Lifestyle Interventions for the Prevention of Type 2 Diabetes Mellitus

Identifying People at Risk

The question of who should be targeted for diabetes risk reduction is not easy to answer because the effect of an intervention program to prevent T2DM in adulthood depends on the setting where the intervention is performed, the effectiveness of the intervention in addressing the high-risk individual, accessibility and affordability, and a variety of additional variables. However, the main considerations when deciding who should be targeted for T2DM prevention are the effectiveness and affordability of the interventions available after the high-risk person has been identified. Screening for diabetes risk makes no sense without availability of a successful and sustainable intervention program. Interventions can have various approaches, strategies, and concepts. Furthermore, strategies for targeting people at high risk will vary significantly among different settings and different population groups. The risk factors for T2DM are well recognized, and T2DM is often preceded by a period of IGT that is characterized by increasing insulin resistance and beta cell dysfunction. Visceral obesity plays a key role in triggering the development of insulin resistance and increasing T2DM risk. It is also recognized that many people with T2DM remain undiagnosed and that patients with long diagnostic delays often have significant complications at diagnosis. This suggests that combined screening for both IGT and undiagnosed prevalent T2DM could be a pragmatic option. Indeed, data show that screening for both conditions together is cost-effective, particularly when lifestyle and pharmacologic interventions are then used to delay the onset of T2DM in high-risk individuals. Screening for T2DM and IGT in high-risk populations is now recommended by a number of international diabetes associations ; a plethora of tools are available to identify people at increased risk of T2DM, and there is little evidence of long-term, physical or psychological harm from such screening.

The consensus (based on screening approaches used in practice in the United States, Germany, Australia, Finland, the United Kingdom, and other countries) ^, seems to favor a targeted, staged approach with the first step being to identify those at high risk and a second step being to confirm glycemic status (whether T2DM, IGT, or normoglycemia). Preliminary data about this broad approach suggest that it is more cost-effective to use a noninvasive screening tool as the first stage in screening rather than a blood test. Risk scores tend to be based around risk factors such as age, gender, body mass index (BMI), ethnicity, family history of diabetes, and the use of antihypertensive medication. Risk scores have been shown to have good sensitivity and specificity for identifying diabetes risk. For example the Finnish Diabetes Risk Score (FINDRISC), the Danish Risk Questionnaire, the Cambridge Risk Score, the Leicester Diabetes Risk Score, and the Indian Score have all been associated with a sensitivity of 76% to 77% and specificity of 55% to 72%, with a positive predictive value varying from 7% to 11%. The most common approach used is the FINDRISC questionnaire, which individuals use to self-assess their risk based on seven questions; FINDRISC has been shown to have good validity at predicting future diabetes over a 10-year period. It is important to note that although FINDRISC has been validated for use in various countries, given the varying profile and prevalence of risk factors in different settings, the score performance cannot be generalized from one country to another. It is therefore important that risk scores be validated in the population in which they will be applied. The other approach is to use data that are routinely available to the general practitioner (e.g., the Cambridge Risk Score, the QDScore, the Leicester Practice Risk Score).

The second stage involves diagnostic testing. In practice, this usually consists of either a fasting glucose or a hemoglobin A1c (HbA1c) test, although oral glucose tolerance testing can also be used. A recent statement by the International Expert Committee of the World Health Organization (WHO) has advocated that an HbA1c of 6.5% (48 mmol/mol) or higher can now be used to define T2DM. However, there is no clear consensus on how or whether HbA1c should be used to classify diabetes risk below this level. The American Diabetes Association (ADA) tentatively suggested that an HbA1c value of 5.7% to 6.4% indicates a high risk of T2DM, whereas an international expert committee suggested a range of 6.0% to 6.4%. ^, The latter range was also recently endorsed by the National Institute for Health and Care Excellence (NICE) in the United Kingdom, which now recommends that HbA1c be used to identify those with a high risk of T2DM and that patients with a value of 6.0% to 6.4% be referred to a T2DM prevention program. Prospective data from the United Kingdom support the use of 6.0% to 6.4% to define an at- risk category, because individuals in this group were found to have a risk of future T2DM that was twice that in individuals with a value of 5.5% to 5.9%. However, other data from Germany suggest that an HbA1c threshold of 5.7% is likely to have the best sensitivity and specificity for detection of future T2DM risk but demonstrate that the combination of HbA1c and the 1-hour plasma glucose concentration after a 75-g oral glucose load in predicting future T2DM risk was significantly better in a multivariable model than either one of them alone. The 1-hour plasma glucose concentration has previously been shown to be a strong predictor of T2DM risk and also other chronic disease but has major logistical issues. Furthermore, the optimal HbA1c cut point for identifying individuals at increased diabetes risk is 5.7% and not 6.0% as originally suggested by the ADA Expert Committee. If HbA1c exceeding 6.0% had been used to identify individuals at increased risk for future T2DM, only about one third of patients who developed T2DM would have been identified. Thus, use of an HbA1c cut point of 5.7% together with the 1-hour plasma glucose concentration would identify many additional high-risk individuals who could benefit from an intervention program.

The most cost-efficient way to balance resources against risk has yet to be determined. In the meantime, the balance that is struck may depend to a large extent on pragmatic considerations, particularly financial constraints. It is acknowledged that, along with strategies for identification and intervention for those with a high risk of a widely prevalent condition such as T2DM, it is also fundamentally important to use initiatives that are aimed at shifting the distribution of known risk factors, such as BMI in adults or BMI percentiles in childhood and waist circumference within the population as a whole. Strategies for primary prevention on a public health level and high-risk strategies need to work in parallel.

Physical Activity

Epidemiologic, experimental, and randomized controlled clinical study trial-level evidence has consistently demonstrated that levels of physical activity are centrally involved in the regulation of glucose homeostasis, independent of other factors including adiposity. ^, A modest increase in walking activity, toward levels that are consistent with the minimum recommendations, significantly improved 2-hour postload glucose levels by 23 mg/dL over 12 months in high-risk overweight and obese individuals despite the absence of any significant change in body weight or waist circumference. This may correspond to a greater than 60% reduction in risk of developing T2DM within 24 months. These findings were consistent with findings from other studies, but replication of the results is needed and attempts are under way. Although the promotion of physical activity is a cornerstone of effective T2DM prevention programs, the role of physical inactivity in helping identify T2DM risk is less clear and more problematic for several reasons. First, physical inactivity is highly prevalent among the general population; it has consistently been shown that 50% to 80% of the population in both developed and developing countries fails to meet the minimum recommendations for health. Indeed, when physical activity levels are objectively measured, rather than by subjective self-report, around 95% of the population fail to meet the minimum requirements for health, making inactivity a near universal condition. Therefore commonly used definitions of physical inactivity do not provide a clear mechanism for stratifying diabetes risk. Second, methods that rely on self-reporting by individuals of their activity levels are highly inaccurate and unreliable. For example, an internationally used and validated self-reported measure of physical activity described as little as 10% of the variation in objectively measured levels through accelerometry ; in contrast, simple measures of adiposity, such as BMI and waist circumference, are reasonably accurate on a population level. For these reasons, self-recording levels of physical (in)activity has not been shown to add to the predictive power of diabetes risk scores or to be useful when incorporated into other methods of quantifying diabetes risk. However, it is important that physical inactivity, as with other lifestyle variables, be considered for the individual assessments of T2DM risk.

To be successful, lifestyle intervention programs should focus on types of physical activity that are acceptable to most of the population. Walking has consistently been shown to be the most popular choice of physical activity, including in those with a high risk of T2DM. Indeed, walking for 150 min/wk during leisure time is associated with a 60% reduction in the relative risk of T2DM compared with those that did little or no walking in their leisure time. Of importance, walking is associated with fewer barriers than other forms of physical activity in black and minority ethnic populations dwelling in developed countries, such as South Asians.

Wearing a pedometer and keeping a daily step log have been widely advocated as effective self-regulatory strategies in the promotion of increased ambulatory activity, and their use has consistently been shown to successfully promote increased physical activity. The success of pedometer interventions is centered on the pedometer's ability to raise awareness of current activity levels, provide objective feedback to the individual, and facilitate clear and simple goal setting. To be effective, it is essential that realistic and personalized step-per-day goals be used; goals that are too ambitious can often be demotivating and lead to failure. Sedentary individuals (fewer than 5000 steps/day) should initially aim for an average increase in ambulatory activity of around 2000 steps/day conducted at a moderate to vigorous intensity, which is roughly equivalent to an additional 150 minutes of walking activity per week. Alternatively, the categories of ambulatory activity shown in Table 5-1 can be used to guide lifestyle interventions. For example, those in the sedentary or inactive categories could initially aim to increase their ambulatory activity by at least 2000 steps/day. Those in the moderate category could be encouraged to try and enter the high category, and those achieving the high or very high categories should be helped to at least maintain their activity levels. For people who have significant barriers to walking, such as joint problems, alternative forms of physical activity, such as cycling, water aerobics, or swimming, should be encouraged.

Nutritional Aspects

Obesity is one of the most important risk factors for T2DM, and population trends in obesity and T2DM run in parallel. The pathophysiology of adiposity with regard to the development of T2DM is not fully understood; however, several mechanisms that may interact have been identified. Adipose tissue, especially the tissue surrounding internal organs (visceral fat), is today regarded as an active endocrine organ that secretes a variety of proinflammatory adipokines that act at both the local and the systemic levels. Cornier and colleagues have reported that increasing adipose tissue mass leads to changes in the secretion of these adipokines as well as increased turnover of free fatty acids, which bring on insulin resistance, the harbinger of metabolic disturbances leading to T2DM.

Even though the basic cause of excess body fat accumulation is an imbalance between energy intake (i.e., dietary intake) and expenditure, the factors predisposing to the development of overweight and obesity are multifactorial and poorly understood. Nevertheless, regular physical activity, high dietary intake of fiber, and reduced intake of energy-dense micronutrient-poor foods were identified by WHO as lifestyle targets for reducing obesity. In the DPS, the dietary energy density was found to be associated with achieved weight reduction, which supports the intuitive recommendation to increase foods with low energy density such as vegetables and fruits to increase satiety while reducing total energy intake. An increased understanding of these mechanisms will be helpful in providing prioritization of behavioral targets for future prevention programs.

The Right Intervention for the Person at Risk