabolic). Associations between upper level of FIB-4 and demographic and clinical variables were evaluated separately for each group using robust Poisson models and presented as prevalence ratios. Nearly one-quarter (24%) of T2DM patients had some form of LF: viral (0.44%) and alcoholic (0.53%) forms were far less frequent than metabolic ones (22.7%). Only 1 out of 5 of these patients had a history of known cirrhosis. Age, male sex, duration of diabetes, coronary disease, hyperuricemia, renal failure, and features of liver failure (e.g., lower body-mass index, lipid and HbA1c levels) were positively associated with metabolic LF. More intensive treatments with insulin and segretagogue emerged as a significant predictive indicators of LF of metabolic origin. CONCLUSION: A sizeable proportion of T2DM patients has some degree of LF, mainly of metabolic origin and often undiagnosed. There is a need to clarify whether the link between insulin therapy and advanced LF is causal or not.

Incretin-based therapy and risk of cholangiocarcinoma: a nested case-control study in a population of subjects with type 2 diabetes.

BACKGROUND AND AIMS: One cohort and several basic science studies have raised suspicion about an association between incretin therapies and cholangiocarcinoma. Our aim was to verify the occurrence of CC in relation to incretin-based medication use versus any antidiabetic treatment in an unselected population of diabetic patients. METHODS: A population-based matched case-control study was conducted using administrative data from the Region of Piedmont (4,400,000 inhabitants), Italy. From a database of 312,323 patients treated with antidiabetic drugs, we identified 744 cases hospitalized for cholangiocarcinoma from 2010 to 2016 and 2976 controls matched for gender, age and initiation of antidiabetic therapy; cases and controls were compared for exposure to incretin-based medications. All analyses were adjusted for risk factors for CC, as ascertained by hospital discharge records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fitting a conditional logistic model. RESULTS: The mean age of the sampled population (cases and controls, 75 years) was very high, with no gender prevalence. Five per cent was treated with incretin-based medications. After adjusting for possible confounders, we found no increased risk of cholangiocarcinoma associated with the use of either DPP4i (OR 0.98, 95% CI 0.75-1.29: p = 0.89) or GLP-1-RA (OR 1.09, 95% CI 0.63-1.89; p = 0.76) in the 24 months before hospital admission. Neither the duration of the therapy nor the dose modified the risk of cholangiocarcinoma. CONCLUSIONS: Our findings suggest that, in an unselected population, the use of both classes of incretin-based medications is not associated with an increased risk of cholangiocarcinoma.

Impact of severe and symptomatic hypoglycemia on quality of life and fear of hypoglycemia in type 1 and type 2 diabetes. Results of the Hypos-1 observational study.

BACKGROUND AND AIMS: Hypoglycemia represents a relevant burden in people with diabetes. Consequences of hypoglycemia/fear of hypoglycemia on quality of life (QoL) and behaviors of patients with T1DM and T2DM were assessed. METHODS AND RESULTS: HYPOS-1 was an observational retrospective study. Fear of hypoglycemia (Fear of Hypoglycemia Questionnaire, FHQ), general health status (visual analog scale of EuroQol questionnaire, EQ5D-VAS) psychological well-being (WHO-5 well being index, WHO-5), diabetes related distress (Problem Areas in Diabetes 5, PAID-5), and corrective/preventive behaviors following hypoglycemia were compared between people with and without previous experience of severe and symptomatic hypoglycemia and by tertiles of FHQ scores. A multivariate analysis was performed to identify factors associated with the likelihood of being in the third tertile of FHQ score. Overall, 2229 patients were involved. Severe hypoglycemia had statistically significant and clinically relevant (measured as effect sizes) negative impact on EQ5D-VAS, WHO-5, PAID-5, and FHQ both in T1DM and T2DM. In T2DM, symptomatic episodes had similar impact of severe hypoglycemia. Moving from the first to the third FHQ tertile, lower scores of EQ-5D VAS and WHO-5, and higher levels of PAID-5 were found. Patients in the third tertile performed more frequently corrective/preventive actions that negatively impact on metabolic control. Previous hypoglycemia, insulin treatment, female gender, age, and school education were the independent factors associated with increased likelihood to be in the third tertile. CONCLUSION: Not only severe but also symptomatic hypoglycemia negatively affect patient QoL, especially in T2DM. Addressing fear of hypoglycemia should be a goal of diabetes education.

Cardiovascular Effects of Pioglitazone or Sulfonylureas According to Pretreatment Risk: Moving Toward Personalized Care.

CONTEXT: Hypoglycemic drugs with proven cardiovascular (CV) benefits are recommended for patients with type 2 diabetes and CV disease. Whether the beneficial effects extend to those at lower risk remains unclear. AIM: We investigated the long-term CV effects of pioglitazone or sulfonylureas (SUs) across the spectrum of pretreatment CV risk. METHODS: Among 2820 participants of the TOSCA.IT trial, four subgroups with different risk of outcome-a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, urgent coronary revascularization-were identified by the RECursive Partitioning and AMalgamation (RECPAM) method. Within each group, the effect of SUs or pioglitazone on the outcome was evaluated. RESULTS: Sex was the first splitting variable, followed by urinary albumin-to-creatinine ratio (UACR) (>9 mg/g or ≤9 mg/g) and body mass index (BMI) (>28.7 or ≤28.7 kg/m2). Female patients had the lowest risk (reference); male patients with UACR >9 mg/g and BMI >28.7 kg/m2 had the highest risk [hazard ratio (HR), 5.58; 95% CI, 3.32 to 9.69]. Patients in this group present a cluster of conditions suggestive of marked insulin resistance (higher BMI, waist circumference, triglycerides, blood pressure, and UACR and lower high-density lipoprotein cholesterol) than the other groups. Treatment with pioglitazone in this group was associated with a significantly lower occurrence of the outcome than SUs (HR, 0.48; 95% CI, 0.25 to 0.76). No significant difference between study treatments was observed in the other RECPAM classes. CONCLUSIONS: It is possible to identify patients with type 2 diabetes early in the stage of their disease and who are largely free from evident CV disease in whom add-on pioglitazone to metformin confers CV protection as compared with SUs.

Beta cell stress in a 4-year follow-up of patients with type 2 diabetes: A longitudinal analysis of the BetaDecline Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a progressive deterioration in beta cell function and loss of glycaemic control. Clinical predictors of beta cell failure are needed to guide appropriate therapy. METHODS: A prospective evaluation of a large set of potential predictors of beta cell stress, measured as change in the proinsulin/insulin (PI/I) ratio, was conducted in a cohort of 235 outpatients with T2DM on stable treatment with oral hypoglycaemic agents or diet followed up for ~4 years (median value 3.9 years; interquartile range 3.8-4.1 years). RESULTS: Overall, metabolic control deteriorated over time, with a significant increase in glycated haemoglobin (HbA1c; P < .0001), proinsulin (P < .0001), and PI/I ratio (P = .001), without significant changes in the homeostatic model assessment of insulin resistance. Multivariate regression analysis showed that for each 1% (10.9 mmol/mol) increase from baseline in HbA1c, the risk of beta cell stress increased by 3.8 times; for each 1% (10.9 mmol/mol) incremental increase in HbA1c during the study, risk of beta cell stress increased by 2.25 times that at baseline. By contrast, baseline anthropometric and clinical variables, lipid profile, inflammatory markers (PCR, IL-6), non-esterified fatty acids, and current therapies did not independently influence PI/I ratio variation during follow-up. CONCLUSIONS: In this cohort of patients with T2DM, beta cell function progressively deteriorated despite current therapies. Among a large set of clinical and biochemical predictors, only baseline HbA1c levels and their deterioration overtime were associated with higher beta cell stress over time.

Portrait of women with type 1 or type 2 diabetes of childbearing age attending diabetes clinics in Italy: the AMD-Annals initiative.

AIM: To describe characteristics relevant in case of an unplanned pregnancy for T1D or T2D women of childbearing age. METHODS: We analyzed the 2011 AMD-Annals dataset, compiling information from 300 clinics (28,840 T1D patients and 532,651 T2D patients). A risk score of unfavorable conditions for pregnancy included HbA1c > 8.0%; BMI ≥ 35; systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg; microalbuminuria/proteinuria; use of statins, ACE inhibitors, ARB; use of diabetes drugs other than metformin/insulin. RESULTS: The proportion of T2D cases increased from 30.8% (95% CI 29.9-32.4) at age 18-30 years to 67.5% (66.6-68.5) at age 36-45 years. The proportion of women with HbA1c < 7.0% was 20.4% (20.0-20.8) in T1D and 43.4% (42.8-43.9) in T2D women. Furthermore, 47.6% (47.0-48.3) of T1D women and 34.5% (33.9-35.0) of T2D women had HbA1c ≥ 8.0%. The prevalence of obesity (BMI ≥ 30) was sevenfold higher among T2D than T1D women [49.9% (49.4-50.5) and 7.4% (7.2-7.5), respectively]. T2D women were more likely to have hypertension or microalbuminuria than T1D women. Almost half of the T2D women were taking drugs not approved during pregnancy. At least one unfavorable condition for starting a pregnancy was present in 51% of T1D women of childbearing age and in 66.7% of T2D women. CONCLUSIONS: Women with either T1D or T2D of childbearing age in Italy were far from the ideal medical condition for conception. Our data strongly support the need for counseling all women with diabetes about pregnancy planning.

Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial.

BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.

Prevalence, incidence and associated comorbidities of treated hypothyroidism: an update from a European population.

OBJECTIVE: Estimates of the prevalence of hypothyroidism in unselected populations date from the late 1990s. We present an update on the prevalence and incidence of overt hypothyroidism in Piedmont, northwest Italy and examine the association between hypothyroidism and multiple chronic comorbidities. DESIGN AND METHODS: Data were obtained from drug prescription and hospital discharge databases. Individuals who had received at least two levothyroxine prescriptions in 2012 were defined as having hypothyroidism; those who had undergone thyroidectomy or I131 irradiation in the previous 5 years were defined as having iatrogenic hypothyroidism and those who had either obtained exemption from treatment co-payment or had been discharged from hospital with a chronic comorbidity (diabetes and connective tissue diseases) were identified as having one of these conditions. RESULTS: The overall crude prevalence was 31.1/1000 (2.3/1000 for iatrogenic hypothyroidism) and the overall crude incidence was 7/1000. The average daily dose of thyroxine (122 µg) roughly corresponded to 1.7 µg/kg. There was a strong association between hypothyroidism and diabetes (type 1, type 2 or gestational) and with autoimmune diseases, with the odds ratio ranging from 1.43 (1.02-1.99) for psoriatic arthritis to 4.99 (3.06-8.15) for lupus erythematosus. CONCLUSIONS: As compared with previous estimates, the prevalence of hypothyroidism rose by about 35%, driven mainly by non-iatrogenic forms. The increase may be due to either population aging or improved diagnostic capability or both. The frequent co-occurrence of hypothyroidism with other multiple chronic conditions characterizes it more as a comorbidity rather than an isolated chronic disease.

Polyphenol intake and cardiovascular risk factors in a population with type 2 diabetes: The TOSCA.IT study.

BACKGROUND: The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. AIM: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. METHODS: Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. RESULTS: Average intake of polyphenols was 683.3 ± 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. CONCLUSIONS: Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. CLINICAL TRIAL: http://www.clinicaltrials.gov; Study ID number: NCT00700856.

Sexual Dysfunction in Type 2 Diabetes at Diagnosis: Progression over Time and Drug and Non-Drug Correlated Factors.

AIMS: To present the longitudinal data of the SUBITO-DE study, a prospective survey involving male patients with new or recently diagnosed type 2 diabetes mellitus (T2DM) (<24 months). MATERIALS AND METHODS: Sexual function was assessed in male patients with T2DM at baseline (phase 1) and after a mean follow-up of 18 months (phase 2). Standard metabolic parameters and sexual and depressive symptoms were evaluated. RESULTS: Six of the 499 enrolled patients died of different causes during phase 1. Of the 493 surviving men invited to participate in phase 2, 450 (mean age 59.0±9.0 years) (90.2%) accepted and 43 (8.2%) were lost to follow-up. As compared to baseline, the proportion of the men who reported improvement in erectile dysfunction (ED) at follow-up was nearly double that of the men who reported worsening of ED (22.6% vs. 12.8%). The increase in frequency of sexual activity the men reported at follow-up assessment indicates that many never treated before baseline were taking an ED drug during the study period (106 subjects). Phosphodiesterase type 5 inhibitors (PDE5i) were the ED drugs most commonly taken at both baseline and follow-up. An overall improvement over baseline values was observed in metabolic targets for T2DM and depressive symptoms. Conversely, no change in lifestyle behaviors was recorded during the study. CONCLUSIONS: Sexual dysfunction is a major concern in men with T2DM. The SUBITO-DE study demonstrates that, when combined with adequate counseling and tailored PDE5i therapy, an integrated approach to achieving metabolic targets in men with T2DM can improve sexual function as well as depressive symptoms.

Incidence and correlated factors of beta cell failure in a 4-year follow-up of patients with type 2 diabetes: a longitudinal analysis of the BETADECLINE study.

AIMS: Type 2 diabetes is associated with progressive deterioration of beta cell function and loss of glycemic control, with increased morbidity and mortality from microvascular and macrovascular complications. Factors predictive of beta cell decline are needed. METHODS: We have conducted a prospective evaluation of baseline predictors of beta cell dysfunction and insulin initiation in a cohort of outpatients with type 2 diabetes receiving stable treatment with oral hypoglycemic agents or dietary intervention, over a 4-year follow-up period. RESULTS: Of 507 patients enrolled, 56 (10.8 %) experienced the study endpoint of initiation of insulin therapy. Univariate and multivariate Cox proportional hazard regression analyses revealed that the likelihood of initiating insulin therapy during follow-up increased with longer diabetes duration and with higher baseline values for hemoglobin A1c, fasting plasma glucose, triglycerides, proinsulin, interleukin-6, Homeostatic Model Assessment-IR and lower values for Homeostatic Model Assessment-B. The likelihood of initiating insulin therapy increased by 46 % for each 1 % increase (10.9 mmol/mol) in baseline hemoglobin A1c and by 6 % for each unit increase (1 ng/l) in baseline IL-6 level. The risk was fourfold higher in the lowest versus highest Homeostatic Model Assessment-B quartile. Treatment with metformin plus a secretagogue increased the risk by fourfold. CONCLUSIONS: Our results show that commonly measured parameters may predict treatment failure in type 2 diabetes and suggest that early treatment with metformin plus secretagogues may foretell this failure.

Results of the Adequacy of glycemiC Control in pAtients with type 2 Diabetes mEllitus treated with Metformin monotherapY at the maximal-tolerated dose (ACCADEMY) study.

The treatment objective in diabetes is prevention of the onset or progression of complications. Intensive treatment reduces the risk of complications. The aim of the study was to evaluate glycemic control in patients with type 2 diabetes mellitus treated with metformin monotherapy at the maximal-tolerated dose. This retrospective, multicenter, observational study, enrolled patients ≥45-year old receiving metformin as monotherapy for at least 36 months. Data were collected on demographic and disease characteristics, clinical status, lifestyle, comorbidities, and diabetes complications at baseline, 9, 18, and 24 months. Primary study variables were percentage of patients achieving HbA1c <7 % and mean HbA1c reduction after 9 months. Eligible patients (n = 524, mean age 65.9 ± 7.9 years) had a mean age at diagnosis of 57.5 ± 7.9 years. A second antidiabetic drug was added in 24 % of patients (126/524); time to treatment escalation was 44.7 ± 25.1 months. Regarding primary study variables, 61.7 % of patients (322/522) achieved HbA1c of 7.0 % at 9 months, compared to 37.0 % of patients (194/524) at baseline; mean HbA1c was reduced from 7.30 ± 0.95 to 6.84 ± 0.86 % after 9 months. The estimated mean time of exposure above 7 % was 19 months, 15 months for patients ≥65-year old, and 21 months for younger patients. Regression analysis revealed that patients with longer disease duration, and patients <65-year old responded less well to metformin. A substantial number of patients continued to receive monotherapy instead of intensified therapy and were exposed to hyperglycemia.

Hospitalisation for heart failure and mortality associated with dipeptidyl peptidase 4 (DPP-4) inhibitor use in an unselected population of subjects with type 2 diabetes: a nested case-control study.

OBJECTIVE: The SAVOR TIMI-53 study reported a significant increase in the risk of hospitalisation for heart failure (HF) in patients treated with a DPP-4 inhibitor (DPP-4i) in comparison with placebo. A recent case-control study in part confirmed this risk signal. Our aim was to compare the occurrence of HF in relation to DPP-4i use versus any antidiabetic treatment. DESIGN: Population-based matched case-control study conducted using administrative data. SETTING: The Italian Region of Piedmont (4.4 million inhabitants). PARTICIPANTS: From a database of 282,000 patients treated with antidiabetic drugs, we identified 14,613 hospitalisations for HF, 7212 incident cases, and 1727 hospital re-admissions between 2008 and 2012; each case was matched for gender, age and antidiabetic therapy with 10 controls; cases and controls were compared for exposure to DPP-4i. OUTCOME MEASURES: ORs and 95% CIs were calculated by fitting a conditional logistic model. All analyses were adjusted for available risk factors for HF. RESULTS: We found no increased risk of hospitalisation for HF associated with the use of DPP-4i (OR for admission for HF 1.00 (0.94 to 1.07), incident HF1.01 (0.92 to 1.11), recurrent HF 1.02 (0.84 to 1.22)). All-cause mortality was 6% lower in DPP-4i users (p<0.001), whereas insulin users showed an excess of risk for any type of hospital admission (19%) and death (20%) (p<0.001). CONCLUSIONS: Our findings suggest that, in an unselected population of diabetic patients, the use of DPP-4i is not associated with an increased risk of HF. The favourable impact on all-cause mortality should be viewed with caution and also other explanations investigated.

Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study.

OBJECTIVE: Hypoglycemia is common in type 1 diabetes mellitus (T1DM). We aimed to update the incidence of severe and symptomatic hypoglycemia and investigate several correlated factors. METHODS: In this multicenter, observational retrospective study, the data of 206 T1DM patients from a sample of 2,229 consecutive patients seen at 18 diabetes clinics were analyzed. Sociodemographic and clinical characteristics, severe hypoglycemia in the past 12 months, and symptomatic hypoglycemia in the past 4 weeks were recorded with a self-report questionnaire and a clinical form during a routine visit. Poisson multivariate models were applied. RESULTS: A minority of patients accounted for the majority of both severe and symptomatic episodes. The incidence rate (IR) of severe hypoglycemia was 0.49 (0.40-0.60) events/person-years. The incidence rate ratio (IRR) was higher in patients with previous severe hypoglycemia (3.71; 2.28-6.04), neuropathy (4.16; 2.14-8.05), long duration (>20 years, 2.96; 1.60-5.45), and on polypharmacy (1.24; 1.13-1.36), but it was lower when a complication was present. The IR of symptomatic hypoglycemia was 53.3 events/person-years, with an IRR significantly higher among women or patients with better education, or shorter duration or on pumps. The IRR was lower in patients with higher BMI or neuropathy or aged more than 50 years. CONCLUSIONS: Fewer than 20 % of T1DM patients are free from hypoglycemia, with one in six having experienced at least one severe episode in the last year. The distribution is uneven, with a tendency of episodes to cluster in some patients. Severe and symptomatic episodes have different correlates and reflect different conditions.

Incretin-based therapies and acute pancreatitis risk: a systematic review and meta-analysis of observational studies.

Concerns raised by several animal studies, case reports, and pharmacovigilance warnings over incretin-based therapy potentially exposing type two diabetes patients to an elevated risk of pancreatitis have cast a shadow on the overall safety of this class of drugs. This systematic review evaluates the data from observational studies that compared treatment with or without incretins and the risk of pancreatitis. We searched PubMed for publications with the key terms incretins or GLP-1 receptor agonists or DPP-4 inhibitors or sitagliptin or vildagliptin or saxagliptin or linagliptin or alogliptin or exenatide or liraglutide AND pancreatitis in the title or abstract. Studies were evaluated against the following criteria: design (either cohort or case-control); outcome definition (incidence of pancreatitis); exposure definition (new or current or past incretins users); and comparison between patients receiving incretins or not for type 2 diabetes. Two authors independently selected the studies and extracted the data. Six studies meeting the inclusion criteria were reviewed. No difference was found in the overall risk of pancreatitis between incretin users and non-users (odds ratio 1.08; 95 % CI [0.84-1.40]). A risk increase lower than 35 % cannot be excluded according to the power calculation. This systematic review and meta-analysis suggests that type 2 diabetes patients receiving incretin-based therapy are not exposed to an elevated risk of pancreatitis. Limitations of this analysis are the low prevalence of incretin users and the lack of a clear distinction by the studies between therapy with DPP-4 inhibitors or with GLP-1 receptor agonists.

Sexual dysfunction at the onset of type 2 diabetes: the interplay of depression, hormonal and cardiovascular factors.

INTRODUCTION: Several data have emphasized the importance of early diagnosis of erectile dysfunction (ED) and meticulous cardiovascular investigation in the type 2 diabetic mellitus (T2DM) patients. AIM: To estimate the prevalence of ED and its associated determinants in a sample of male patients with new or recently diagnosed T2DM. METHODS: The SUBITO-DE study is an observational, multicenter, prospective study involving 27 Italian diabetes centers. Male patients recently diagnosed with T2DM were consecutively interviewed by their attending physician at the diabetes care centers and asked whether they had experienced a change in their sexual function or found it unsatisfactory. Those responding positively were then invited to participate in the study. MAIN OUTCOME MEASURE: Several hormonal and biochemical parameters were studied. RESULTS: A nonselected series of 1,503 patients was interviewed, 499 of which (mean age, 58.8 ± 8.8 years) entered the study, yielding a final enrolment rate of 33.3%. ED was classified as mild in 19.4%, mild-to-moderate in 15.4%, moderate in 10.4%, and severe in 21.6% of patients, respectively. In addition, premature ejaculation, delayed ejaculation, and hypoactive sexual desire (HSD) were comorbid in 28.3%, 32.9%, and 58.4%, respectively. Finally, hypogonadism, showed an estimated prevalence of almost 20%. Both organic (at least one chronic DM-associated complication) and psychological factors (severe depressive symptoms) increased the risk of ED. Severe depressive symptoms were also associated with ejaculatory problems, HSD, and hypogonadism. CONCLUSIONS: A high prevalence of sexual dysfunction in men with recently diagnosed T2DM was detected. Early diagnosis of ED could help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of sexual dysfunction should become a part of routine care in the management of T2DM patients.

Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study.

BACKGROUND: Previous studies have yielded conflicting results about the association between incretin therapies and acute pancreatitis. We aimed to compare the occurrence of acute pancreatitis in a population of patients with type 2 diabetes who received incretins compared with those who received other antidiabetic treatment. METHODS: In our population-based matched case-control study, we extracted information from an administrative database from Piedmont, Italy (containing data for 4·4 million inhabitants). From a dataset of 282,429 patients receiving treatment with antidiabetic drugs for type 2 diabetes, we identified 1003 cases older than 41 years who had been admitted to hospital for acute pancreatitis between Jan 1, 2008, and Dec 31, 2012, and 4012 controls who were matched for sex, age, and time of start of antidiabetic therapy. We compared incretin exposure in cases and controls with a conditional logistic regression model, expressed as odds ratios (ORs [95% CI]). We adjusted all analyses for risk factors of acute pancreatitis, as ascertained by hospital discharge records, and concomitant use of metformin or glibenclamide. FINDINGS: The mean age of cases and controls (72·2 years [SD 11·1]) was high, as expected in an unselected diabetic population in Europe. After adjustment for available confounders, use of incretins in the 6 months before hospital admission was not associated with increased risk of acute pancreatitis (OR 0·98, 95% CI 0·69-1·38; p=0·8958). INTERPRETATION: Our findings suggest that, in an unselected population, use of incretins is not associated with an increased risk of acute pancreatitis. Larger studies are needed to clarify whether age or type of incretin therapy could affect the risk of acute pancreatitis in patients with type 2 diabetes. FUNDING: Chaira Medica Association, Chieri, Italy.