Prevention of Diabetes

Peter Schwarz, Prasuna Reddy, Peter Schwarz, Prasuna Reddy

• Publisher: Wiley-Blackwell
• Year: 2013
• ISBN:
  9781118661314
• Edition: 1
• Topic: Medicine
• Subtopic: Public Health, Administration & Care

Expertly authored by the world's leading specialists in the field, Prevention of Diabetes is the definitive guide for better preventative diabetes care.

Using an evidence-based approach, it outlines the very latest in the identification of people at high risk for type 2 diabetes and how best to use interventional methods such as screening at-risk individuals, pharmaceutical intervention and lifestyle changes.

In addition, it will provide healthcare professionals with the clinical knowledge required to clearly identify the early symptoms of diabetes, enabling them to provide their patients with better clinical care and helping avoid the onset of full-blown diabetes.

Also covered are both the health economics of establishing, and the methods of implement/delivering targeted prevention programmes into clinical and health care practice, based on the vast experience of the editors due to their involvement in such programmes.

Prevention of Diabetes provides clear and expert information in a practical, accessible way, and is ideal reading for all those with an interest in the prevention of diabetes and obesity, such as public health workers, specialists in diabetes and obesity, and GP's seeing patients with early onset or pre-diabetes symptoms.

CHAPTER 1

What have we learned from the number of clinical trials?

Jaana Lindström

Department of Chronic Disease Prevention, Diabetes Prevention Unit, National Institute for Health and Welfare (THL), Helsinki, Finland

Introduction

The primary prevention of type 2 diabetes (T2D) was originally proposed by Dr. E. Joslin in 1921 [1]. He commented on how obese people are more likely to have diabetes than their slimmer neighbors. Indeed, to be able to prevent a chronic disease such as T2D it is necessary to have knowledge about its modifiable risk factors and natural history. Furthermore, there should be a preclinical phase or a “window of opportunity” for intervention as well as a feasible screening tool to identify high-risk individuals. In addition, the efficacy of the intervention has to be proven in a clinical trial setting.

T2D is a very expensive disease – about 10–15% of the total health care costs in developed countries are spent to treat T2D and, in particular, its complications [2,3]. To avoid late complications of T2D and related costs, prevention of T2D itself is therefore desirable. There are some “natural” experiments in which ethnic groups have experienced rapid westernization and with it a rapid increase in the rates of obesity and T2D [4]. Therefore it is logical to assume that by reversing these lifestyle changes it would be possible to prevent the development of the disease. Such a potential for reversibility has been shown among Australian Aboriginals [5]. In these experiments hyperglycemic people returned to living in a traditional hunter–gatherer way of life – an ultimate lifestyle change not suitable for everybody.

T2D develops as a result of complex multifactorial process with both lifestyle and genetic origins. The main risk factors for T2D are obesity and a sedentary lifestyle [6]. A “westernized” dietary pattern with low fiber [7–9] and high saturated [10] and trans fats [11], refined carbohydrates [12], sweetened beverages [13], sodium [14], and red meat and processed meat products [15,16] intake has been shown to be associated with increased T2D risk. Another feature of modern lifestyle, voluntary sleep deprivation, also increases diabetes risk [17,18]. Protective lifestyle factors, in addition to those mentioned above, include coffee [19–21] and moderate alcohol, particularly wine consumption [22].

Impaired glucose tolerance (IGT) is a hyperglycemic state between normoglycemia and T2D, diagnosed by a 2-h oral glucose tolerance test (OGTT). Of the people with IGT, approximately half will develop T2D during a 10-year follow-up period [23,24]. In Asian populations the rate of progression seems to be even faster [25,26]. It is well known that the risk of complications begins in the prediabetic phase prior to glucose levels reaching diagnostic cut-points for T2D [27–29]. People with IGT would thus be the perfect subjects for preventive interventions.

Major lifestyle trials in prevention of T2D

Da-Qing Study

A large population-based screening program (110 660 persons screened with OGTT) to identify people with IGT was carried out in Da-Qing, China, in 1986 [25,30]. The randomization of study subjects was not random, but the 33 participating clinics (= cluster randomization) were randomized to carry out the intervention according to one of the four specified intervention protocols (diet alone, exercise alone, diet–exercise combined, or none). Altogether, 577 (312 men, 264 women + 1 undefined) subjects with IGT participated in the trial, and of these 533 participated in the measurements at the end of the intervention in 1992. The cumulative 6-year incidence of T2D was lower in the three intervention groups (diet alone, exercise alone, diet–exercise combined; 41–46%) than the control group (68%). Because no individual allocation of study subjects to the intervention and control groups was done, the results based on individual data analysis must be interpreted with caution. The study subjects were relatively lean, with a mean body mass index (BMI) of 25.8 kg/m², but, despite that, the progression from IGT to diabetes was high; more than 10% per year in the control group.

In clinics assigned to dietary intervention, the participants were encouraged to reduce weight if their BMI was >25 kg/m², aiming at <24 kg/m², otherwise a high carbohydrate (55–65 energy proportion (E%)) and moderate fat (25–30E%) diet was recommended. Participants were encouraged to consume more vegetables, reduce simple sugar intake, and control alcohol intake. Small group counseling sessions concerning diet and/or physical activity were organized weekly for the first month, monthly for 3 months, and every 3 months thereafter. Participants also received individual counseling by physicians. The participants were encouraged to increase their level of leisure time physical activity by at least 1–2 “units” per day, one unit corresponding to 30 minutes of slow walking, shopping, house cleaning, or traveling by bus, 20 minutes of cycling or ballroom dancing, 10 minutes of slow running, climbing stairs, or disco dancing, or 5 minutes of swimming, jumping rope, or playing basketball.

The overall changes in risk factor patterns were relatively small. Body weight did not change in lean subjects, and there was a modest, <1 kg, reduction in subjects with baseline BMI >25 kg/m². The estimated changes in habitual dietary nutrient intakes were small and nonsignificant between groups. Within the exercise and diet plus exercise groups, physical activity increased modestly but statistically significantly (+ 0.6–0.8 activity units per day on average). Thus, it is not easy to determine the factors responsible for the beneficial effects on the risk of T2D. In this population, weight control obviously was not the key issue. Physical activity and qualitative changes in diet that are difficult to measure on individual level probably played a key part.

The 20-year follow-up of the original study cohort [30] showed that the reduction in diabetes incidence persisted in the combined intervention group compared with control participants with no intervention, and, furthermore, the risk reduction remained essentially the same during the post-intervention period. It should be noted that diabetes incidence during the follow-up was high: in the final analyses 80% of the intervention participants and 93% of the control participants had developed diabetes. The follow-up analyses showed no statistically significant differences in cardiovascular disease (CVD) events, CVD mortality, or total mortality between the control group and the combined intervention groups. A nonsignificant 17% reduction in CVD death was observed, which can be seen to be at least suggestively in favor of the lifestyle intervention.

Finnish Diabetes Prevention Study

The intervention of the Finnish Diabetes Prevention Study (DPS) was carried out during 1993–2001 in five clinics in Finland, aiming to prevent T2D with lifestyle modification alone [24,31–33]. A total of 522 individuals at high risk of developing diabetes were recruited into the study, mainly by screening for IGT in middle-aged (age 40–64 years) overweight (BMI >25 kg/m²) subjects. The presence of IGT before randomization was confirmed in two successive 75-g OGTT; the mean of the two values had to be within the IGT range to qualify for the study. The participants were randomly allocated either into the control group or the intensive intervention group. The subjects in the intervention group had frequent consultation visits with a nutritionist (seven times during the first year and every 3 months thereafter). They received individual advice about how to achieve the intervention goals which were reduction in weight of 5% or more, total fat intake <30% of energy consumed, saturated fat intake <10% of energy consumed, fiber intake of at least 15 g/1000 kcal, and moderate exercise for 30 minutes per day or more. Frequent consumption of wholegrain cereal products, vegetables, berries and fruit, low-fat milk and meat products, soft margarines, and vegetable oils rich in monounsaturated fatty acids were recommended. The dietary advice was based on 3-day food records completed four times per year. The participants were also individually guided to increase their level of physical activity. Endurance exercise (walking, jogging, swimming, aerobic ball games, skiing) was recommended to increase aerobic capacity and cardiorespiratory fitness. Supervised, progressive, individually tailored circuit-type resistance training sessions to improve the functional capacity and strength of the large muscle groups were also offered.

The control group participants were given only general advice about healthy lifestyle at baseline. An OGTT was carried out annually for all participants and if either fasting or 2-h glucose values reached diabetic levels a confirmatory OGTT was performed. The study end-point was only recorded if the second test also reached diabetic levels; otherwise the subjects continued with their randomized treatment.

Body weight reduction from baseline was on average 4.5 kg in the intervention group and 1.0 kg in the control group subjects (P < 0.001) after the first year and at 3 years, weight reductions were 3.5 and 0.9 kg (P < 0.001), respectively. Indicators of central adiposity and glucose tolerance improved significantly more in the intervention group than in the control group at both 1-year and 3-year follow-up examinations. At the 1-year and 3-year examinations intervention group subjects reported significantly more beneficial changes in their dietary and exercise habits, based on dietary and exercise diaries.

After 4 years the cumulative incidence of diabetes was 11% (95% CI 6–15%) in the intervention group and 23% (95% CI 17–29%) in the control group. Based on life-table analysis, the risk of diabetes was reduced by 58% (P < 0.001) during the trial in the intervention group compared with the control group during a mean follow-up time of 3.2 years. The absolute risk reduction was 12% at that point and the number needed to treat (NNT) was 8. Both men and women benefited from lifestyle intervention: the incidence of diabetes was reduced by 63% and in women by 54% in the intervention group compared with the control group. None of the people (either in the intervention or control group) who had succeeded in achieving all five predefined lifestyle targets developed diabetes, while approximately one-third of the people who did not reach a single one of the targets developed T2D. This is direct empirical proof that the reduction of the diabetes risk was indeed mediated through the lifestyle changes. Post hoc analyses have also shown that both dietary changes – adopting a diet with moderate fat and high fiber content [34] – as well as increasing physical activity [35] were independently associated with diabetes risk reduction. Furthermore, a subgroup analysis with intravenous glucose tolerance testing (n = 87 at baseline and 52 at 4-year examination) showed improvement in insulin resistance which was highly correlated with achieved body weight reduction [36]. The effect of lifestyle intervention on diabetes incidence was shown to be the largest among the oldest age group and those with the highest baseline risk profile, as measured with the Finnish Diabetes Risk Score (FINDRISC) [37].

An analysis using the data collected during the extended follow-up of the DPS revealed that after a median of 7 years' total follow-up a marked reduction in the cumulative incidence of diabetes was sustained [24]. The relative risk reduction during the total follow-up was 43%. The effect of intervention on diabetes risk was maintained among those who after the intervention period were without diabetes: after median post-intervention follow-up time of 3 years the corresponding incidence rates were 4.6 and 7.2 per 100 person-years, respectively (log-rank test P = 0.0401), that is, 36% relative risk reduction.

The 10-year follow-up results on the effect of DPS lifestyle intervention on total mortality and cardiovascular morbidity were published in 2009 [38], based on register linkage of the original study cohort to the national Hospital Discharge Register and Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person-years) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person-years) were similar in the intervention and control groups. Interestingly, when the DPS intervention and control groups together were compared with a population-based cohort including people with IGT, adjusted hazard ratios were 0.21 (95% CI 0.09–0.52) and 0.39 (95% CI 0.20–0.79) for total mortality and 0.89 (95% CI 0.62–1.27) and 0.87 (95% CI 0.60–1.27) for cardiovascular morbidity. Thus, the risk of death among the DPS participants was markedly lower than in a population-based IGT cohort.

Diabetes Prevention Program

The Diabetes Prevention Program (DPP) [39,40] was a multicenter randomized clinical trial carried out in the United States. It compared the efficacy and safety of three interventions: an intensive lifestyle intervention or standard lifestyle recommendations combined with metformin or placebo. The study focused on high-risk individuals (n = 3234) with IGT who also had slightly elevated fasting plasma glucose (>5.5 mmol/L). The main results were intensive lifestyle intervention reduced T2D risk after 2.8 years' mean follow-up by 58% compared with the placebo control group. Lifestyle intervention was also shown to be superior to metformin treatment (850 mg twice daily) which led to T2D risk reduction of 31% compared with placebo [39].

The lifestyle intervention in DPP was primarily carried out by special educators, “case managers” and was relatively intense. The lifestyle intervention commenced with a 16-session structured core curriculum within t...

Table of contents

• Cover
• Title page
• Copyright page
• Contributors
• Preface
• CHAPTER 1: What have we learned from the number of clinical trials?
• CHAPTER 2: Identification of target populations for intervention
• CHAPTER 3: Diagnosis of prediabetes and diabetes prevention
• CHAPTER 4: What do we know about recruitment and retention in diabetes prevention programs? An Australian perspective
• CHAPTER 5: Depression and diabetes prevention
• CHAPTER 6: Diabetes prevention in a challenging environment
• CHAPTER 7: Global migration and prevention of diabetes
• CHAPTER 8: Diabetes prevention in practice: examples from the real world
• CHAPTER 9: Quality management and outcome evaluation in diabetes prevention
• CHAPTER 10: Training of prevention managers
• CHAPTER 11: Prevention of type 2 diabetes: the role of physical activity
• CHAPTER 12: Overview: Potentials of new media for the training of health educators in the field of diabetes prevention
• CHAPTER 13: Practical approach to the implementation of diabetes prevention
• Index