[Show abstract][Hide abstract] ABSTRACT: Diabetes is very common among the elderly. In Italy, more than 20% of people older than 75 suffer from the disease. Many of them are frail, with extensive comorbid conditions, or long-standing diabetes in whom the risk of hypoglycemia is very high. An appropriate multidimensional approach is therefore needed when assessing geriatric syndromes, including frailty, cognitive impairment, poor mobility, reduced vision and hearing, depression, and chronic pain. Although in the last few years the benefits of intensive glucose treatment have been described, it is becoming increasingly clear that over-treatment, particularly in older adults, is a significant problem given the fact that hypoglycemia is related to a number of adverse conditions, including mortality. Consequently, and in the light of a “patient-centered approach”, less stringent A1c goals (such as < 8.0-8.5%) may be appropriate for these patients. The risk of hypoglycemia is highest with insulin and sulphonyl - ureas, mainly glibenclamide. These latter drugs should be avoid in older diabetics. New hypoglycemic agents with a very low risk of hypoglycemia have recently been introduced on the market. This review assesses these drugs and insulin analogs.
Giornale Italiano di Diabetologia e Metabolismo 09/2015; 35(3):239-246.
[Show abstract][Hide abstract] ABSTRACT: Background:
To investigate prospectively the relationship between target values of glycated hemoglobin, blood pressure and LDL-cholesterol, as considered in a combined fashion, and all-cause mortality in patients with type 2 diabetes mellitus.
Two cohorts of patients with type 2 diabetes mellitus, the Gargano Mortality Study (n=810) and the Foggia Mortality Study (n=929), were investigated. A weighted target risk score was built as a weight linear combination of the recommended targets reached by each patient.
In the Gargano Mortality Study and in the Foggia Mortality Study (mean follow up=7.4 and 5.5 years, respectively), 161 (19.9%) and 220 (23.7%) patients died, with an age and sex adjusted annual incidence rate of 2.1 and 2.8 per 100 person-years, respectively. In both study samples the weighted target risk score tended to be linearly associated with all-cause mortality (HR for one point increment=1.30, 95% CI: 1.11-1.53, p=0.001, and HR=1.08, 95% CI: 0.95-1.24, p=0.243, respectively). When the two cohorts were pooled and analyzed together, a clear association between weighted target risk score and all-cause mortality was observed (HR for one point increment=1.17, 95% CI:1.05-1.30, p=0.004). This counterintuitive association was no longer observable in a model including age, sex, body mass index, smoking habit, estimated glomerular filtration rate, albuminuria and anti-diabetic, anti-hypertensive and anti-dyslipidemic treatment as covariates (HR for one point increment=0.99, 95% CI: 0.87-1.12, p=0.852).
In a real life clinical set of patients with type 2 diabetes mellitus, the combination of recommended target values of established cardiovascular risk factors is not associated with all-cause mortality.
PLoS ONE 04/2015; 10(4):e0124536. DOI:10.1371/journal.pone.0124536 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
To develop and validate a parsimonious model for predicting short-term all-cause mortality in patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODS
Two cohorts of patients with T2DM were investigated. The Gargano Mortality Study (GMS, n = 679 patients) was the training set and the Foggia Mortality Study (FMS, n = 936 patients) represented the validation sample. GMS and FMS cohorts were prospectively followed-up for 7.40 ± 2.15 and 4.51 ± 1.69 years, respectively, and all-cause mortality was registered. A new forward variable selection within a multivariate Cox regression was implemented. Starting from the empty model, each step selected the predictor that, once included into the multivariate Cox model, yielded the maximum continuous net reclassification improvement (cNRI). The selection procedure stopped when no further statistically significant cNRI increase was detected.RESULTSNine variables (age, BMI, diastolic blood pressure, LDL cholesterol, triglycerides, HDL cholesterol, urine albumin-to-creatinine ratio, and antihypertensive and insulin therapy) were included in the final predictive model with a C statistic of 0.88 (95% CI 0.82-0.94) in the GMS and 0.82 (0.76-0.87) in the FMS. Finally, we used a recursive partition and amalgamation algorithm to identify patients at intermediate and high mortality risk (hazard ratio 7.0 and 24.4, respectively, as compared with those at low risk). A web-based risk calculator was also developed.CONCLUSIONS
We developed and validated a parsimonious all-cause mortality equation in T2DM, providing also a user-friendly web-based risk calculator. Our model may help prioritize the use of available resources for targeting aggressive preventive and treatment strategies in a subset of very high-risk individuals.
Diabetes care 05/2013; 36(9). DOI:10.2337/dc12-1906 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To assess the impact of relationship between glycated hemoglobin (HbA(1c)), fibrinogen and HDL-cholesterol (HDL-c) on cardiovascular disease in type 2 diabetes.
We investigated i) the relationship of HbA1c, fibrinogen and HDL-c in 375 coronary artery disease (CAD)-negative and 320 CAD-positive diabetic patients and ii) the association between clustering of these three factors and incident major cardiovascular events in 317/320 CAD-positive patients.
i) The relationships between HbA1c and both fibrinogen and HDL-c and between HDL-c and fibrinogen were significant only in CAD-positive patients (β = 10.655, p = 0.002; β = -1.056, p = 0.013; β = -1.751, p = 0.000008, respectively); ii) patients with worse-than-median levels of the three factors showed higher risk for major cardiovascular events than others (HR: 2.22, 95%CI = 1.23-4.02, p = 0.008). Both findings were independent of LDL-c, blood pressure or ongoing therapies.
Our findings suggest interwoven actions of poor glycemic control, low grade inflammation and low HDL-c on atherosclerotic processes in type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals.
A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; n = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; n = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (n = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (n = 169 from Italy, n = 170 from the U.S.).
Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80-2.70) in GHS, 2.31 (95% CI 1.22-4.34) in TVAS, and 1.36 (95% CI 0.88-2.10) in CREED, and 1.56 (95% CI 1.15-2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, P = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (P = 0.035 for interaction).
The ENPP1 K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding.
[Show abstract][Hide abstract] ABSTRACT: The International Diabetes Federation (IDF) indicates age above 45 years as a major risk factor for diabetes and predicts that the number of persons with the disease, which currently stands at 190 million, will double by the year 2025. Several recent trials suggest that tighter glucose control reduces long-term complications in diabetic patients; however, outcomes of tight blood sugar control in the elderly are not known. Nevertheless, the principles of management of type 2 diabetes in the elderly are not different from those in middle-aged patients. There are several reasons to keep glucose control on target, also in the elderly; nonetheless, it should be considered that the risk of hypoglycemia is more deleterious in the elderly and should be avoided. The old and more recent oral glucose-lowering agents, along with the newer types of insulin, will be discussed in this review.