**6. Epidemiology and social relevance of diabetes**

It's well established that diabetes mellitus is a serious health problem in the worldwide population and the most frequent metabolic disease, but, it is hard to know the real incidence in the general population. There are several causes to hold up the adequate epidemiological knowledge: a) the number of studies is limited and difficult to compare among them; b) in many patients diagnosis of DM is not established mostly in older people with very poor symptoms because of the absence of the conventional common disorders: polyuria, polydipsia, polyphagia, weight loss, and asthenia; c) unfortunately, in several cases the diagnosis of diabetes is not reported in the death certificate.

The prevalence in the European countries varies between 2% and 19.5% per 100.000 inhabi‐ tants/year; but the incidence of diabetes increases with age and other factors such as more expectancy life, obesity, increase of glucose intake, and a better and early detection of the disease. Another important feature of the disease is it chronic and progressive character that need treatment for life, acute and chronic complications, and high morbidity and mortality rate. Unfortunately, the current trend towards the increasing incidence worldwide is a reality; with this preface diabetes will be a leading cause of clinical problems for the foreseeable future.

We must not forget that DM includes a group of common metabolic disorders characterized by the presence of hyperglycemia usually followed by glycosuria. There is a number of types of diabetes related to a complex interaction between genetic factors, environmental influence, and lifestyle of patients. The consequences of the metabolic dysregulation secondary to this disorder lead to changes in different organ systems and affect the health and future of many patients. For example, this disease is the leading cause of end-stage renal disease, lower extremity amputations, adult blindness, and chronic heart failure. The therapeutic procedures are aimed at controlling diabetes; in other words, glycemic < 100 mg/dl, negative glycosuria and glycated hemoglobin < 6%.

All patients must be put on an appropriate diet personally designed to help them to reach and maintain normal body weight and to restrict their intake of carbohydrates and fats. They must be encouraged to exercise daily (at least 30 minutes walking), which improves the movement of glucose into muscle cells and blunts the rise in blood glucose that follows carbohydrate ingestion. In all cases, the objective of diabetes treatment is to keep the level of blood sugar within normal values (90-100 mg/dl) as well as to reduce metabolic complications, such as diabetic ketoacidosis, hypoglycemia, hyperosmolar coma, or lactic acidosis, and late compli‐ cations such as circulatory abnormalities, nephropathy, neuropathy, foot ulcers, frequent infections, and retinopathy (retinal changes leading to blindness).

intolerance, nausea, vomiting (metformin, alpha-glucosidase inhibitors) are common patientreported reasons for poor medication adherence. Many studies have demonstrated that adherence to antihyperglycemic agents therapy is related to the number of pills prescribed: several studies have reported that, when patients were prescribed multiple drugs to treat diabetes, adherence significantly decreased, with reductions ranging from 15% to 54%. A prospective study showed a mean adherence of 79% for a triple-daily regimen, 65% for a twicedaily regimen, and 38% for a thrice-daily regimen. Some data from osteoporosis therapies indicate that, compared to a once-daily regimen, a once-weekly treatment can increase medication adherence and compliance. Therefore, a once-weekly oral AHA therapy might

It's well established that diabetes mellitus is a serious health problem in the worldwide population and the most frequent metabolic disease, but, it is hard to know the real incidence in the general population. There are several causes to hold up the adequate epidemiological knowledge: a) the number of studies is limited and difficult to compare among them; b) in many patients diagnosis of DM is not established mostly in older people with very poor symptoms because of the absence of the conventional common disorders: polyuria, polydipsia, polyphagia, weight loss, and asthenia; c) unfortunately, in several cases the diagnosis of

The prevalence in the European countries varies between 2% and 19.5% per 100.000 inhabi‐ tants/year; but the incidence of diabetes increases with age and other factors such as more expectancy life, obesity, increase of glucose intake, and a better and early detection of the disease. Another important feature of the disease is it chronic and progressive character that need treatment for life, acute and chronic complications, and high morbidity and mortality rate. Unfortunately, the current trend towards the increasing incidence worldwide is a reality; with this preface diabetes will be a leading cause of clinical problems for the foreseeable future. We must not forget that DM includes a group of common metabolic disorders characterized by the presence of hyperglycemia usually followed by glycosuria. There is a number of types of diabetes related to a complex interaction between genetic factors, environmental influence, and lifestyle of patients. The consequences of the metabolic dysregulation secondary to this disorder lead to changes in different organ systems and affect the health and future of many patients. For example, this disease is the leading cause of end-stage renal disease, lower extremity amputations, adult blindness, and chronic heart failure. The therapeutic procedures are aimed at controlling diabetes; in other words, glycemic < 100 mg/dl, negative glycosuria

All patients must be put on an appropriate diet personally designed to help them to reach and maintain normal body weight and to restrict their intake of carbohydrates and fats. They must be encouraged to exercise daily (at least 30 minutes walking), which improves the movement of glucose into muscle cells and blunts the rise in blood glucose that follows carbohydrate

improve treatment adherence in many patients with these metabolic disorders.

**6. Epidemiology and social relevance of diabetes**

diabetes is not reported in the death certificate.

132 Treatment of Type 2 Diabetes

and glycated hemoglobin < 6%.

Recent researches into the area of treatment include pancreas transplantation and implantable mechanical insulin infusion system, new medication, as oral hypoglycemic agents, different modalities of insulin, and recent monoclonal antibodies given by intradermal injection way.

From another point of view, it's well known that some clinical trials have demonstrated how angiotensin – converting enzyme (ACE) inhibitors decrease mortality for stroke, myocardial infarction, and other heart problems in patients with cardiovascular disease or high risk diabetes. Nevertheless, up to 20% of patients –mostly women-are unable to tolerate captopril, enalapril, ramipril or others ACE drugs mainly due to persistent and improductive cough, or even other side effects such as hypotension, renal dysfunction or angioneurotic edema, according to our personal experience [14, 15]. *The Action in Diabetes and Vascular Disease: preterAx and DiamicroN Controlled Evaluation* (ADVANCE) Trial, using perindopril combined with gliclazide was designed to assess outcome of macrovascular and microvascular disease on diabetic patients [15]. Ramipril did not affect heart failure events in low-risk patients according to the findings reported in the DREAM Study [16]. It's possible to believe that when the absolute risk of heart failure is low, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are not able to reduce the incidence of heart failure. Myocardial infarction rate was lower in TRASCEND study compared to HOPE trial. It is possibly due to that patients included in the TRASCEND study were at lower risk compared with those admitted in HOPE (Heart Outcomes Prevention Evaluation) Study Ongoing Trial [17]; the population of women was about 40% in the TRASCEND study while only 2% was reported in ONTARGET trial, and other previous studies of ACE inhibitors.

It is also important to realize, according to numerous clinical experiences and data from TRASCEND study, that telmisartan (angiotensin-receptor blockers) could be regarded as a potential treatment for patients with vascular disease or high-risk diabetes when the patients are unable to tolerate antihypertensive drugs as ACE inhibitors.

Concerning hypertension and based on data from many large-scale clinical trials, international guidelines recommend two drugs with subsequent complementary mechanisms of action to control BP in most patients, with initial combination therapy when Systolic Blood Pressure (SBP) is 150 mmHg or Diastolic Blood Pressure (DBP) is > 100 mmHg above target [18, 19]. These guidelines also favour the use of a fixed dose combination for the clinical practice [20].

From the clinical point of view, it is significant to understand the strong pathophysiological relationship between diabetes and hypertension. The latter is predicted to rise dramatically with a number of cases expected to reach 1560 million worldwide by 2025 [21]. Unfortunately, this is coupled with low rates of BP control (target <130/80 mmHg), despite the increased use of antihypertensive treatment. It must be emphasized an early and sustained BP control in order to reduce the long-term burden associated with this condition. To address challenges for now and the future, some international guidelines recommend early treatment with agents that have complementary mechanism of action. These combinations have benefits related to compliance, efficacy and safety for the patients.

The difficulty in getting good metabolic and clinical control of BP in many patients, may result in the development of acute clinical disorders or chronic complications. Physicians must keep in mind when the patient develops acute confusional states or coma; these events could be due to DM *per se*, or other pathologies developed in those patients, such as hepatic failure, renal disease, stroke, respiratory distress, poisoning or drug overdose; the distinction between coma secondary to inadequate level of insulin, and non diabetic disease is crucial for the prognosis of the patients.
