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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 5: Reducing the Risk of Developing Diabetes

Canadian Diabetes Association 2013 Clinical Practice Guidelines

Introduction
  • For the practicing healthcare professional, individualized strategies for diabetes prevention will usually be sought over group- or population-based strategies.
  • Given the increasing incidence and prevalence of diabetes, development of safe and cost-effective interventions to reduce the risk of diabetes are needed to help decrease the burden of diabetes on individuals and the healthcare system.
Reducing the Risk of Developing Type 1 Diabetes
  • Type 1 diabetes is a chronic autoimmune condition characterized by destruction of pancreatic beta cells. The causes are multifactorial, with both genetic and environmental factors playing a part. The exact nature of causative environmental factors continues to be debated.
  • There is a long preclinical period before the onset of overt symptoms, which may be amenable to intervention.
  • Immunotherapeutic interventions continue to be the main focus of disease prevention (primary prevention).
    • Preliminary studies have been performed and have yielded mixed results. Further research is needed in this area.
  • Enhancement of “regulatory” immune mechanisms currently shows the most promise in terms of slowing the progression of the disease and preserving beta cell mass (secondary prevention).
    • This strategy tries to halt, at the time of diagnosis, the immune-mediated destruction of beta cells so as to preserve any residual capacity to produce insulin.
    • Progress in this field has been slow due to important ethical considerations.
  • As safe and effective preventive therapies have not yet been identified, any attempts to prevent type 1 diabetes should be undertaken only within the confines of formal research protocols.
Reducing the Risk of Developing Type 2 Diabetes
  • Preventing type 2 diabetes may result in significant public health benefits, including lower rates of cardiovascular disease (CVD), renal failure, blindness and premature mortality.
  • Primary approaches to preventing diabetes in a population include the following:
  1. programs targeting high-risk individuals (such as those with impaired glucose tolerance [IGT] or obesity);
  2. programs targeting high-risk subgroups, such as high-risk ethnic groups;
  3. programs for the general population, such as those designed to promote physical activity and healthy eating in adults or children.
  • Variables associated with the subsequent development of type 2 diabetes include older age, certain ethnic backgrounds, obesity (especially abdominal obesity), physical inactivity, history of gestational diabetes mellitus, overt coronary artery disease, high fasting insulin levels and IGT.
  • Results of large, well-designed studies assessing lifestyle and pharmacological interventions in adults to prevent the progression from IGT to diabetes have been published.
  • No pharmacological agent is approved for diabetes prevention in Canada.
Lifestyle
  • Changes in lifestyle were assessed in the Finnish Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP).
    • These studies focused on dietary modification that targeted a low-calorie, low-fat, low-saturated fat, high-fibre diet and moderate-intensity physical activity.
    • In both studies, the risk reduction for diabetes was 58% at 4 years. Participants in the DPP were offered further lifestyle interventions for a median of 5.7 more years and benefits were sustained for up to 10 years.
  • A structured program of lifestyle modification that includes moderate weight loss and regular physical activity should be implemented to reduce the risk of type 2 diabetes in individuals with IGT [Grade A, Level 1A], and IFG [Grade B, Level 2] and A1C 6.0%–6.4% [Grade D, Consensus].
Pharmacotherapy

Metformin

  • Metformin was used in a second arm of the DPP and results suggested that 26% of the diabetes prevention effect could be accounted for by its pharmacological action.
    • Even after a washout period, the incidence of diabetes was still reduced by 25%.
    • Metformin did not have a significant effect in the older age group (≥60 years) and in less obese subjects (BMI <35kg/m 2).
  • In individuals with IGT, pharmacological therapy with metformin may be used to reduce the risk of type 2 diabetes [Grade A, Level 1A].

Thiazolidinediones

  • Studies to determine the effects of thiazolidinediones on the delayed development of diabetes include the troglitazone arm of the DPP, the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial and the Actos Now for the Prevention of Diabetes (ACT NOW) study (pioglitazone).
  • Despite the favourable effects of thiazolidinediones on delaying the development of type 2 diabetes, the multiple potential adverse effects makes it difficult to recommend its widespread use in IFG or IGT.

Combination therapy

  • The combination of metformin 500 mg twice daily and rosiglitazone 2 mg twice daily was found to reduce the progression to diabetes by 66% (95% CI 41–80) among 103 people with IGT compared to 104 people randomized to placebo over a median of 3.9 years.

Alpha-glucosidase inhibitors

  • The Study to Prevent Non-Insulin Dependent Diabetes (STOP-NIDDM) used acarbose 100 mg tid in a 5-year study with a mean follow-up of 3.3 years.
    • There was a 25% to 36% reduction in the risk of progression to diabetes, depending on whether the diagnosis was based on 1 or 2 oral glucose tolerance tests (OGTT). This beneficial effect was not affected by age or BMI.
    • When the drug was discontinued, the effect of acarbose did not persist.
    • In this IGT population, acarbose treatment was also associated with a 49% reduction in CV events (p=0.032).
  • In individuals with IGT, pharmacotherapy with acarbose may be used to reduce the risk of type 2 diabetes [Grade A, Level 1A].

Orlistat

  • The Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) study examined the effect of orlistat in combination with an intensive lifestyle modification program (diet and exercise) on the prevention of diabetes in obese individuals.
    • Compared to placebo, orlistat treatment resulted in significantly more weight loss (5.8 vs. 3 kg; p<0.001) and a further 37% reduction in the incidence of diabetes.
    • However, the study results were affected by important methodological limitations, including a very high dropout rate.

Incretin-based therapies    

  • Liraglutide has been shown to effectively prevent IGT conversion to type 2 diabetes and cause reversion to normoglycemia.
    • In a 20-week study, liraglutide was administered to 564 obese individuals who did not have diabetes, 31% of whom had IGT.
    • Subjects were randomized to 1 of 4 liraglutide doses (1.2 mg, 1.8 mg, 2.4 mg, or 3.0 mg), placebo, or orlistat three times daily.
    • A1C was reduced by 0.14% to 0.24%. The prevalence of prediabetes decreased by 84% to 96% with liraglutide 1.8 mg, 2.4 mg and 3.0 mg doses.
Diabetes prevention in high-risk ethnicities
  • Ethnic groups such as South Asians, Hispanics and Aboriginals, are at very high risk for and have a high prevalence of type 2 diabetes (12%–15% in the Western world). Reasons for this include genetic susceptibility, altered fat distribution and higher prevalence of metabolic syndrome.
  • Many from high-risk ethnicities develop diabetes at a younger age and often have complications at the time of diagnosis due to long-standing, preexistent diabetes. As a result, there may be a benefit of delaying the onset of diabetes in this population.
  • The Indian Diabetes Prevention Programme studied the prevention of diabetes with both lifestyle and pharmacological interventions where the progression to diabetes from IGT was quite high (55%) over 3 years. It found that lifestyle modification and metformin prevent type 2 diabetes in Asian subjects with IGT (IDPP-1).
  • This approach to prevention may lead to cost savings, fewer complications and lower morbidity, but it remains to be proven with hard clinical endpoints. Lifestyle measures not only reduce the risk of diabetes but have other health benefits, so the overall benefit is positive with little harm.
  • These measures of prevention must be delivered in a culturally sensitive manner to these populations.


For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, including references, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 5.