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.

From swab testing to health outcomes within the T2DM population: Impact of diabetes background on COVID19 progression.

BACKGROUND: We aimed to study the impact of diabetes background on COVID-19 progression from swab testing to health outcomes in type 2 diabetes (T2DM). METHODS: From the database of the diabetes units of Piedmont-Italy we extracted records of T2DM patients, which were linked with the swab-testing-database, and the database of hospital discharges. Five outcomes (PCR testing, PCR testing positivity, hospitalization, Intensive Care Unit (ICU), death) were evaluated using robust Poisson models. RESULTS: Among 125,021 T2DM patients, 1882 had a positive PCR test. Of these patients, 49.4% were hospitalized within 30 days, 11.8% were admitted to an ICU, and 27.1% died. Greater probability of death was associated with age, male sex, liver and renal impairment, Hba1c above 8%, and former smoking. Hospitalization and ICU admission were mainly affected by age, male sex, hypertension, and metabolic control. Notably, ICU admissions were reduced in very elderly people. No outcomes were associated with educational level. CONCLUSIONS: Hospitalization and ICU admission are heavily affected by age and local triage policy. A key finding was that men who were > 75 years old and poorly compensated were highly vulnerable patients. Renal and/or hepatic impairment are additional factors. This information may be useful for addressing intervention priorities.

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.

Normoalbuminuric kidney impairment in patients with T1DM: insights from annals initiative.

BACKGROUND: We described, in a large sample of patients with type 1 diabetes mellitus (T1DM) and GFR ≤ 60 mL/min/1.73 m2 (with or without albuminuria), the differences in the clinical features associated with the two different chronic kidney disease phenotypes and we investigated, in a subset of patients, the modulating role of albuminuria on kidney disease progression. METHODS: Clinical data of 1395 patients with T1DM were extracted from electronic medical records. RESULTS: Albuminuria was detected in 676 (48.5%) patients, with the remaining 719 (51.5%) patients having normoalbuminuric renal impairment. Those with albuminuria showed an evident worse cardiovascular risk profile as compared to patients with normoalbuminuria. A subgroup of 582 patients was followed up over a 4-year period. One hundred and twenty five patients (21.5%) showed a loss of eGFR > 30%. The proportion of patients reaching the renal outcome was significantly higher among those with baseline albuminuria as compared to patients with normoalbuminuria (P < 0.0001). At the multivariate logistic analysis microalbuminuria, macroalbuminuria and proliferative retinopathy were the only parameters independently associated to eGFR reduction. CONCLUSIONS: The proportion of T1DM patients with normoalbuminuria renal impairment is high (about 50%). These patients have a slower eGFR decline as compared to that observed in patients with albuminuria renal impairment.

Diabetic kidney disease in the elderly: prevalence and clinical correlates.

BACKGROUND: Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, < 60 mL/min/1.73 m2) and albuminuria (Alb+) are essential for the diagnosis of DKD, but their association with clinical variables and quality of care may be influenced by ageing. METHODS: Here we investigated the association of clinical variables and quality of care measures with eGFR+ and Alb+ in 157,595 T2DM individuals participating to the Italian Association of Clinical Diabetologists (AMD) Annals Initiative, stratified by age. RESULTS: The prevalence of eGFR+ and Alb+ increased with ageing, although this increment was more pronounced for low eGFR. Irrespective of age, both the eGFR+ and Alb + groups had the worst risk factors profile when compared to subjects without renal disease, showing a higher prevalence of out-of target values of HbA1c, BMI, triglycerides, HDL-C, blood pressure and more complex cardiovascular (CVD) and anti-diabetic therapies, including a larger use of insulin In all age groups, these associations differed according to the specific renal outcome examined: male sex and smoking were positively associated with Alb+ and negatively with eGFR+; age and anti-hypertensive therapies were more strongly associated with eGFR+, glucose control with Alb+, whereas BMI, and lipid-related variables with both abnormalities. All these associations were attenuated in the older (> 75 years) as compared to the younger groups (< 65 years; 65-75 years), and they were confirmed by multivariate analysis. Notably, Q-score values < 15, indicating a low quality of care, were strongly associated with Alb+ (OR 8.54; P < 0.001), but not with eGFR+. CONCLUSIONS: In T2DM patients, the prevalence of both eGFR and Albuminuria increase with age. DKD is associated with poor cardiovascular risk profile and a lower quality of care, although these associations are influenced by the type of renal abnormality and by ageing. These data indicate that clinical surveillance of DKD should not be unerestimated in old T2DM patients.

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.

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.

Epidemiology of diabetic kidney disease in adult patients with type 1 diabetes in Italy: The AMD-Annals initiative.

BACKGROUND: Patients with type 1 diabetes mellitus are at increased risk of death. This risk appears to be modulated by kidney dysfunction. The aim of this study was to evaluate the prevalence of diabetic kidney disease (DKD), its traits, and clinical correlates in a large sample of patients with type 1 diabetes. METHODS: Clinical data of 20 464 patients with type 1 diabetes were extracted from electronic medical records. Estimated glomerular filtration rate (eGFR) and increased urinary albumin excretion were considered. RESULTS: Mean age of the patients was 46 ± 16 years, 55.0% were males, and duration of diabetes 19 ± 13 years. The frequency of diabetic kidney disease, low eGFR, and albuminuria was 23.5%, 8.1%, and 19.5%, respectively. In the multivariate analysis the presence of diabetic kidney disease was associated with age (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.10-1.18), duration of diabetes (OR = 1.05, 95% CI: 1.03-1.07), and worse glycemic control (OR = 1.24, 95% CI: 1.21-1.28, for every 1% glycated hemoglobin increase). Diabetic kidney disease was also independently associated with an atherogenic lipid profile and increased systolic blood pressure. Glucose control, systolic blood pressure, triglycerides, and high density lipoprotein cholesterol were associated with both low eGFR and albuminuria. Male gender, retinopathy and smoke were related to albuminuria, being female was related to low eGFR, while SUA levels were associated with DKD, low eGFR and albuminuria. CONCLUSIONS: In our sample of patients with type 1 diabetes, diabetic kidney disease entails an unsafe cardiovascular risk profile. Hyperglycemia, arterial hypertension, and atherogenic lipid profile affected both low eGFR and albuminuria. Retinopathy and smoking were related only to albuminuria while being female and elevated serum uric acid were associated only with low eGFR.

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.

Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement : Diabetes mellitus and thyroid disorders: recommendations for clinical practice.

Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management.

Left ventricular dysfunction and outcome at two-year follow-up in patients with type 2 diabetes: The DYDA study.

AIMS: Left ventricular dysfunction (LVD) in type 2 diabetes mellitus (DM) (DYDA) study is a prospective investigation enrolling 960 with DM without overt cardiac disease. At baseline, a high prevalence of LVD was detected by analysing midwall shortening. We report here the incidence of clinical events in DYDA patients after 2-year follow-up and the frequency of LVD detected at baseline and 2-year evaluation. METHODS: Systolic LVD was defined as midwall shortening ≤15%, diastolic LVD as any condition different from "normal diastolic function" identified as E/A ratio on Doppler mitral flow between 0.75 and 1.5 and deceleration time of E wave >140 ms. Major outcome was a composite of major events, including all-causes death and hospital admissions. RESULTS: During the study period, any systolic/diastolic LVD was found in 616 of 699 patients (88.1%) in whom LVD function could be measured at baseline or at 2 years. Older age and high HbA1c predicted the occurrence of LVD. During the follow-up 15 patients died (1.6%), 3 for cardiovascular causes, 139 were hospitalized (14.5%, 43 of them for cardiovascular causes, 20 for a new cancer). CONCLUSIONS: During a 2-year follow-up any LVD is detectable in a large majority of patients with DM without overt cardiac disease. Older age and higher HbA1c predict LVD. All-cause death or hospitalization occurred in 15% of patients, cardiovascular cause was uncommon. Independent predictors of events were older age, pathologic lipid profile, high HbA1c, claudicatio and repaglinide therapy. Echo-assessed LVD at baseline was not prognosticator of events.

The impact of adherence to screening guidelines and of diabetes clinics referral on morbidity and mortality in diabetes.

Despite the heightened awareness of diabetes as a major health problem, evidence on the impact of assistance and organizational factors, as well as of adherence to recommended care guidelines, on morbidity and mortality in diabetes is scanty. We identified diabetic residents in Torino, Italy, as of 1st January 2002, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations to compare primary versus specialty care management of diabetes and the fulfillment of a quality-of-care indicator based on existing screening guidelines (GCI). Then, we performed regression analyses to identify associations of these factors with mortality and cardiovascular morbidity over a 4 year-follow-up. Patients with the lowest degree of quality of care (i.e. only cared for by primary care and with no fulfillment of GCI) had worse RRs for all-cause (1.72 [95% CI 1.57-1.89]), cardiovascular (1.74 [95% CI 1.50-2.01]) and cancer (1.35 [95% CI 1.14-1.61]) mortality, compared with those with the highest quality of care. They also showed increased RRs for incidence of major cardiovascular events up to 2.03 (95% CI 1.26-3.28) for lower extremity amputations. Receiving specialist care itself increased survival, but was far more effective when combined with the fulfillment of GCI. Throughout the whole set of analysis, implementation of guidelines emerged as a strong modifier of prognosis. We conclude that management of diabetic patients with a pathway based on both primary and specialist care is associated with a favorable impact on all-cause mortality and CV incidence, provided that guidelines are implemented.

Recurrence of cardiovascular events in patients with type 2 diabetes: epidemiology and risk factors.

OBJECTIVE: The purpose of this study was to assess incidence of and risk factors for recurrent cardiovascular disease (CVD) in type 2 diabetes. RESEARCH DESIGN AND METHODS: We estimated the incidence of recurrent cardiovascular events in type 2 diabetic patients, aged 40-97 years, followed by a network of diabetes clinics. The analysis was conducted separately for 2,788 patients with CVD at enrollment (cohort A) and for 844 patients developing the first episode during the observation period (cohort B). RESULTS: During 4 years of follow-up, in cohort A the age-adjusted incidence of a recurrent event (per 1,000 person-years) was 72.7 (95% CI 58.3-87.1) in men and 32.5 (21.2-43.7) in women, whereas in cohort B it was 40.1 (17.4-62.9) in men and 22.4 (12.9-32.0) in women. After controls were included for potential predictors (familial CVD, obesity, smoking, diabetes duration, glycemic control, microvascular complications, geographic area, and antihypertensive and lipid-lowering treatment), male sex, older age, and insulin use were significant independent risk predictors (cohort A) and serum triglyceride levels >/=1.69 mmol/l emerged as the only metabolic (negative) prognostic factor (cohort B). In both cohorts, a prior CVD episode, especially myocardial infarction, was by far the strongest predictor of recurrent CVD. CONCLUSIONS: Approximately 6% of unselected diabetic patients in secondary prevention develop recurrent major CVD every year. Those with long-standing previous CVD show a higher incidence of recurrence. Male sex, age, high triglyceride levels, and insulin use are additional predictors of recurrence.

Identifying patients with type 2 diabetes at high risk of microalbuminuria: results of the DEMAND (Developing Education on Microalbuminuria for Awareness of reNal and cardiovascular risk in Diabetes) Study.

BACKGROUND: We evaluated to what extent the presence of risk factors and their interactions increased the likelihood of microalbuminuria (MAU) among individuals with type 2 diabetes. METHODS: Fifty-five Italian diabetes outpatient clinics enrolled a sample of patients with type 2 diabetes, without urinary infections and overt diabetic nephropathy. A morning spot urine sample was collected to centrally determine the urinary albumin/creatinine ratio (ACR). A tree-based regression technique (RECPAM) and multivariate analyses were performed to investigate interaction between correlates of MAU. RESULTS: Of the 1841 patients recruited, 228 (12.4%) were excluded due to the presence of urinary infections and 56 (3.5%) for the presence of macroalbuminuria. Overall, the prevalence of MAU (ACR = 30-299 mg/g) was of 19.1%. The RECPAM algorithm led to the identification of seven classes showing a marked difference in the likelihood of MAU. Non-smoker patients with HbA1c <7% and waist circumference 98 cm and HbA1c >8% showed the highest likelihood of MAU (odds ratio = 13.7; 95% confidence intervals 6.8-27.6). In the other classes identified, the risk of MAU ranged between 3 and 5. Age, systolic blood pressure, HDL cholesterol levels and diabetes treatment represented additional, global correlates of MAU. CONCLUSIONS: The likelihood of MAU is strongly related to the interaction between diabetes severity, smoking habits and several components of the metabolic syndrome. In particular, abdominal obesity, elevated blood pressure levels and low HDL cholesterol levels substantially increase the risk of MAU. It is of primary importance to monitor MAU in high-risk individuals and aggressively intervene on modifiable risk factors.

Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins.

BACKGROUND: Despite the high cardiovascular risk, evidence of efficacy of preventive strategies in individuals with diabetes is scant. In particular, recommendations on the use of aspirin in patients with diabetes mostly reflect an extrapolation from data deriving from other high risk populations. Furthermore, the putative additive effects of aspirin and statins in diabetes remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk, which has also led to the proposal of a polypill. Aim of the study is to evaluate the efficacy of aspirin in the primary prevention of major cardiovascular events in diabetic patients candidate for treatment with statins. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors. METHODS/DESIGN: The ACCEPT-D is an open-label trial assessing whether 100 mg/daily of aspirin prevent cardiovascular events in patients without clinically manifest vascular disease and treated with simvastatin (starting dose 20 mg/die). Eligible patients will be randomly assigned to receive aspirin + simvastatin or simvastatin alone. ELIGIBILITY CRITERIA: male and female individuals aged >=50 years with diagnosis of type 1 or type 2 diabetes, already on treatment with statins or candidate to start the treatment (LDL-cholesterol >=100 mg/dL persisting after 3 months of dietary advise). The primary combined end-point will include cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospital admission for cardiovascular causes (acute coronary syndrome, transient ischemic attack, not planned revascularization procedures, peripheral vascular disease). A total of 515 first events are needed to detect a reduction in the risk of major cardiovascular events of 25% (alpha = 0.05; 1-beta = 0.90). Overall, 5170 patients will be enrolled. The study will be conducted by diabetes specialists and general practitioners. DISCUSSION: The study will provide important information regarding the preventive role of aspirin in diabetes when used on the top of the other strategies aimed to control cardiovascular risk factors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48110081.

Incidence and risk factors for stroke in type 2 diabetic patients: the DAI study.

BACKGROUND AND PURPOSE: Type 2 diabetes mellitus is a strong predictor of cerebrovascular disease, yet few studies have assessed the incidence of stroke and the role of other risk factors in unselected type 2 diabetes mellitus populations. METHODS: We prospectively followed-up 14,432 type 2 diabetes mellitus patients, aged 40 to 97 years, with and without a history of cardiovascular disease at enrollment, and we estimated the incidence of stroke and the hazards ratios with respect to clinical variables. RESULTS: During a 4-year follow-up, 296 incident stroke events were recorded. In persons with no history of cardiovascular disease, the age-standardized incidence of stroke (per 1000 person-years) was 5.5 (95% confidence interval, 4.2 to 6.8) in men and 6.3 (95% confidence interval, 4.5 to 8.2) in women. In persons with a history of cardiovascular disease, it was 13.7 (95% confidence interval, 7.5 to 19.8) in men and 10.8 (95% confidence interval, 7.3 to 14.4) in women. The hazards ratios of stroke incidence varied according to age, sex, and history of cardiovascular disease. Among men with no history, HbA1c and smoking were predictors of stroke. Among patients with a history, the risk factors were, in men, therapy with insulin plus oral agents, treated high total cholesterol and low HDL cholesterol, whereas in women microvascular complications were a risk factor. Previous stroke was a strong predictor of stroke in both sexes. CONCLUSIONS: Age and previous stroke are the main predictors of stroke in diabetes. The combined role of Hba1c, microvascular complications, low HDL cholesterol, and treatment with insulin plus oral agents highlights the importance of diabetic history and clinical background in the development of stroke.

[Recommendations for cardiovascular rehabilitation in diabetes mellitus]. / Raccomandazioni per la riabilitazione cardiovascolare nel paziente con diabete mellito.

Cardiac rehabilitation is accepted as an important component in the management of heart disease. Diabetes Mellitus is a chronic disease frequently associated to ischemic heart disease and both disease require continuing medical care, aggressive treatment of other risk factors, educational programs for self management of disease to prevent acute complication. The scientific community should offer standard of care for management of diabetic patients with coronary artery disease, and should design new strategies to promote prevention in this high risk patients. The need to define characteristics and peculiar problems of diabetics patients with ischemic heart disease encouraged the Board of the Italian Group of Cardiac Rehabilitation and Prevention (GICR) to set up a working group composed of cardiologists and diabetologists chosen on the basis of their proven specific experience. The document is subdivided in six parts. In the first section is described the cardiovascular risks in patients with diabetes and the importance of post-prandial hyperglycemia and glycemic variability. We analyse also the difference in prevalence of ischemic heart disease in Italian diabetic patients compared with other countries. In the second section we described clinical presentation of ischemic heart disease in diabetic patients such as acute myocardial infarction and unstable angina, and the revascularization procedures (balloon angioplasty and coronary bypass surgery). We analysed the differences between the procedures and the evidence-based results. In patients with myocardial infarction we analysed the evidence-based therapy and specific advantages of aspirin, beta-blockers and ace-inhibitor in diabetic patients. In this section we also posed particular attention to the clinical course of patients who underwent bypass grafting and to the impact of diabetes on short and long-term results and on main intervention-related complications including deep infections, mediastinitis, neurological problems, renal failure. In the third section we evaluated the factors responsible of atherosclerosis progression and their treatment, and we underlined that cardiac rehabilitation is less effective for patients with diabetes mellitus. Suggestions proposed in this paper about risk factors are in line with the recommendations of standards guidelines of American Diabetics Association. In patients with concomitant diabetes and ischemic heart disease we suggest blood pressure <130/80, LDL-cholesterol <100 mg/dl, triglycerides <150 mg/dl and daily physical activity. In the fourth section we analysed therapeutic regimens and management of diabetes. We posed particular attention on insulin therapy in acute phase of myocardial infarction and in recent coronary bypass grafting, and chronic use of oral antidiabetic drugs or insulin. In the fifth section we provided some recommendations on the organization of educational programs and physical activity in these patients. In the last section we provided some information on diagnosis of coronary artery disease in diabetes, aim of screening and in which patients is need to perform diagnostic tests. We described the available diagnostic tests with the differences in each method.