1.
Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti-hyperglycaemic drug matters?
Giugliano, D, Ceriello, A, De Nicola, L, Perrone-Filardi, P, Cosentino, F, Esposito, K
Diabetes, obesity & metabolism. 2020;(2):149-157
Abstract
We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease [CVD]) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium glucose co-transporter-2 inhibitors (SGLT-2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT-2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT-2i are effective on the three endpoints, DPP-4i are neutral, while GLP1-RA show mixed results.
2.
Premeal insulin lispro plus bedtime NPH or twice-daily NPH in patients with type 2 diabetes: acute postprandial and chronic effects on glycemic control and cardiovascular risk factors.
Ceriello, A, Del Prato, S, Bue-Valleskey, J, Beattie, S, Gates, J, de la Peña, A, Malone, J
Journal of diabetes and its complications. 2007;(1):20-7
Abstract
OBJECTIVE Two insulin regimens were used to explore acute and chronic postprandial changes in glycemia, lipemia, and metabolic markers associated with increased risk of cardiovascular disease. METHODS An open-label, randomized, two-period crossover study (12 weeks/period) compared a prandial regimen [premeal insulin lispro+bedtime neutral protamine Hagedorn (NPH)] with a basal regimen (twice-daily NPH). There were 30 patients (12 women and 18 men; mean age=61 years) with type 2 diabetes mellitus (mean duration=16 years) who were randomized after a 2-month lead-in with twice-daily NPH treatment. A standard lunch test meal developed according to each patient's caloric needs was administered at the end of each treatment period. RESULTS Insulin lispro was associated with significantly lower postprandial glucose (area under the curve0-5 h=43.54 vs. 57.65 mM/h; P<.001), elevated insulin concentrations, and acutely altered lipid fractions that included an early decrease followed by an increase in free fatty acids, lower triglycerides, elevated total cholesterol, elevated low-density lipoprotein cholesterol (LDL), and elevated high-density lipoprotein cholesterol. After 12 weeks of treatment, insulin lispro+bedtime NPH reduced hemoglobin A1c (HbA1c; mean+/-SE=7.6+/-0.2 vs. 8.2+/-0.2%; P<.001) without increasing hypoglycemia or insulin dose as compared with twice-daily NPH. Furthermore, treatment with the prandial insulin regimen resulted in lower total cholesterol, lower LDL cholesterol, and lower oxidized LDL. CONCLUSION Improved postprandial glycemic control, as observed in a regimen containing both prandial insulin lispro and NPH as the basal insulin, is associated with significantly lower HbA1c and acute modulation of lipid fractions after a test meal. These biochemical modifications may potentially have a favorable impact on cardiovascular risk in patients with type 2 diabetes mellitus.
3.
Controlling oxidative stress as a novel molecular approach to protecting the vascular wall in diabetes.
Ceriello, A
Current opinion in lipidology. 2006;(5):510-8
Abstract
PURPOSE OF REVIEW In diabetes, oxidative stress plays a key role in the pathogenesis of vascular complications; therefore an antioxidant therapy would be of great interest in this disease. RECENT FINDINGS Hyperglycemia directly promotes an endothelial dysfunction--inducing process of overproduction of superoxide at the mitochondrial level. This is the first and key event able to activate all the pathways involved in the development of vascular complications of diabetes. It has recently been shown that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones have a strong intracellular antioxidant activity. SUMMARY Classic antioxidants, such as vitamin E, failed to show beneficial effects on diabetic complications probably because their action is only "symptomatic". The preventive activity against hyperglycemia-induced oxidative stress shown by statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones justifies use of these compounds for preventing complications in patients with diabetes, in whom antioxidant defences have been shown to be defective.