Davidson uses data from the DPP metformin washout study and from the Diabetes Prevention Program Outcomes Study DPPOS to argue that because metformin may not cause long-lasting changes in the pathophysiology of prediabetes, it should not be used for diabetes prevention.

We disagree with this argument. Antihypertensive and lipid-lowering therapy are effective only so long as they are continued. No one would argue that they should not be used because their effects on blood pressure and cholesterol disappear when treatment is discontinued.

The complications and comorbidities of diabetes occur as a function of the degree and duration of hyperglycemia. Computer simulation modeling has demonstrated that metformin delayed the onset of diabetes by 3. Fourth, Dr. Metformin is inexpensive, and economic analyses of the DPP and DPPOS have demonstrated that in an intention-to-treat analysis over 10 years, metformin therapy is cost-saving compared with placebo—that is, it both reduces costs and improves health outcomes It is reasonable to expect that selective use of metformin in individuals with the greatest likelihood of benefit would yield even greater cost savings.

Finally, we would point out that there is a nationwide demand for pharmacotherapy to improve health. population in every age-group reported that they used dietary supplements for their health and wellness benefits Revenues from vitamin and nutritional supplement production in the U. Many of these supplements including cinnamon, chromium, α-lipoic acid, and bitter melon are specifically marketed for diabetes and diabetes prevention.

Allowing the marketing and sale of these unproven therapies for diabetes prevention and denying high-risk individuals metformin, a proven safe, effective, and cost-saving treatment, is wrong.

In conclusion, we believe that metformin should be used to treat prediabetes selectively. The efficacy, safety, and cost-effectiveness of metformin therapy were demonstrated among very high-risk individuals. Assurance of achieving the same beneficial effects is most secure when metformin therapy is prescribed to individuals who meet eligibility criteria for the DPP.

Recognizing the heterogeneity of treatment effect, metformin therapy should also be limited to individuals who are at highest risk and most likely to benefit, including those who are younger, more obese, more hyperglycemic, or who have histories of gestational diabetes mellitus.

We reject Dr. Early use of metformin can delay the emergence of overt but often unrecognized hyperglycemia that causes microvascular and neuropathic complications and is associated with increased cardiovascular risk.

By delaying or preventing the onset of diabetes, metformin therapy is likely to have direct benefits on long-term complications and health-related quality of life. See accompanying article, p. Duality of Interest. is an employee of Virta Health and a consultant for Novo Nordisk. No other potential conflicts of interest relevant to this article were reported.

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Volume 43, Issue 9. Previous Article Next Article. Article Information. Article Navigation. Commentaries August 11 Metformin Should Be Used to Treat Prediabetes in Selected Individuals William H. Herman X. Corresponding author: William H. Herman, wherman umich. This Site.

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Search ADS. Early detection and treatment of type 2 diabetes reduce cardiovascular morbidity and mortality: a simulation of the results of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care ADDITION-Europe.

Before , there were six different criteria for diagnosing diabetes. No FPG criterion for diagnosing prediabetes was offered. The NDDG criteria for diagnosing diabetes were not equally sensitive. The American Diabetes Association ADA convened an Expert Committee to address this imbalance 7.

However, again there was an imbalance. Many fewer people with IFG subsequently developed diabetes compared with those who had IGT. The ADA convened another meeting of the Expert Committee to address this issue 8 , 9. In response, the ADA, the European Association for the Study of Diabetes, and the International Diabetes Federation appointed an International Expert Committee that agreed with the invited expert panel regarding the diagnosis of diabetes if the A1C level were confirmed However, that committee also opined that because of the progressive continuum of risk of increasing glycemia below the diagnostic levels of diabetes for the subsequent development of diabetes, it was inappropriate to define a specific prediabetes risk group.

The ADA subsequently adopted the recommended A1C level for diagnosing diabetes but also included an A1C criterion of 5. The lower bound of the prediabetes criteria was based on modeling the estimated composite risk of developing diabetes and cardiovascular disease CVD using cross-sectional data from the — NHANES However, the glycemia of prediabetes is not independently associated with CVD 14 — Furthermore, in people who experience an acute coronary syndrome, the outcomes length of hospital stay, day readmission rate, acute pulmonary edema, month recurrent acute coronary syndrome, or mortality are no different between those with prediabetes A1C 5.

Rather, the association between prediabetes and CVD is due to the other risk factors for CVD that people meeting the glycemic criteria for prediabetes also have. Restricting the modeling to only the risk for developing diabetes might have influenced the prediabetes A1C criterion.

Although numerous studies have shown that glycemia is not an independent risk factor for CVD 14 — 21 , it certainly is for the development of diabetes. Similarly, the risk with the A1C IEP criterion of 6. Claims have been made that treating people with prediabetes with antihyperglycemic drugs metformin, thiazolidinediones [TZD], α-glucosidase inhibitors, glucagon-like peptide 1 agonists, basal insulin has delayed or even prevented the development of diabetes.

This is a misinterpretation of the situation. These drugs have simply treated a level of glycemia lower than the diagnostic criteria for diabetes retarding its increase to the level at which a diagnosis of diabetes would occur.

After these drugs were discontinued, the prevalence of diabetes in treated individuals mirrored that in the placebo group.

However, the time course of action of a drug is much more related to its tissue biologic effects than to the pharmacokinetics of its concentration in the blood. It is well established that it takes 2—4 weeks for both metformin and sulfonylureas to exert their maximal effects when started 33 — Although the author could find no studies examining the time course of the effect of metformin wearing off, it takes 2—4 weeks for the effect of a sulfonylurea tolazamide to completely dissipate Troglitazone, a TZD that was removed from the market because of hepatic toxicity, was used for a mean of 0.

In those who had not developed diabetes during the intervention period, the rate of development of diabetes was the same in both groups during the 2- to 3-month washout period after both rosiglitazone and its placebo were discontinued 39 and 1.

The Outcome Reduction With Initial Glargine Intervention ORIGIN study compared people with CVD risk factors who also had IFG, IGT, or early type 2 diabetes and who were given either glargine insulin or placebo The pathophysiologic abnormalities of insulin resistance and progressive β-cell dysfunction that characterize prediabetes were not fundamentally altered by these drug treatments 42 , 43 , which explains the lack of any long-term effects when these medications were discontinued Even so, should metformin treatment be offered to individuals whose glycemic parameters are near the diagnosis for diabetes, i.

There are three arguments against this. Second, approximately one-third of people with prediabetes return to normal glucose regulation NGR.

After the study ended, the percent of participants who returned to NGR 1. Third, as described previously, the diagnostic criteria for diabetes were selected because the risk for microvascular complications increased beyond that level of glycemia. Metformin, the preferred initial drug for treating patients with diabetes, is started to lower glycemia to levels that are not associated with this risk.

Five studies 51 — 55 have shown that the development or progression of retinopathy and microalbuminuria over a 6- to year period was almost nil if A1C levels were kept below 7. So, given that two-thirds of people with prediabetes do not develop diabetes over many years 45 — 47 , and in approximately one-third glycemia returns to normal 40 , 45 , 47 — 50 , why put people who are not at risk for the microvascular complications of diabetes when prediabetes is diagnosed on a drug possibly for the rest of their lives that has no immediate advantage except to lower subdiabetes glycemia to even lower levels?

This Perspective is not arguing against the benefit of delaying the development of diabetes. Rather, it is pointing out that the benefit of delay achieved with medication must be weighed against the potential adverse effects of the drug, its cost, and the important fact that a large number of people with the diagnosis of prediabetes will not develop diabetes and metformin would be of no benefit for them.

The argument is that lifestyle interventions, especially weight loss in overweight and obese individuals, should be pursued rather than use of a medication.

It seems more prudent to identify individuals at the highest risk for developing diabetes—i. Meanwhile, these individuals should be intensely counseled on lifestyle interventions to reduce the risk of developing diabetes, and the risk factors for CVD should be aggressively addressed.

See accompanying article, p. Duality of Interest. No conflicts of interest relevant to this article were reported. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search.

User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 43, Issue 9. Next Article. Article Information. Article Navigation. Perspectives in Care August 11 Metformin Should Not Be Used to Treat Prediabetes Mayer B. Davidson Charles R.

Drew University, Los Angeles, CA. Corresponding author: Mayer B. Davidson, mayerdavidson cdrewu. This Site. Google Scholar. Diabetes Care ;43 9 — Article history Received:. Connected Content. A commentary has been published: Metformin Should Be Used to Treat Prediabetes in Selected Individuals.

Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Diabetes Prevention Program Research Group.

Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.

Search ADS. More evidence for a prevention-related indication for metformin: let the arguments resume! Centers for Disease Control and Prevention. National Diabetes Statistics Report, Department of Health and Human Services. Accessed 2 February National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance.

Clinical irrelevance of the current diagnostic criteria for abnormal carbohydrate metabolism in asymptomatic individuals.

Restricting the modeling to only the risk for developing diabetes might have influenced the prediabetes A1C criterion. Although numerous studies have shown that glycemia is not an independent risk factor for CVD 14 — 21 , it certainly is for the development of diabetes.

Similarly, the risk with the A1C IEP criterion of 6. Claims have been made that treating people with prediabetes with antihyperglycemic drugs metformin, thiazolidinediones [TZD], α-glucosidase inhibitors, glucagon-like peptide 1 agonists, basal insulin has delayed or even prevented the development of diabetes.

This is a misinterpretation of the situation. These drugs have simply treated a level of glycemia lower than the diagnostic criteria for diabetes retarding its increase to the level at which a diagnosis of diabetes would occur. After these drugs were discontinued, the prevalence of diabetes in treated individuals mirrored that in the placebo group.

However, the time course of action of a drug is much more related to its tissue biologic effects than to the pharmacokinetics of its concentration in the blood.

It is well established that it takes 2—4 weeks for both metformin and sulfonylureas to exert their maximal effects when started 33 — Although the author could find no studies examining the time course of the effect of metformin wearing off, it takes 2—4 weeks for the effect of a sulfonylurea tolazamide to completely dissipate Troglitazone, a TZD that was removed from the market because of hepatic toxicity, was used for a mean of 0.

In those who had not developed diabetes during the intervention period, the rate of development of diabetes was the same in both groups during the 2- to 3-month washout period after both rosiglitazone and its placebo were discontinued 39 and 1. The Outcome Reduction With Initial Glargine Intervention ORIGIN study compared people with CVD risk factors who also had IFG, IGT, or early type 2 diabetes and who were given either glargine insulin or placebo The pathophysiologic abnormalities of insulin resistance and progressive β-cell dysfunction that characterize prediabetes were not fundamentally altered by these drug treatments 42 , 43 , which explains the lack of any long-term effects when these medications were discontinued Even so, should metformin treatment be offered to individuals whose glycemic parameters are near the diagnosis for diabetes, i.

There are three arguments against this. Second, approximately one-third of people with prediabetes return to normal glucose regulation NGR. After the study ended, the percent of participants who returned to NGR 1.

Third, as described previously, the diagnostic criteria for diabetes were selected because the risk for microvascular complications increased beyond that level of glycemia. Metformin, the preferred initial drug for treating patients with diabetes, is started to lower glycemia to levels that are not associated with this risk.

Five studies 51 — 55 have shown that the development or progression of retinopathy and microalbuminuria over a 6- to year period was almost nil if A1C levels were kept below 7. So, given that two-thirds of people with prediabetes do not develop diabetes over many years 45 — 47 , and in approximately one-third glycemia returns to normal 40 , 45 , 47 — 50 , why put people who are not at risk for the microvascular complications of diabetes when prediabetes is diagnosed on a drug possibly for the rest of their lives that has no immediate advantage except to lower subdiabetes glycemia to even lower levels?

This Perspective is not arguing against the benefit of delaying the development of diabetes. Rather, it is pointing out that the benefit of delay achieved with medication must be weighed against the potential adverse effects of the drug, its cost, and the important fact that a large number of people with the diagnosis of prediabetes will not develop diabetes and metformin would be of no benefit for them.

The argument is that lifestyle interventions, especially weight loss in overweight and obese individuals, should be pursued rather than use of a medication. It seems more prudent to identify individuals at the highest risk for developing diabetes—i. Meanwhile, these individuals should be intensely counseled on lifestyle interventions to reduce the risk of developing diabetes, and the risk factors for CVD should be aggressively addressed.

See accompanying article, p. Duality of Interest. No conflicts of interest relevant to this article were reported. Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.

filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 43, Issue 9.

Next Article. Article Information. Article Navigation. Perspectives in Care August 11 Metformin Should Not Be Used to Treat Prediabetes Mayer B.

Davidson Charles R. Drew University, Los Angeles, CA. Corresponding author: Mayer B. Davidson, mayerdavidson cdrewu.

This Site. Google Scholar. Diabetes Care ;43 9 — Article history Received:. Connected Content. A commentary has been published: Metformin Should Be Used to Treat Prediabetes in Selected Individuals. Get Permissions. toolbar search Search Dropdown Menu.

toolbar search search input Search input auto suggest. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Diabetes Prevention Program Research Group.

Long-term effects of metformin on diabetes prevention: identification of subgroups that benefited most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study.

Search ADS. More evidence for a prevention-related indication for metformin: let the arguments resume! Centers for Disease Control and Prevention. National Diabetes Statistics Report, Department of Health and Human Services.

Accessed 2 February National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Clinical irrelevance of the current diagnostic criteria for abnormal carbohydrate metabolism in asymptomatic individuals.

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Correction to the report on the diagnosis and classification of diabetes.

International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. American Diabetes Association. Identifying adults at high risk for diabetes and cardiovascular disease using hemoglobin A1c.

National Health and Nutrition Examination Survey — Risk of cardiovascular disease and death in individuals with prediabetes defined by different criteria: the Whitehall II Study.

Long-term absolute risk for cardiovascular disease stratified by fasting glucose level. Prediabetes and risk for cardiac death among patients with coronary artery disease: the ARTEMIS Study.

Prediabetes and risk for cardiovascular disease by hypertension status in black adults: the Jackson Heart Study. Glycated hemoglobin, prediabetes, and the links to cardiovascular disease: data from UK Biobank. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes.

A1C was reduced by 0. The mean time from randomization to diagnosis was 99 weeks SD 47 for the 26 in the liraglutide group vs. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over weeks among all randomized was 2.

The limitations included the fact that withdrawn individuals were not followed up after discontinuation, cost effectiveness of the active therapy compared to healthy behaviour interventions alone and questionable long-term adverse effects.

A systematic review and meta-analysis compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes Thirty-five trials 43, participants with variable risk of bias were included. Definitive conclusions may be limited in the context of the moderate degree of heterogeneity, variable risk of bias, and short-term follow-up duration of the available evidence to date.

Many limitations exist in this paper, including not all subjects being randomized and biases in publication Additionally, the cost-benefit analysis for bariatric surgery as a primary tool to prevent diabetes is unclear. Hence, more data is needed before recommending bariatric surgery routinely to prevent diabetes.

The reasons for this are multifactorial and include genetic susceptibility, altered fat distribution more visceral fat with greater insulin resistance and higher prevalence of metabolic syndrome.

Many of them develop diabetes at a younger age and often have complications at the time of diagnosis due to long-standing, pre-existing diabetes.

As a result, there may be a benefit of delaying the onset of diabetes in this population. The Indian Diabetes Prevention Programme randomized people with IGT diabetes in Chennai, India to 4 groups: healthy behaviour interventions; metformin; healthy behaviour interventions and metformin; and control with a median follow up of 30 months.

The relative risk reduction was Another study utilizing a stepwise approach of healthy behaviour interventions with the option of adding metformin reduced the risk of type 2 diabetes in Asian Indian adults This was a randomized, controlled trial of Asian Indian adults with overweight or obesity with isolated IGT, isolated IFG, or IFG and IGT in Chennai, India.

The primary outcome of diabetes incidence was assessed biannually and compared across study arms using an intention-to-treat analysis. During 3 years of follow up, Among subgroups, RRR was stronger in participants 50 years or older, male, or with obesity. Most participants Limitations included lack of power for subgroup comparisons, simplistic assessment of physical activity, and potential for lack of generalizability since the population was Asian Indian only.

The above approach of stepwise prevention intervention may lead to cost savings, fewer complications and lower morbidity, but it remains to be proven with hard clinical endpoints. Healthy behaviour interventions not only reduce the risk of diabetes but have other health benefits, so the overall benefit is positive with little harm.

One must keep in mind that the measures of prevention must be delivered in a culturally sensitive manner to these populations. At a macro-level, the type 2 diabetes epidemic has been attributed to urbanization and environmental transitions, including sedentary occupations, increased mechanization, improved transportation, as well as increased accessibility to unhealthy diets with high-calorie content and large portion sizes.

In recent decades, men and women around the globe and in Canada have gained weight, largely due to changes in dietary patterns and decreased physical activity levels. The dominant effect of obesity in precipitating glucose intolerance and its consequences suggests that reversal of the diabetes epidemic can only come about with urgent and substantial changes to health behaviours on a population level.

It is important to recognize that the health sector on its own cannot accomplish population-wide changes. New strategic relationships with groups that have an impact on health e. food industry and construction industry are needed to help create an environment more conducive to an active lifestyle and healthy eating habits.

Major legislative and other regulatory measures may be required similar to those needed to address illness arising from tobacco usage. Some examples of this are transformation of work environment, development of school curriculum to improve physical and nutritional education, improvement of food labelling on packaged foods, mandating nutrition labelling of restaurant foods and regulating advertisements, especially to children, etc.

In addition, food choices may be influenced by price increases taxation or price decreases subsidies.

Greater intake of sugar-sweetened beverages has been associated with higher type 2 diabetes risk in a meta-analysis 53 and a pooled analysis of European cohorts This association remains significant even after adjusting for BMI, suggesting that the deleterious effects of sugar-sweetened beverages on diabetes are not entirely mediated by body weight.

A1C , glycated hemoglobin; BMI , body mass index; CI , confidence interval; CV , cardiovascular; CVD , cardiovascular disease; EVOO, extra virgin olive oil; GDM , gestational diabetes; HR , hazard ratio; IFG , impaired fasting glucose; IGT , impaired glucose tolerance. Literature Review Flow Diagram for Chapter 5: Reducing the Risk of Developing Diabetes.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group P referred R eporting I tems for S ystematic Reviews and M eta- A nalyses: The PRISMA Statement. PLoS Med 6 6 : e pmed For more information, visit www. Prebtani reports support from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Sanofi and Janssen, outside the submitted work.

Bajaj reports personal fees from Abbott, and grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi, outside the submitted work. Goldenberg reports personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Servier, outside the submitted work.

Yvonne Mullan has nothing to disclose. All content on guidelines. ca, CPG Apps and in our online store remains exactly the same. For questions, contact communications diabetes. Become a Member Order Resources Home About Contact DONATE. Next Previous. Key Messages Recommendations Figures Full Text References.

Chapter Headings Introduction Reducing the Risk of Developing Type 1 Diabetes Reducing the Risk of Developing Type 2 Diabetes Healthy Behaviour Interventions Medical Nutrition Therapy Dietary Patterns Physical Activity Pharmacotherapy Bariatric Surgery Diabetes Prevention in High-Risk Ethnicities Population Level Interventions for Prevention of Type 2 Diabetes Author Disclosures.

Key Messages As safe and effective preventive therapies for type 1 diabetes have not yet been identified, any attempts to prevent type 1 diabetes should be undertaken only within the confines of formal research protocols. When initiated early, the effects of healthy behaviour interventions are long lasting more than 20 years.

A registered dietitian can educate you about dietary changes that may help reduce your risk for developing diabetes. Regular physical activity is also important to reduce your risk of diabetes. If healthy behaviour changes are not enough to normalize your blood glucose, your health-care provider may recommend that you use medication in addition to ongoing healthy behaviour changes to manage your prediabetes.

Introduction Ideal prevention strategies for both type 1 and type 2 diabetes should range from efforts focused on individuals identified as being at risk for developing diabetes to broader group- and population-based strategies. Reducing the Risk of Developing Type 1 Diabetes Type 1 diabetes is a chronic autoimmune condition characterized by destruction of pancreatic beta cells.

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 6.

Healthy Behaviour Interventions A majority of the randomized controlled trials with healthy behaviour interventions enrolled participants with IGT based on OGTT results.

Medical Nutrition Therapy Nutrition therapy and counselling are essential components of the treatment and management of prediabetes. Dietary Patterns There is strong evidence to support the use of the Mediterranean diet in diabetes prevention.

Diets Emphasizing Specific Foods Increased consumption of whole grains and dairy products have shown promising results with respect to decreased incidence of type 2 diabetes. Whole grains A large prospective cohort of postmenopausal women from the Women's Health Initiative Observational Study demonstrated that the consumption of whole grains was inversely associated with incident type 2 diabetes over a median 7.

Dairy A meta-analysis of 17 cohort studies 30 reported an inverse association between intakes of total dairy, low-fat dairy products and cheese and risk of type 2 diabetes Physical Activity Higher levels of leisure time physical activity LTPA are associated with substantially lower incidence of type 2 diabetes Pharmacotherapy Metformin Metformin was used in a second randomized arm of the DPP and compared to lifestyle and to placebo 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 3, individuals with obesity Liraglutide Liraglutide has been shown to prevent IGT conversion to type 2 diabetes and cause reversion to normoglycemia Vitamin D A systematic review and meta-analysis compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes Population Level Interventions for Prevention of Type 2 Diabetes At a macro-level, the type 2 diabetes epidemic has been attributed to urbanization and environmental transitions, including sedentary occupations, increased mechanization, improved transportation, as well as increased accessibility to unhealthy diets with high-calorie content and large portion sizes.

Recommendations In individuals with prediabetes, a structured program of healthy behaviour interventions that includes moderate weight loss and regular physical activity of a minimum of minutes per week over 5 days a week should be implemented to reduce the risk of type 2 diabetes [Grade A, Level 1A 16,17 for individuals with IGT; Grade B, Level 2 [23] for individuals with IFG; Grade D, Consensus for individuals with A1C 6.

In individuals at risk for type 2 diabetes, dietary patterns may be used to reduce the risk of diabetes, specifically: Mediterranean-style [Grade C, Level 3 26 ] DASH Dietary Approaches to Stop Hypertension [Grade C, Level 3 28 ] AHEI Alternate Healthy Eating Index [Grade C, Level 3 28 ].

In individuals with prediabetes, pharmacologic therapy with metformin may be used to reduce the risk of type 2 diabetes [Grade A, Level 1A 17,33 for individuals with IGT; Grade D, Consensus for individuals with IFG or A1C 6.

Abbreviations: A1C , glycated hemoglobin; BMI , body mass index; CI , confidence interval; CV , cardiovascular; CVD , cardiovascular disease; EVOO, extra virgin olive oil; GDM , gestational diabetes; HR , hazard ratio; IFG , impaired fasting glucose; IGT , impaired glucose tolerance.

Author Disclosures Dr. References Gale EA, Bingley PJ, Emmett CL, et al. European Nicotinamide Diabetes Intervention Trial ENDIT : A randomised controlled trial of intervention before the onset of type 1 diabetes.

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Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. Delahanty LM, Pan Q, Jablonski KA, et al. Effects of weight loss, weight cycling, and weight loss maintenance on diabetes incidence and change in cardiometabolic traits in the Diabetes Prevention Program. Maruthur NM, Ma Y, Delahanty LM, et al.

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Diabetologia ;— Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: A Japanese trial in IGT males. Diabetes Res Clin Pract ;— Saito T, Watanabe M, Nishida J, et al. Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: A randomized controlled trial.

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Benefits of the Mediterranean diet: Insights from the PREDIMED Study. Prog Cardiovasc Dis ;— Esposito K, Chiodini P, Maiorino MI, et al.