The Burden of Prediabetes

The Burden of Prediabetes

Prevalence

Prediabetes is a condition defined by the presence of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) that has not yet reached the thresholds for diagnosable type 2 diabetes mellitus (T2DM). Prediabetes raises short-term absolute risk of T2DM by 3- to 10-fold.1 Seventy-nine million people-35% of the US population-have prediabetes,1,2 and it is estimated that up to 70% of people with prediabetes may develop T2DM during their lifetimes.2,3

Worldwide, the number of people with IGT is estimated to be 280 million; by 2030, projections are that 398 million individuals will have IGT.4 According to the National Health and Nutrition Examination Survey (NHANES), in 2005-2006, 34.6% of US residents had prediabetes.5 Of these individuals, 19.4% had IFG only, 5.4% had IGT only, and 9.8% had both IFG and IGT. Of these individuals with prediabetes, only 4.8% reported receiving a formal diagnosis from their physicians. None received oral antihyperglycemic agents, while the percentage who received a physician recommendation for exercise or diet was 31.7% and 33.4%, respectively.5

In the 2006 National Health Interview Survey, the US Centers for Disease Control and Prevention (CDC) analyzed responses to questions regarding prediabetes for the first time. This was done to assess the prevalence of self-reported prediabetes among US adults, as well as the prevalence of respondents engaging in activities that can reduce diabetes risk.6 This report determined that, although at least one-fourth of US adults have prediabetes, only an estimated 4% of US adults have been told they have prediabetes.6 Furthermore, among those diagnosed with prediabetes, 68% had tried to lose or control their weight, 60% had reduced dietary fat or calories, 55% had increased their physical activity or exercise, and 42% had engaged in all 3 activities.6

Etiology

Prediabetes is a state of abnormal glucose homeostasis characterized by the presence of IFG, IGT, or both. This abnormal glucose homeostasis is a result of both beta-cell failure and insulin resistance.1,7-9 Prediabetes and subsequent T2DM likely develop as a result of polygenic defects that predispose affected individuals to the disease.7-9 Environmental factors such as a sedentary lifestyle and a high-fat diet can exacerbate defects in both insulin secretion from pancreatic beta-cells and insulin action in muscle and adipose tissues.

The modest hyperglycemia characteristic of the prediabetic state (A1C 5.5% to 6.4%) results in glucotoxicity, while in overweight individuals (particularly those with central adiposity), elevated free fatty acid (FFA) levels lead to lipotoxicity. Both gluco- and lipotoxicity worsen beta-cell secretion, which in turn aggravates hyperglycemia.7-10

Pathophysiology

IFG and IGT represent the transitional states of abnormal glucose regulation that occur between normal glucose homeostasis and T2DM.3 Both muscular and hepatic insulin resistance are present in individuals with IFG and/or IGT: individuals with isolated IFG have hepatic insulin resistance and normal muscle insulin sensitivity, while individuals with isolated IGT have normal to slightly decreased hepatic insulin sensitivity and moderate to severe muscle insulin resistance.3

Isolated IFG is associated with decreased first-phase (0-10 min) insulin secretory response to intravenous (IV) glucose, decreased early phase (first 30 min) insulin response to oral glucose, and normal late-phase (60-120 min) insulin response. Isolated IGT is associated with decreased early phase insulin response to oral glucose and results in a severe deficit in late-phase insulin secretion.3

A wide variety of organ systems are involved in T2DM pathophysiology, with many defects contributing in the progression from prediabetes to T2DM. The primary defects that lead to T2DM are impaired insulin secretion from beta-cells, impaired insulin action in muscle, and increased hepatic glucose production.11 (For more information, see the T2DM section.) The complex interplay between these defects contributes to the ongoing progression of T2DM.

The intermediate condition of prediabetes constitutes inherent disease risk for the progression to diabetes. The rate of progression to diabetes for patients with IGT is 6% to 10% per year. For persons with both IFG and IGT, the cumulative incidence of diabetes by 6 years may be as high as 65% (compared with levels of approximately 5% for individuals with normal glucose levels).1,12

Economic Burden

There is mounting evidence that prediabetes is associated with higher medical costs and increased risk for certain diabetic comorbidities. For example, even somewhat elevated blood glucose levels are associated with an increased risk of coronary heart disease (CHD), hypertension, retinopathy, and mortality.13

The high prevalence of prediabetes suggests substantial implications for the health system with even a slight increase in per capita healthcare use and disease risk. A study conducted in 2009 by Zhang and colleagues used medical claims data to estimate per capita excess healthcare use associated with prediabetes, and combined these data with national estimates of healthcare use and medical costs to calculate national expenditures related to prediabetes.13

This study found that patients with confirmed prediabetes had approximately 34% more ambulatory visits per year compared to the general population—ranging from 9% more visits for cardiovascular disease (CVD) and peripheral vascular disease to 92% more visits for hypertension. In addition, using patient demographics to extrapolate to the national level, the national cost of prediabetes was estimated to exceed $25 billion (equivalent to approximately $443 per adult with prediabetes).13

Children and Adolescents

Prediabetes is uncommon in children and adolescents, especially those younger than 10 years of age. However, incidence has increased in recent years.1 According to NHANES data, during 1999-2000, the prevalence of IFG among US adolescents aged 12 to 19 years was 7%. However, in 2005-2006, NHANES data were examined to estimate the incidence of IFG, IGT, and prediabetes among the adolescent population and to assess selected correlates of these dysglycemic states.14 This study found an unadjusted prevalence of IFG, IGT, and prediabetes of 13.1%, 3.4%, and 16.1%, respectively. These data suggest that there was a 47% increase in IFG in US adolescents over this 5- to 6-year period. Additional 2005-2006 NHANES study findings included:

  • A 2.4-fold higher prevalence of prediabetes in boys than girls (95% CI 1.3-4.3)14
  • A lower rate of prediabetes in non-Hispanic blacks compared with non-Hispanic whites (prevalence ratio [PR] 0.6, 95% CI 0.4-0.9)14
  • A lower rate in adolescents aged 16 to 19 years vs those aged 12 to 15 years (PR 0.6, CI 0.4-0.9)14
  • A 2.6-fold higher rate in overweight adolescents compared with those at normal weight (95% CI 1.3-5.1)14
  • A 2.7-fold higher prediabetes rate in adolescents with ≥2 cardiometabolic risk factors compared to those with none (95% CI 1.5-4.8)14
  • A 4-fold higher prevalence in adolescents with hyperinsulinemia (95% CI 2.2-7.4) than those without13

To learn more, please see sections on prediabetes screening, diagnosis, monitoring, comorbidities and complications, and treatment.

References

  1. Garber AJ, Handelsman Y, Einhorn D, et al. Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin? A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists. Endocr Pract. 2008;14(7):933-946.
  2. Centers for Disease Control and Prevention. 2011 National Diabetes Fact Sheet: Diagnosed and undiagnosed diabetes in the United States, all ages, 2010. 2011; Available at: http://www.cdc.gov/diabetes/pubs/estimates11.htm#10.
  3. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007;30(3):753-759.
  4. International Diabetes Federation. The Global Burden. 2012; Available at: http://www.idf.org/diabetesatlas/5e/the-global-burden.
  5. Karve A, Hayward RA. Prevalence, diagnosis, and treatment of impaired fasting glucose and impaired glucose tolerance in nondiabetic U.S. adults. Diabetes Care. 2010;33(11):2355-2359.
  6. Centers for Disease Control and Prevention. Self-reported prediabetes and risk-reduction activities–United States, 2006. Weekly. 2008;57(44):1203-1205.
  7. Kahn SE. The importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001;86(9):4047-4058.
  8. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46(1):3-19.
  9. Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2008;29(3):351-366.
  10. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(Suppl 2):1-53.
  11. DeFronzo RA, Banerji M, Bray GA, et al. Actos Now for the prevention of diabetes (ACT NOW) study. BMC Endocr Disord. 2009;9:17.
  12. de Vegt F, Dekker JM, Jager A, et al. Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study. JAMA. 2001;285(16):2109-2113.
  13. Zhang Y, Dall TM, Chen Y, et al. Medical cost associated with prediabetes. Popul Health Manag. 2009;12(3):157-163.
  14. Li C, Ford ES, Zhao G, Mokdad AH. Prevalence of pre-diabetes and its association with clustering of cardiometabolic risk factors and hyperinsulinemia among U.S. adolescents: National Health and Nutrition Examination Survey 2005-2006. Diabetes Care. 2009;32(2):342-347.