Diabetes in the third millennium: prognosis improves, but juvenile forms are more frequent.

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by an imbalance between insulin secretion and response to the hormone, which translate in high blood glucose levels. This condition represents one of the main cardiovascular risk factors, along and often in association with arterial hypertension and an abnormal lipid profile, thus multiplying the probability of cardiovascular complications.

Treatment of T2DM includes modification of lifestyle and pharmacological therapy, which is constantly enriched with new weapons effective in controlling this pathology. Recently, new therapies have emerged which radically changed the management of diabetes, by improving not only glycaemic control, but also cardiovascular mortality and quality of life (Table ). In the EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose) trial, Empagliflozin (10 mg or 25 mg) decreased all-cause mortality mainly as a consequence of the significant reduction of the risk of death for cardiovascular causes and hospitalization for heart failure. The Kaplan–Meier curve after 3.1 years of median follow-up have shown a net life gain of 12 months. The CANVAS (Canagliflozin Cardiovascular Assessment Study) showed superiority of Canagliflozin over placebo in reducing the composite endpoint of cardiovascular mortality, stroke, and non-fatal myocardial infarction. These data support a kind of class effect in the global improvement of the prognosis in diabetic patients but with specific differences. Further evidence is derived from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) study. In the group treated with Liraglutide, there was a lower number of cardiovascular events, reduction of all-cause mortality, and cardiovascular mortality. There was also a better safety profile, as far as hospitalization for heart failure, at variance from other drugs of the same class. The pattern of cardiovascular benefit was different from the SGLT-2 (sodium-glucose transport protein 2) shown in the EMPA-REG study: timewise the latter demonstrate early effect, as to suggest a hemodynamic effect of the drug as compared to the GLP-1 (glucagon-like peptide-1) receptor agonist which manifest its effect later, suggesting an action on the progression of atherosclerosis.

These important therapeutic achievements are counterbalanced by the almost epidemic progression of the disease, partly attributable to the aging population, and partly to the increased diagnosis in the younger age groups. It is apparent that the diagnosis of T2DM is increasing among youth worldwide. Among the various factors capable of influencing the development of this pathology, lifestyle has a primary role, considering that obesity, as a result of excessive eating and lack of physical activity, represents the main risk factor in almost 80% of the cases, and overweight alone contributes to 10% of the cases. There is limited knowledge on the macrovascular complications in children and adolescents with T2DM: atherosclerosis requires many years to develop, and could be inferred that age itself, in some way, could protect the young patients.

Among the factor associated with disorders of glucose metabolism and diabetes, fructose consumption, from beverages and sweetened juices, has an important role. The excessive consumption of fructose triggers a rapid and persistent increased blood level of uric acid, which, in turn, increases oxidative stress, leading to diabetes, metabolic syndrome, and hypertension in the young population. It is then crucial to develop prevention programmes aimed at early reduction of the main risk factors with interventions addressing modification of lifestyle, behaviour, and nutritional habits of children and adolescents.

Conflict of interest: none declared.

Table 1

Main outcomes with statistical significance

Clinical trial	Outcomes	Hazard ratio	95% confidence interval
EMPA-REG	All-causes mortality	0.68	0.57–0.82
	Cardiovascular deaths	0.62	0.49–0.77
	Hospitalization for heart failure	0.65	0.50–0.85
CANVAS	3-points MACE	0.86	0.75–0.97
	Hospitalization for heart failure	0.67	0.52–0.87
LEADER	All-causes mortality	0.85	0.74–0.97
	3-points MACE	0.87	0.78–0.97
	Cardiovascular deaths	0.78	0.66–0.93

3-points MACE, cardiovascular deaths, non-fatal myocardial infarction, and non-fatal stroke.