**2. Prevention of CVDs and control of blood pressure (BP)**

Seven modifiable well-known risk factors of atherosclerotic CVDs are high BP, glucose intolerance, physical inactivity, tobacco use, dyslipidemia, unhealthy diet and overweight/obesity (**Figure 1**).

#### **2.1. High blood pressure (BP)**

Hypertension is the most prevalent risk factor for development of cardiovascular and kidney disease. In 2008, worldwide, approximately 40% of adults aged 25 had been diagnosed with hypertension and its prevalence is predicted to increase by almost 60% in the next 2 decades [11, 12]. Hypertension is responsible for at least 45% of deaths due to heart disease and 51% of deaths due to stroke [11, 12]. High BP is the leading risk factor in the world especially in the non-industrialized countries [13]. In fact there is some increase in cardiovascular risk in patients with BP 120–140/80–90 (i.e. pre-hypertension) than in those with BP less than 120/80 (i.e. normal BP) even in the general population [14]. Untreated BP <120/<80 mmHg (i.e. normal

**Figure 1.** The seven modifiable risk factors of atherosclerotic cardiovascular disease.

3.7 million deaths due to diabetes and its complications occur before the age of 70 years [2]. Up to 80% of deaths in type 2 diabetes are cardiovascular diseases (CVDs) related. Persons with impaired glucose tolerance are also almost three times more likely to develop coronary heart disease and other major cardiovascular events than people with normal glucose tolerance. In fact, CVDs alone account for nearly 30% of all deaths worldwide and 27% in lowincome and middle-income countries [3, 4]. Thus, in one hand, there is a need to prevent and treat diabetes, and on the other hand, considering various possible risk factors, the impaired glucose tolerance itself and CVDs have to be prevented both at individual and population

This chapter will focus on the principles of management of type 2 diabetes at individual and population levels to consider while following the guidelines and managing diabetes and its epidemic. Management is defined as the act or skill of dealing with people or situations in a successful way [5]. The term management in the chapter covers clinical management, research and public health perspectives. Public health is the practice of preventing disease and promoting good health within groups of people, from small communities to entire countries [6]. Primary prevention requires a focus on individuals known to be at risk for disease, i.e. the high-risk strategy with interventions focused on high-risk group, for example on people with glucose intolerance. A large proportion of the reductions in coronary heart disease mortality experienced in many high-income nations since the 1960s have been ascribed to the interventions in people at elevated risk [7]. However, individuals with markedly elevated levels of risk factors are relatively uncommon in the population. The majority of CVD events occur in individuals with average or only mildly adverse levels of risk factors [7, 8]. Therefore, population-wide strategies are also essential. Health promotion and disease prevention strategies must embrace both high-risk and population

**2. Prevention of CVDs and control of blood pressure (BP)**

Seven modifiable well-known risk factors of atherosclerotic CVDs are high BP, glucose intolerance, physical inactivity, tobacco use, dyslipidemia, unhealthy diet and overweight/obesity

Hypertension is the most prevalent risk factor for development of cardiovascular and kidney disease. In 2008, worldwide, approximately 40% of adults aged 25 had been diagnosed with hypertension and its prevalence is predicted to increase by almost 60% in the next 2 decades [11, 12]. Hypertension is responsible for at least 45% of deaths due to heart disease and 51% of deaths due to stroke [11, 12]. High BP is the leading risk factor in the world especially in the non-industrialized countries [13]. In fact there is some increase in cardiovascular risk in patients with BP 120–140/80–90 (i.e. pre-hypertension) than in those with BP less than 120/80 (i.e. normal BP) even in the general population [14]. Untreated BP <120/<80 mmHg (i.e. normal

levels.

178 Diabetes and Its Complications

strategies [7–10].

(**Figure 1**).

**2.1. High blood pressure (BP)**

BP) is considered as one of the ideal health factors for cardiovascular health [7, 8]. Programmes for controlling high BP in the industrialized countries achieved significant reduction in CVD mortality [7], and tobacco smoking including the second-hand smoke became the leading risk factor [13]. In many non-industrialized countries, such programmes have mostly not been accomplished. As a matter of fact in many such countries due to the inadequate network of the State supported rural and urban health centers/clinics, people often have limited access to blood pressure monitoring and management [15]. It is difficult for the people to regularly visit private clinics or to wait at the long queue in the free medical clinics of public hospitals. In such situations, the patients are more likely to visit hospitals late for crisis management only when the complications (like stroke, coronary heart diseases, kidney failure or pneumonia) develop [15].

#### **2.2. Interaction of high blood pressure and glucose intolerance**

Death rate due to CVD, even in the industrialized countries, seems to be on increase again particularly in the relatively younger population [8]. The emerging epidemic of glucose intolerance, another CVD risk factor, seems to be adding up and interplaying with high BP. Among more than 3000 Euro Heart Survey patients with acute and elective coronary heart diseases, only about one-fourth had normal plasma glucose by the WHO criteria [16]. If the American Diabetes Association classification with fasting plasma glucose >5.6 mmol/L (>100 mg/Dl) had also been considered, the proportion of patients with glucose intolerance would perhaps have been more, as reported in another study in patients with acute coronary insufficiency [17]. There are two pertinent points to note in the interaction between high BP and glucose intolerance.

Firstly, hypertension is relatively more common in people with diabetes, about two times more in one study [18], than in those with normal plasma glucose. More than 75% of adults with diabetes have blood pressure (BP) levels ≥130⁄80 mmHg or are using antihypertensive medication [12]. Secondly, the adverse effects of higher blood pressure are more in people with glucose intolerance than in those with normal blood glucose. Even among people with systolic BP between 120 and 139 mmHg (i.e. at pre-hypertension level), CV mortality rate is about three times more in those with diabetes than in those without diabetes. And the risk is similarly high in different systolic BP ranges from normal to high levels [19]. Mortality is indeed increased 7.2-fold when hypertension is present in patients with diabetes [12]. Lowering 4 mmHg of systolic BP is more effective in reducing cardiovascular events than reducing 1 mmol/L of LDL cholesterol and is about four times more effective than lowering 0.9% of glycated hemoglobin (HbA1c), and thus, in diabetes, BP control is more efficacious and more easy than lowering glucose [20].

or more of moderate-to-vigorous intensity physical activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity) is applicable to most adults and help to achieve cardiovascular fitness and other benefits. Brisk walking can be regularly included into the daily life. Two to three sessions/week of resistance exercise on non-consecutive days are also recommended [25]. Increased physical activity is effective in preventing diabetes, and the protective benefit is especially pronounced in persons at the highest risk for the disease [26]. At higher BMI, exercise is protective against diabetes and is dose-dependent. The prevention of diabetes and reduction of hyperglycemia in diabetes occur even without significant weight reduction [27]. American Diabetes Association recommends that prolonged sitting should be interrupted every 30 minutes for blood glucose benefits, particularly in adults with type 2 diabetes [25]. Possible physical activity even while seated (e.g. by leg exercise with or without sit down leg exercise machines) may also help. A more intensive physical activity program including at least 275 minutes per week may be needed to assist weight loss and avoid regain [21]. Higher levels of physical activity before pregnancy or in early pregnancy are associated with a significantly lower risk of developing gestational diabetes mellitus [28]. NICE guideline recommends women with gestational diabetes to take regular exercise (such as walking for 30 minutes after a meal) to improve blood glucose control [29]. **Figure 2** summarizes the potential benefits of regular physical activity

Principle of Management of Type 2 Diabetes: From Clinical, Public Health…

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and exercise in relation to diabetes.

diabetes and CVD [31].

**Figure 2.** Potential benefits of regular physical activity and exercise in relation to diabetes.

the contents of resting and post-exercise sera may help to elucidate the molecules.

**Research perspective:** Although type 2 diabetic subjects are insulin resistant, they are not resistant to the stimulatory effects of exercise on glucose utilization [30]. The local cellular and other metabolic adaptations could explain the increase in glucose utilization and improvement in the glucose tolerance in exercise and trained muscles. A major challenge has been to elucidate the molecules or cascade of molecules that act through insulin-independent, exercise-stimulated signaling pathway [30]. If such molecules produced during exercise are secreted in the blood and act like hormones in other tissues, organs, muscles and fat, study of the effect in the resting state by the reuse of serum of blood collected during exercise in the same person may give insight into such actions and the difference in

**Research perspective:** Many overweight older people with diabetes have knee osteoarthritis which may prevent them to walk freely. Exercises to strengthen the quadriceps—for example, quadriceps-setting exercise and straightleg raises—are effective in reducing pain and improving function in patients with knee osteoarthritis. However, people often may not adhere to the recommended methods of quadriceps strengthening exercises. Regular exercise with a bicycle ergometer in such patients can have beneficial effects not only for knee osteoarthritis but also for

**Clinical management perspective:** The current guidelines recommend to treat hypertension in type 2 diabetes to an systolic BP target of 130–140 mmHg and a diastolic BP target of 80 mmHg and to consider the lower targets if the patients are younger or when additional CV risk factors or microvascular diseases are present [21]. In the studies, the number of antihypertensive drugs required to achieve the systolic blood pressure around 130–140 mmHg are often more than two and even more than three in many patients. Treatment of hypertension in patients with diabetes is lucidly reviewed in the position paper of American Society of Hypertension [12].

**Public health perspective:** In non-industrialized countries, there is urgent need of establishing the network of the State supported rural and particularly urban health centers/clinics with general practitioners (preferably well trained with residential training in General Practice after medical graduation). It is required (i) for the comprehensive longitudinal health care of the people with diabetes, hypertension, CVD and other conditions, (ii) for supervision of healthcare workers to implement various public health programs including that for hypertension and CVDs and (iii) to provide the State supported diagnostic facilities and antidiabetic, antihypertensive and other CVD drugs and antibiotics (then only it may be possible to restrict the over-the-counter sale of antibiotics and other drugs as the people otherwise would not have any access to such life-saving drugs) [15].

**Research perspective:** Study of the occurrence of CVD complications in the people with pre-hypertension level of BP and impaired glucose intolerance may indicate the different levels of HbA1c and BP to start antihypertensive treatment. The combined presence of the subclinical or borderline hypertension and glucose intolerance (as 'subclinical or borderline syndrome') may be another CVD risk factor, as a residual risk factor of CVDs, at the population level.
