Screening and Diagnosis of Type 2 Diabetes

In 2002, nearly 18.2 million people in the US were believed to have diabetes (~6.3% of the population). Of this population, ~13 million were diagnosed and 5.2 million undiagnosed. Type 2 diabetes accounts for 90 % to 95% of all diagnosed cases of diabetes. In 2002, the total cost (direct + indirect) of diabetes in the US was nearly $132 billion.[1] Evidence suggests that between one third and one half of all cases of diabetes are undiagnosed and patients may have preclinical disease for as long as 12 years prior to diagnosis. At diagnosis, 50% of patients have some form of microvascular complications (nephropathy, retinopathy, neuropathy) and have a 2- to 4-fold increase in risk of developing cardiovascular disease.[1,2] Screening for Type 2 diabetes would allow early recognition of preclinical diabetes with the potential to initiate early treatment with the hopes of delaying long-term complications.[2]

Screening of type 2 diabetes

Screening techniques are utilized to identify asymptomatic individuals at high risk from that of an individual at low risk for developing diabetes (Table 1). A variety of screening assessment tools are available including risk assessment questionnaires, portable capillary blood assessments, and laboratory-based assessments. Each of these techniques utilizes various thresholds and cutoff points in the determination of risk assessment. In general, screening tests are not part of diagnostic tests. Screenings should be rapid, simple, and safe. A positive screening test only indicates an individual is more likely to develop diabetes compared with an individual with a negative screening test. After a positive screening result has been obtained, the clinician then should perform standardized diagnostic tests to establish a definitive diagnosis.[1] Table 2 illustrates the appropriate criteria for initiating screenings in asymptomatic individuals; each of these criteria will be discussed in the following sections.

Table 1. Factors associated with increased risk of diabetes[1,2]

Table 2. Criteria for asymptomatic screenings[2,5]

The public health burden of type 2 diabetes

According to 2002 prevalence data,[1] 6.3% of the population has diabetes and this number is estimated to increase to 8.9% by the year 2025.[1] Diabetes accounts for 60% of all nontraumatic amputations, 15% of all cases of blindness, and 43% of new cases of end-stage renal disease (ESRD).[1,2] Diabetes also contributes substantially to cardiovascular disease, stroke, peripheral vascular disease, disability, congenital malformations, and perinatal death.[2] Costs related to diabetes in the US during 2002 were estimated at $132 billion in medical expenditures and lost productivity.[2] Diabetes is a significant health problem and early screening has the potential to decrease the overall burden of disease.

Natural history

Diabetes progresses through several stages beginning with biological onset followed by a period in which the disease is clinically unidentifiable. As hyperglycemia continues to increase, screening tests become more sensitive and can detect the presence of the disease. Diabetes-related complications, if not already present at diagnosis, may develop in response to hyperglycemia and duration of disease resulting in major disability and, ultimately, death. Figure 1 outlines the clinical stages associated with screening for diabetes. Major risk factors associated with diabetic microvascular complications are listed in Table 3.

Table 3. Risk factors associated with diabetic microvascular complications[5]

*New studies indicate dyslipidemia contributes to diabetic retinopathy and nephropathy.[1,2]

Table taken from reference 4.

Diabetes has a recognizable preclinical (asymptomatic) stage

Diabetes has a long preclinical phase that has been estimated to be approximately 10 to 12 years.[1,2]Assuming a linear increase in prevalence of retinopathy over time, the interval between prevalence of no retinopathy and clinical diagnosis is estimated to be 4 to 7 years. Assuming that the time between onset of diabetes and the appearance of retinopathy is 5 years, the time between onset of diabetes and clinical diagnosis may be as long as 12 years.[10] Therefore, during this 12-year interval, diabetes could potentially be recognized through screening.

Benefits of early treatment

The United Kingdom Prospective Diabetes Study has established that intensive blood glucose control can significantly reduce the long-term complications of diabetic microvascular complications by 25%.[1] As previously discussed, individuals with diabetes have a high risk of developing macrovascular complications. Early detection of diabetes allows for more time to initiate early and aggressive treatment options to reduce macrovascular risk with potential long-term benefits. However, to date there is no evidence suggesting that screening and early disease recognition actually leads to early initiation of currently available treatment options.[2]

Reliable tests can detect preclinical disease

Ideally, a screening test should be both sensitive (high probability of being positive when subject has diabetes) and specific (high probability of being negative when subject does not have diabetes). Screening test results should also be reliable and reproducible, meaning consistent results are obtained when test is performed more than once. Table 4 identifies the advantages and disadvantages of current screening methods.

Table 4. Advantages and disadvantages of current screening methods[2,7]

*Fasting plasma glucose the preferred screening and diagnostic test by American Diabetes Association[5]

Diabetes screening is cost effective

Treatment of hyperglycemia in patients diagnosed with diabetes is cost effective, with a cost estimated at $16,000 per quality-adjusted life year (QALY).[1] Whether screening for and treating patients with screen-identified diabetes is cost effective is largely unknown. However, one study estimated the lifetime benefits of a one-time opportunistic screening with diagnosis for type 2 diabetes as cost effective when it occurs in general practice. "The identified cost per case of diabetes was $1200. Diabetes was diagnosed on average 5.5 years earlier with an estimated average cost of treating a newly diagnosed patient of $1007. The lifetime cost of diabetes was $3400 higher with screening. Overall, the cost per life-year gained was $236,400 and the cost per QALY gained was $56,000.[1] The estimate is lower than breast cancer screening with annual mammography (women aged 50-65), but higher than cervical screening with 4 yearly smears (women aged 20-75)."[1]

Diabetes screening currently not an ongoing process

Unfortunately, screenings inevitably miss some individuals with diabetes (sensitivity <100%) due to individuals not presenting themselves for screening, and incident cases replenishing the pool of undiagnosed individuals. To fully address the problem of undiagnosed diabetes, screening programs must be ongoing. For ongoing screening to occur, there must be a commitment to develop and sustain screening activities. Several health agencies, task forces, and professional organizations have published recommendations for screening of type 2 diabetes. These recommendations are listed in Table 5.

Table 5. Current screening recommendations for type 2 diabetes[7]

AAFP = American Academy of Family Physicians; ACP = American College of Physicians; BDA = British Diabetic Association; CTFPHE = Canadian Task Force on the Periodic Health Examination; NS = not stated.

Diagnosis of type 2 diabetes

There are 3 assays used to diagnose diabetes: 75 g oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), and hemoglobin A1C (A1C). Each assay used to diagnose diabetes must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present. Although the OGTT is more sensitive and modestly more specific than FPG at diagnosing diabetes, OGTT is poorly reproducible and rarely performed in practice. Since FPG is easy to use, is accepted by patients, and has a lower cost, FPG is considered the preferred screening and diagnostic test by the American Diabetes Association (ADA). Current criteria for the diagnosis of diabetes in nonpregnant adults is shown in Table 6 and for adolescents in Table 7.

Table 6. ADA criteria for the diagnosis of diabetes in nonpregnant adults[5]

Table 7. ADA criteria for testing for type 2 diabetes in adolescents[5]

References

1. American Diabetes Association. Diabetes Statistics. Available at: http://www.diabetes.org/diabetes-statistics.jsp. Accessed June 2006.
2. Lawrence J, Robinson A. Screening for diabetes in general practice. Prev Cardiol. 2003;6:78-84.
3. American Diabetes Association. Dyslipidemia management in adults with diabetes. Diabetes Care. 2004;25(suppl 1):S68-S71.
4. Engelgau MM, Aubert RE, Thompson TJ, Herman WH. Screening for NIDDM in nonpregnant adults: a review of principles, screening tests, and recommendations. Diabetes Care. 1995;18:1606-1618.
5. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2004;27(suppl 1):S15-S35.
6. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025. Diabetes Care. 1998;21:1414-1431.
7. Engelgau MM, Venkat Narayan KM, Herman WH. Screening for type 2 diabetes. Diabetes Care. 2000;23:1563-1580.
8. American Diabetes Association. Economic costs of diabetes in the U.S. in 2002. Diabetes Care. 2003;26:917-931.
9. American Diabetes Association. Diabetic Retinopathy. Diabetes Care. 1998;21(suppl 1):S47-S49.
10. Mulec H, Johnsen SA, Wiklumd O, Bjorck S. Cholesterol: a renal risk factor in diabetic nephropathy? Am J Kidney Dis. 1993;22:196-201.
11. Harris MI, Klein R, Welborn TA, et al. Risk factors for non-insulin dependent diabetes mellitus occurs at 4-7 years before clinical diagnosis. Diabetes Care. 1992;15:815-819.
12. Diabetes United Kingdom. Audit shows 10-year delay in diagnosing type 2 diabetes. Diabetes Update. 2000;Winter:1.
13. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-853.
14. Herman WH, Dasbach EJ, Songer TJ, et al. The cost-effectiveness of intensive therapy for diabetes mellitus. Endocrin Metab Clin North Am. 1997;26:679-695.
15. CDC Diabetes Cost-Effectiveness Study Group. The cost effectiveness of screening for type 2 diabetes. JAMA. 1998;280:1757-1763.
16. Graham JD, Corso PS, Morris JM, et al. Evaluating the cost-effectiveness of clinical and public health measures. Annu Rev Public Health. 1998;19:125-152.