Psychopathology and continuous subcutaneous insulin infusion in type 1 diabetes.

AIM: Continuous subcutaneous insulin infusion (CSII) is used as an option in patients with diabetes failing to multiple daily injections (MDI). Psychological factors may play a relevant role in the failure to attain therapeutic goals in patients on MDI. This could lead to an overrepresentation of psychopathology in patients treated with CSII. METHODS: A consecutive series of 100 patients with type 1 diabetes was studied, collecting main clinical parameters and assessing psychopathology with the self-reported questionnaire Symptom Checklist 90-revised. Patients on CSII were then compared with those on MDI. RESULTS: Of the 100 enrolled patients, 44 and 56 were on CSII and MDI, respectively. Among men, those on CSII were younger than those on MDI; conversely, no difference in age was observed in women. Women on CSII showed higher scores on most Symptom Checklist 90 subscales than those on MDI, whereas no differences were observed in men. CONCLUSION: Women with type 1 diabetes treated with CSII display higher levels of psychopathology than those on MDI. This is probably the consequence of the fact that patients selected for CSII are those failing to MDI. Higher levels of psychopathology could represent a limit for the attainment and maintenance of therapeutic goals with CSII.

Targeting educational therapy for type 2 diabetes: identification of predictors of therapeutic success.

Patient education is a key component of diabetes care. Limits in resources often prevent the participation of many patients with type 2 diabetes to structured education programs. The identification of predictors of response to group education could help in selecting those patients in whom the intervention is more cost-effective. A structured interactive group program was proposed to a consecutive series of 150 type 2 diabetes patients, who were then followed prospectively in 24 months, with measurements of HbA1c, BMI, quality of life, eating habits. For comparison, another consecutive series of 113 patients who had received no intervention was also observed for 12 months. A significant reduction in HbA1c was observed in the intervention group at 12 and 24 months (from 7.5 ± 1.4 to 6.9 ± 1.2 and 6.6 ± 1.1% at 12 and 24 months, respectively, both P < 0.01), with no variation in BMI and quality of life. A sustained reduction in total energy, protein, and fat intake was observed after education. The proportion of success (HbA1c < 7% and/or HbA1c reduction from baseline > 1%) in the intervention group was 60.7% (vs. 38.1% in controls) and 63.3% at 12 and 24 months, respectively. In the intervention group, patients with success at 12 months showed lower baseline HbA1c, BMI, duration of diabetes, protein, and cholesterol intake. Patients with a lower duration of diabetes appear to have a greater response to structured group education, whereas age is not a predictor of response. Therefore, educational intervention should be planned in the earlier phases of the disease.

DPP-4 inhibitors and lipids: systematic review and meta-analysis.

INTRODUCTION: Lipid profile is an important determinant of cardiovascular risk in type 2 diabetic patients. Available glucose-lowering agents can affect lipid levels. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to reduce total cholesterol, but results are inconsistent across trials. The present metaanalysis was designed to assess the effect of DPP-4 inhibitors on blood lipids, verifying possible differences across compounds of this class. METHODS: An extensive search of Medline and the Cochrane Library (any date up to December 31, 2010, restricted to randomized clinical trials, published in English) was performed for all trials containing, in any field, the words "sitagliptin," "vildagliptin," "saxagliptin," "alogliptin," "linagliptin," and/or "dutogliptin." Completed but unpublished trials were identified through a search of the ClinicalTrials.gov website, using the same keywords as above. Differences in the endpoint levels and absolute or percent variations of lipids were assessed. A metaregression was performed on the trials specified above to assess the effect of putative moderators on the effect of DPP-4 inhibitors on plasma lipids, considering all drugs together and each one separately. RESULTS: Although the number of trials of appropriate size and duration was high (n=53), only a small fraction of those (n=17) reported data on endpoint total, high-density lipoprotein, and low-density lipoprotein cholesterol, and triglyceride. The difference-in-means for endpoint versus baseline total cholesterol in patients on DPP-4 inhibitors treatment was significantly higher in comparison with controls, meaning that treatment with DPP-4 inhibitors is associated with a significant reduction in total cholesterol (-0.18 [-0.29; -0.06] mmol/L (-7.0 [-11.2; -2.50] mg/dL); P=0.002). CONCLUSIONS: This meta-analysis suggests a possible beneficial effect of DPP-4 inhibitors on cholesterol, which, although small, could contribute to the reduction of cardiovascular risk.

Post-prandial glucose and diabetic complications: systematic review of observational studies.

Post-prandial hyperglycemia is considered a relevant therapeutic target in type 2 diabetic patients, and it could represent per se an independent risk factor for diabetic complications. Aim of the present systematic review is to collect and summarize evidence from observational studies on the relationship between post-prandial glucose (PPG) and cardiovascular or microvascular disease in patients with diabetes. An extensive search of Medline (any date up to December 31, 2010) was performed for all longitudinal epidemiological studies with a cohort design. The following endpoints were taken into consideration: death from any cause; cardiovascular death and micro- and macrovascular complications. The number of epidemiological studies assessing the relationship between PPG and microvascular or cardiovascular disease in subjects with diabetes is surprisingly scarce. In fact, of the 391 retrieved studies, only 8 fulfilled the inclusion criteria. Most of those investigations enrolled small samples, which in many instances were not representative of the general population. Furthermore, the assessment of PPG varied widely across studies. These considerations prevent any formal meta-analysis. Despite this, the few available studies show that higher PPG is associated with increased all-cause and cardiovascular death, incidence of major cardiovascular events (including myocardial infarction and stroke), and progression of diabetic retinopathy.

Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials.

OBJECTIVE: Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists. DESIGN AND METHODS: MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events. RESULTS: Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50-1.08), P = .12 (0.85 (0.50-1.45), P = .55, and 0.69 (0.40-1.22), P = .20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25-0.83), P = .009, and 1.05 (0.63-1.76), P = .84, respectively. CONCLUSIONS: To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.

Predictors of response to dipeptidyl peptidase-4 inhibitors: evidence from randomized clinical trials.

AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in the treatment of type 2 diabetes. Available sub-group analysis of clinical trials does not allow a clear identification of predictors of therapeutic response to these drugs. The aim of this study is the assessment of predictors of response to DPP-4 inhibitors. MATERIALS AND METHODS: A meta-analysis was performed, exploring correlation between 24-week effects on HbA(1c) of maximal doses of DPP-4 inhibitors, compared either with placebo or with other active drugs, matches to baseline characteristics of patients enrolled in 63 randomized clinical trials, either published or unpublished but disclosed on different websites were studied. RESULTS: DPP-4 inhibitors significantly reduce HbA(1c) at 24 weeks [by 0.6 (0.5-0.7)%] when compared with placebo; no difference in HbA(1c) was observed in comparisons with thiazolidinediones and α-glucosidase inhibitors, whereas sulfonylureas and metformin produced a greater reduction of HbA(1c) , at least in the short term. DPP-4 inhibitors produced a smaller weight gain than thiazolidinediones, and showed a lower hypoglycaemia risk than sulfonylureas. The placebo-subtracted effect of DPP-4 inhibitors on HbA(1c) was greater in older patients and in those with lower fasting plasma glucose at baseline. Similar results were obtained in comparisons with thiazolidinediones and metformin. CONCLUSIONS: Although drugs for type 2 diabetes are studied in heterogeneous samples of patients, their efficacy can be predicted by some clinical parameters. DPP-4 inhibitors appear to be more effective in older patients with mild/moderate fasting hyperglycaemia. These data could be useful for a better definition of the profile of patients who are likely to benefit most from these drugs.

Doses of insulin and its analogues and cancer occurrence in insulin-treated type 2 diabetic patients.

OBJECTIVE: Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of different insulin analogues with cancer incidence. RESEARCH DESIGN AND METHODS: A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5-24.9, 25-29.9, and >or=30 kg/m(2)) were considered as additional categorical matching variables. RESULTS: During a median follow-up of 75.9 months (interquartile range 27.4-133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day [0.10-0.39] versus 0.16 IU/kg/day [0.12-0.24], P = 0.036). Incident cancer was associated with a dose of glargine >or=0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 [95% CI 2.18-13.53], P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues. CONCLUSIONS: The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 1 diabetes: a meta-analysis.

Continuous subcutaneous insulin infusion (CSII) is considered an option for type 1 diabetic patients unsatisfactorily controlled with multiple daily injections (MDI). Short-acting analogs are superior to regular human insulin in CSII. This meta-analysis is aimed at assessing the advantages of short-acting analog-based CSII over MDI in type 1 diabetes. Randomized clinical trials (RCTs) comparing CSII (with analogs) and MDI for at least 12 weeks in type 1 diabetic patients were retrieved, assessing between-group differences in HbA1c and incidence of hypoglycemia. A total of 11 RCTs was included in the analysis. CSII was associated with a significant improvement of HbA1c in comparison with MDI (standardized difference in mean: -0.3 [-0.4;-0.1]%; P < 0.001). No significant difference was observed in the rate of severe hypoglycemic episodes. The reduction of HbA1c with CSII was evident in trials enrolling patients with mean age greater than 10 years, but not in younger children. Available data justify the use of CSII for basal-bolus insulin therapy in type 1 diabetic patients unsatisfactorily controlled with MDI.

Cardiac safety profile of rosiglitazone: a comprehensive meta-analysis of randomized clinical trials.

BACKGROUND: Some meta-analyses of randomized clinical trials suggested that rosiglitazone could be associated with increased risk for myocardial infarction (MI). Available meta-analyses, based on studies sponsored by GlaxoSmithKline (GSK), failed to include all trials performed with rosiglitazone. Aim of this analysis is the assessment of the cardiovascular risk with rosiglitazone, using a comprehensive data set. METHODS: Results of 164 trials with duration >4 weeks were retrieved from http://ctr.gsk.co.uk/welcome.asp and from Medline, while unpublished studies were identified from www.clinicaltrials.gov. A total of 164 trials (42,922 and 45,483 patient years for rosiglitazone and comparators, respectively) were included in the analysis. RESULTS: The OR for all-cause and cardiovascular mortality with rosiglitazone was 0.93[0.76;1.14] and 0.94[0.68;1.29], respectively; rosiglitazone-associated risk for nonfatal MI and heart failure was 1.14[0.90;1.45] and 1.69[1.21;2.36], respectively. The risk of heart failure was higher (2.20[1.28;3.78]) when rosiglitazone was administered as add-on therapy to insulin. CONCLUSIONS: Figures for rosiglitazone-associated risk for myocardial infarction could be lower than those previously reported on the basis of a smaller number of clinical trials. No increase of all-cause or cardiovascular mortality were observed with rosiglitazone. Conversely, treatment with rosiglitazone is associated with a relevant increase in the risk of heart failure, particularly in insulin-treated patients.

Failure to metformin and insulin secretagogue monotherapy: an observational cohort study.

The aim of the present cohort study is the assessment of treatment failure rates in patients on monotherapy with metformin or insulin secretagogues, observed in a routine clinical setting. A cohort of patients without any pharmacological treatment was also observed. A retrospective observational cohort study was performed on a consecutive series of 2,020 type 2 diabetic patients receiving monotherapy with an oral agent (metformin or insulin secretagogue, n = 1,126) or drug-naive (n = 894). HbA1c and prescribed hypoglycemic therapy were recorded yearly. Patients were followed until death, change of residence, failure to treatment, or up to 48 months. The mean duration of follow up was 34.8 ± 18.0 months. In a Cox regression analysis, metformin was associated with a significant reduction, and insulin secretagogues with a significant increase, in the risk of failure to therapy during follow up. When duration of diabetes and baseline BMI were added to the model, insulin secretagogues, but not metformin, were still associated with increased risk of failure. In conclusion, insulin secretagogues are associated with increased failure rate in comparison with metformin. This difference could be due to detrimental effect of secretagogues, rather than to a beneficial action of metformin.

Sulphonylureas and cancer: a case-control study.

This study was aimed at the assessment of incidence of malignancies in type 2 diabetic patients treated with different sulphonylureas. A matched case-control study was performed. Cases were 195 diabetic patients aged 69.0 +/- 9.2 years who had an incident malignancy. Controls were 195 diabetic patients, unaffected by cancer, who were matched with the corresponding case for age, sex, duration of diabetes, BMI, HbA1(c), comorbidity, smoking and alcohol abuse. Exposure to hypoglycaemic drugs during the 10 years preceding the event (or matching index date) was assessed. After adjusting for concomitant therapies, exposure to metformin and gliclazide for more than 36 months was associated with a significant reduction in the risk of cancer (adj. ORs with 95% CI: 0.28 (0.13-0.57), p < 0.001, and 0.40 (0.21-0.57), p = 0.004, respectively). Conversely, use of glibenclamide for at least 36 months was associated with increased incidence of malignancies (adj. OR 2.62 (1.26-5.42); p = 0.009). Treatment with insulin, thiazolidinediones, or acarbose, was not associated with significant differences in the incidence of cancer. Long-term treatments with individual sulphonylureas could have differential effects on the risk of cancer. In particular, the possible protective effect of gliclazide, as well as the risk associated with glibenclamide, deserves further investigation.

Metabolic syndrome and cardiovascular mortality in older type 2 diabetic patients: a longitudinal study.

BACKGROUND: Although age does not seem to modify the association of the metabolic syndrome (MS) with cardiovascular risk in middle-aged individuals, no comparison of risks associated with MS between old and middle-aged persons has been reported so far. METHODS: An observational study was performed on a consecutive series of 1716 type 2 diabetic outpatients (age range: 28-96 years). The diagnosis of MS was made following either the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) or the International Diabetes Federation (IDF) criteria. RESULTS: The difference in cardiovascular mortality between patients with and without MS was significant up to the age of 70 years. After adjusting for age and sex, hazard ratios of MS for cardiovascular mortality were 3.03 (95% confidence interval, 1.45-6.29), 1.56 (0.91-2.68), and 1.17 (0.42-3.22) in patients < or =70, 71-80, and >80 years old, respectively. CONCLUSIONS: MS is associated with increased cardiovascular risk in middle-aged type 2 diabetic patients, and the clinical utility of this category in older diabetic individuals is questionable.

Rosiglitazone and risk of cancer: a meta-analysis of randomized clinical trials.

OBJECTIVE: Despite experimental data suggesting a protective effect of peroxisome proliferator-activated receptor-gamma agonists with respect to malignancies, results of available epidemiological studies on the incidence of cancer in rosiglitazone-treated patients are not univocal. The aim of this meta-analysis of randomized clinical trials is to assess the effect of rosiglitazone on the incidence of cancer. RESEARCH DESIGN AND METHODS: Randomized clinical trials of rosiglitazone with duration of >24 weeks were retrieved through Medline and from the GlaxoSmithKline Web site, which reports main results of all trials sponsored by GlaxoSmithKline; incident malignancies were retrieved from the summary of serious adverse events. Proportions of outcome measures across treatment groups were compared by odds ratios (ORs) and 95% CI. Considering differences in the duration of follow-up among treatment arms in some of the trials, we also calculated the incidence of cancer in rosiglitazone and control groups. RESULTS: Eighty trials, enrolling 16,332 and 12,522 patients in the rosiglitazone and comparator groups, respectively, were retrieved. Rosiglitazone was not associated with a significant modification of the risk of cancer (OR 0.91 [95% CI 0.71-1.16], P = 0.44). The incidence of malignancies was significantly lower in rosiglitazone-treated patients than in control groups (0.23 [0.19-0.26] vs. 0.44 [0.34-0.58] cases/100 patient-years; P < 0.05). CONCLUSIONS: The use of rosiglitazone appears to be safe in terms of incidence of cancer, whereas its possible protective effect needs to be further investigated.

Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study.

The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.

Comparison of different drugs as add-on treatments to metformin in type 2 diabetes: a meta-analysis.

BACKGROUND: Metformin is recommended as first-line treatment in type 2 diabetic patients. Several agents can be used as add-on treatments in metformin monotherapy failure. Most available clinical trials on the hypoglycemic efficacy of different drugs were performed either in monotherapy or in combination with agents other than metformin. Aim of the present meta-analysis is to collect available information on the efficacy of different hypoglycemic drugs, in combination with metformin, in patients failing to metformin, or to other oral monotherapies. METHODS: An extensive Medline search, together with manual search of references from retrieved articles, was performed to identify randomized clinical trials comparing the efficacy on HbA1c of different agents, compared with placebo or with other active drugs, in combination with metformin, in patients failing to oral hypoglycemic therapy. HbA1c reduction at 16-36 months was considered for meta-analysis. RESULTS: A total of 27 clinical trials were retrieved. Combining the results of different placebo-controlled trials, sulphonylureas, alpha-glucosidase inhibitors and thiazolidinediones induced a reduction [95%CI] of HbA1c of 0.85 [0.78; 0.94], 0.61 [0.55; 0.67], 0.42 [0.40; 0.44]%, respectively. In direct comparisons, sulphonylureas induced a greater reduction of HbA1c (of 0.17 [0.16; 0.18]%) than thiazolidinediones, and had a similar effect as insulin. CONCLUSIONS: When combined with metformin, sulphonylureas and alpha-glucosidase inhibitors show a similar efficacy on HbA1c. The effects of drugs used as add-on to metformin monotherapy could be different from those observed in monotherapy.

Skin autofluorescence in type 2 diabetes: beyond blood glucose.

BACKGROUND AND AIM: Skin autofluorescence (AF), which has been proposed as a measure of tissue content of advanced glycation end-products, is a predictor of health outcomes in diabetic patients. Aim of this study is the assessment of parameters associated with increased AF in a sample of type 2 diabetic patients. METHODS: AF was determined in a consecutive series of type 2 diabetic 92 patients aged 69.1+/-12.4 years. Univariate and multivariate correlations with several clinical and chemical parameters were assessed. RESULTS: A significant (p<0.01) correlation of AF was found with age (r=0.33) and HbA1c (r=0.34). After adjusting for age and HbA1c, micro- or macrovascular complications of diabetes were associated with higher AF. Furthermore, a higher AF was found in patients with metabolic syndrome (2.7+/-1.0 AU versus 2.2+/-0.7 AU; p<0.05). Waist circumference, triglyceride, and HDL cholesterol showed a significant correlation with AF after adjustment for age and HbA1c (adj. r=0.30, 0.29, and -0.27; all p<0.05). CONCLUSIONS: Skin autofluorescence in type 2 diabetic patients is associated not only with degree of hyperglycaemia and age, but also with adiposity and metabolic syndrome.

Prognostic value of serum liver enzymes levels in type 2 diabetic patients.

BACKGROUND: Elevated liver enzymes are associated with cardiovascular disease, while their relationship with cancer-related mortality has not been assessed so far in diabetic patients. METHODS: An observational cohort study was performed on a consecutive series of 1952 type 2 diabetic patients. The association of liver enzymes with all-cause and cause-specific mortality was assessed. Information on all-cause mortality was obtained by the City of Florence Registry Office. RESULTS: The average duration of follow-up was 6.4 +/- 2.7 years. Over that period, 362 deaths were recorded (26.9%), with a yearly mortality rate of 4.2%. Age- and sex-adjusted HR of all-cause mortality for gamma glutamyl-transpeptidase (gamma-GT) gamma-GT > 40 U/l was 1.610 [1.245-2.082]. An increased cardiovascular mortality rate was observed in patients with elevation of gamma-GT, and gamma-GT and/or alanine aminotransferase (ALT), when compared with the rest of the sample (15.3 vs 10.8%, p < 0.05; and 15.2 vs 10.7%, p < 0.05, respectively). Similar results were observed when considering cancer-related mortality. The association of higher gamma-GT levels with all-cause, cardiovascular, and cancer-related mortality was confirmed at a multivariate analysis after adjustment for potential confounders. CONCLUSIONS: The present study shows that, in type 2 diabetic patients, higher gamma-GT, but not ALT, is associated with increased mortality for cardiovascular disease and malignancies.

Are comorbidity indices useful in predicting all-cause mortality in Type 2 diabetic patients? Comparison between Charlson index and disease count.

BACKGROUND AND AIMS: Several studies have shown that comorbidity is important in predicting morbidity and mortality in the general population. However, few studies have assessed the validity of comorbidity indices in diabetic patients. The aim of the present study was to compare the predictive value of disease count and Charlson's Comorbidity Index (CCI) for 3-year mortality in type 2 diabetic (T2D) patients. METHODS: The study was performed on a consecutive series of 1667 T2D outpatients. Comorbidity was assessed using Charlson's index, whereas the diseases used to calculate Charlson's score were taken into account for disease count. Information on all-cause mortality over the 3-year follow-up period was obtained from the City of Florence Registry Office. RESULTS: Mean duration of follow-up (+/-SD) was 31.4+/-10.6 months. One hundred and ninety-nine (11.9%) patients died during follow-up, with a yearly mortality rate of 4.7%. At multivariate analysis, after adjustment for sex and age, each additional disease was associated with a 54 [37-77]% increase in all-cause mortality. Mortality increased by 31 [21-41]% for each incremental point of Charlson's comorbidity score. CONCLUSIONS: A simple disease count is as predictive of mortality in T2D patients as the more complex Charlson's index. The possible usefulness of specific comorbidity indices in predicting incident disability in diabetic subjects needs to be further investigated.

Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin.

BACKGROUND: Several studies have shown an increase of mortality in diabetic patients treated with combinations of sulphonylureas and biguanides. Comparisons between different insulin secretagogues in combination with metformin with respect to all-cause mortality have not been reported so far. METHODS: An observational cohort study was performed on a consecutive series of 2002 outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were receiving combinations of insulin secretagogues and biguanides at enrollment. Three-year mortality was assessed through research in the City of Florence Registry Office. RESULTS: During follow-up, 295 deaths were recorded. Among patients on combined secretagogue and biguanide treatment, glibenclamide was associated with a significantly higher yearly mortality (8.7%) than repaglinide (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p < 0.0001). After adjusting for potential confounders (including age; duration of diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment; metformin doses; Charlson co-morbidity score; CCS), mortality remained significantly higher in patients treated with combinations of glibenclamide and metformin when compared to those treated with different insulin secretagogues (OR with 95% CI: 2.09 [1.07;4.11]). CONCLUSIONS: In the present study, sulphonylureas with greater selectivity for beta-cell receptors, such as glimepiride and gliclazide, were associated with a lower mortality when used in combination with metformin in comparison with glibenclamide. Safety of such combinations deserves further investigation.