Hyperglycemia, hypoglycemia and glycemic variability in the elderly: a fatal triad?

Diabetes mellitus is one of the most important causes of cardiovascular morbidity and mortality; the incidence of chronic complications of diabetes appears to be closely related to the degree of hyperglycaemia. However, results of clinical trials showed that intensive treatment of hyperglycaemia prevents microvascular complications, but has little or no effect on the incidence of cardiovascular events. Different hypoglycaemic drugs show different effects on cardiovascular risk. However, those trials have shown a neutral effect on cardiovascular mortality. This paradoxical result could be explained with the frequent use, in the past, of glucose-lowering agents capable of increasing the risk of hypoglicemia, glycemic variability and weight gain. In conclusion, an adequate glycemic control, in particular in elderly patients, should be achieved, whenever possible, using agents not inducing hypogycemia, glucose fluctuations, and weight gain. In fact, hypoglycaemia and glucose variability should be considered as independent cardiovascular risk factors to a similar extent to hyperglycemia. In this article, the author will review literature supporting the hypothesis that hyperglycemia, hypoglycaemia and glycemic variability are a fatal triad capable of increasing morbidity and mortality in patients with diabetes mellitus.  Riassunto Il diabete mellito è una delle più importanti cause di morbilità e mortalità cardiovascolare, ed è stata dimostrata una stretta correlazione tra compenso glicometabolico ed incidenza di complicanze croniche del diabete mellito. Tuttavia, negli studi di intervento, il controllo accurato dell’iperglicemia sembra poter prevenire le complicanze microvascolari, ma ha effetti soltanto marginali sull’incidenza di eventi cardiovascolari secondari a malattia macrovascolare. Inoltre, i grandi trial di intervento hanno mostrato come la riduzione degli eventi cardiovascolari non si accompagni ad una riduzione della mortalità cardiovascolare. Tale paradosso potrebbe essere spiegato dal fatto che spesso, in passato, per ottenere un miglioramento glicometabolico si sono utilizzati farmaci ipoglicemizzanti in grado di aumentare il rischio ipoglicemico, la variabilità glicemica ed il peso corporeo. In conclusione, il miglioramento del compenso glicemico, specie nel paziente anziano, dovrebbe essere ottenuto, quando possibile, con farmaci a basso rischio ipoglicemico e non inducenti aumenti di peso, per evitare gli effetti negativi di ipoglicemie e eccessive fluttuazioni della glicemia che di per sé costituiscono dei fattori di rischio cardiovascolari al pari dell’iperglicemia. In questo articolo, si esplorerà l’ipotesi che iperglicemia, ipoglicemia e variabilità glicemica costituiscano una triade fatale in grado di aumentare morbilità e mortalità nei pazienti affetti da diabete mellito

Effects of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight: A Meta-Analysis

Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for “exenatide,” “liraglutide,” “albiglutide,” “semaglutide,” and “lixisenatide” was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of −1.0 [−1.3; −0.6] kg/m2. Considering the average BMI at baseline (32.4 kg/m2) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction

Effects of a Short Educational Program for the Prevention of Foot Ulcers in High-Risk Patients: A Randomized Controlled Trial

Background. Patient education is capable of reducing the risk for diabetic foot ulcers. However, specific education on foot ulcer prevention was either included in broader programs addressing different parts of diabetes care or provided with time- and resource-consuming curricula. The aim of the study is to assess the feasibility and efficacy of a brief educational program for the prevention of diabetic foot ulcers in high-risk patients. Methods. The study was performed on type 2 diabetic patients, randomized in a 1 : 1 ratio either to intervention or to control group. The principal endpoint was the incidence of foot ulcers. The intervention was a two-hour program provided to groups of 5–7 patients, including a 30-minute face-to-face lesson on risk factors for foot ulcers, and a 90-minute interactive session with practical exercises on behaviors for reducing risk. Results. The study was prematurely terminated due to a highly significant difference in outcome between the two treatment groups. The final sample was therefore composed of 121 patients. Six patients, all in the control group, developed ulcers during the 6-month follow-up (10% versus 0%, p=0.012). Conclusions. A brief, 2-hour, focused educational program is effective in preventing diabetic foot ulcers in high-risk patients

Direct‐acting antivirals for HCV treatment in older patients: A systematic review and meta‐analysis

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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