Diabetes Care

Volume 23 Supplement 2
Data, Results, and Consequences of Major Trials With Focus on Type 2 Diabetes
Proceedings from a Symposium


ORIGINAL ARTICLE


Type 2 Diabetes Worldwide According to the New Classification and Criteria


Jonathan E. Shaw, MRCP
Paul Z. Zimmet, MD, PHD, FRACP
Daniel McCarty, PHD
Maximilian de Courten, MD


Two major reports have recently revised the classification of and diagnostic criteria for diabetes. Classification was previously based on the need for insulin (insulin-dependent or non–insulin-dependent), but this has become increasingly confusing. Now, the type of diabetes is determined by the etiological process rather than the treatment modality. Type 1 diabetes is thus characterized by islet cell destruction and type 2 diabetes by a combination of defects in insulin secretion and action. An individual with either type of diabetes may be on any treatment modality. This classification should prove to be more logical and, for example, allow latent autoimmune diabetes in adults, which typically does not require insulin at presentation, to be classified as type 1 diabetes. The fasting plasma glucose diagnostic threshold for diabetes has been lowered to 7.0 mmol/l (126 mg/dl), and impaired fasting glucose (fasting plasma glucose 6.1–6.9 mmol/l [110–125 mg/dl]) has been introduced as a new category of intermediate glucose metabolism. These changes recognize that the old fasting threshold did not match the 2-h (postload) threshold well and that both micro- and macrovascular disease develop at lower fasting glucose levels than previously recognized. Although the prevalences of diabetes according to the new fasting and 2-h criteria are now similar in most populations, the actual individuals identified as having diabetes are often different. Over 30% of all those with diabetes have a nondiabetic fasting glucose but still have increased cardiovascular mortality. Thus, it is important to retain the oral glucose tolerance test for the diagnosis of diabetes.

Diabetes Care 23 (Suppl. 2):B5–B10, 2000


Type 2 diabetes affects large numbers of people from a wide range of ethnic groups and at all social and economic levels throughout the world. Currently, at least 120 million people suffer from type 2 diabetes, but by the year 2010, 220 million people are projected to have the disease (1). Diabetes is among the five leading causes of death in most countries (2), yet mortality statistics greatly underestimate the true rate of diabetes-related mortality because diabetes is frequently underreported on death certificates (2,3). Therefore, diabetes is often ignored when public health priorities are set, and quite apart from the health impact, the economic cost of diabetes and its complications is enormous for health care, and loss of productivity to society is great (2).

The extraordinary high prevalence of type 2 diabetes reported over 20 years ago in the Pima Indians (4) and the Micronesian Nauruans in the Pacific (5) and then later in other Pacific and Asian island populations (68) suggested the potential for a future diabetes epidemic. This scenario proved to be correct, and type 2 diabetes has now reached epidemic proportions in many developing nations (9) as well as in disadvantaged minorities in the developed countries. Examples of the latter include Australian Aboriginals and Torres Strait Islanders (10); Native, African-, and Mexican Americans (11); migrant Asian Indians (8); and some groups in the Middle East Arab states (12).

There is every reason to expect that over the next decade, the epidemic of type 2 diabetes will continue to escalate (1). Inevitably, diabetes and its complications will emerge as one of the major threats to future public health resources throughout the world at a huge economic and social cost, particularly in developing countries (13).

Against this global epidemic, changes proposed for the classification and diagnostic criteria for diabetes become very important not only for individual epidemiological studies, but also for global comparisons of incidence and prevalence. Therefore, the recommendations of the 1997 American Diabetes Association (ADA) report on classification and diagnostic criteria (14), followed by the 1998 provisional World Health Organization (WHO) recommendations (15), will have important implications. The outcomes of the changes should be better management of diabetes, due both to earlier diagnosis and better classification of cases for more appropriate therapy.

CHANGES IN CLASSIFICATION — In 1979 and 1980, both the U.S. National Diabetes Data Group (16) and WHO (17) tackled the task of classification and criteria of diabetes. The terms "juvenile-onset diabetes" and "maturity-onset diabetes" were replaced by insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes and non-insulin-dependent diabetes mellitus (NIDDM) or type 2 diabetes. The category impaired glucose tolerance (IGT) was also created. This classification was based on the patient's need (or lack thereof) of insulin for survival and potential etiologic mechanisms. Because heterogeneity exists in both type 1 and type 2 diabetes, the general applicability of the WHO classification has had limitations. The advantage of the latest ADA/WHO classification (Fig. 1), which results from new knowledge of the causes, is that it combines both clinical stages of hyperglycemia and the etiological types. The actual staging reflects that any etiological type can pass or progress through several clinical phases (both normoglycemic and hyperglycemic) during its natural history. Moreover, individuals may move in either direction, from stage to stage. The type of diabetes, however, is now determined by the etiological process rather than the treatment modality.

010631a.gif (77142 bytes)
Figure 1Classification of diabetes. ArrowRightbroken.gif (1099 bytes), In rare instances, patients in these categories may require insulin for survival.

The etiological types represent processes that may result in diabetes (e.g., -cell destruction results in type 1 diabetes) where insulin is required for survival to prevent the development of ketoacidosis. Type 2 diabetes results from insulin resistance and/or abnormal insulin secretion, either of which may predominate. In many instances, the specific molecular or metabolic causes are not yet known. However, as with diabetes resulting from specific gene mutations, e.g., glucokinase or mitochondrial DNA, when eventually determined, they will be reclassified under "other specific types," such as genetic, endocrine, drug-induced, etc. (15).

The new classification proposes that hyperglycemia, regardless of the underlying cause, can be subcategorized as follows:

  • Insulin-requiring for survival,
  • Insulin-requiring for control (i.e., for metabolic control, not for survival),
  • Non–insulin-requiring (i.e., with treatment by nonpharmacological methods or drugs other than insulin).

The designation of diabetes type is no longer dependent on which of these categories an individual is in, although the majority of people with type 1 diabetes require insulin for survival, and the majority of those with type 2 diabetes fall into the other two categories. This classification will hopefully remove the confusion between insulin-dependent and insulin-treated.

IGT and fasting hyperglycemia
IGT was previously a separate class but is now categorized as a stage in the natural history of disordered carbohydrate metabolism. IGT is coupled with impaired fasting glucose (IFG) (6.1–7.0 mmol/l [110–126 mg/dl]).

Latent autoimmune diabetes in adults
The form of diabetes described by our group (18), latent autoimmune diabetes in adults (LADA), is included within type 1 diabetes (autoimmune). Its slow onset distinguishes it from the more acute and dramatic onset of type 1 diabetes in children and adolescents. This form of diabetes has caused confusion in defining diabetes in adults in both clinical and research settings. A convincing argument for the importance of LADA comes from the U.K. Prospective Diabetes Study (UKPDS). Islet cell antibodies (ICA) and anti-GAD antibodies were measured at diagnosis in 3,672 patients selected by family physicians as having "typical" type 2 diabetes (19). Of these patients, the overall proportion with ICA was 6% and anti-GAD 10%. A total of 12% had either ICA or anti-GAD, and 4% had both. These subjects are clearly cases of type 1 diabetes or LADA, as judged by both phenotypic and genotypic features. The presence of autoantibodies correlated with a younger age and phenotypic features consistent with type 1 diabetes, such as early age at diagnosis, lower BMI, and reduced -cell function. At all ages, the presence of autoantibodies conferred an increased likelihood of decompensation to insulin therapy (19). Thus, 94% of patients aged <35 years positive for ICA and 84% of those positive for anti-GAD at baseline required insulin therapy within 6 years of diagnosis, compared with 14% of seronegative cases. Clearly, these data will be very important and need to be taken into account when defining the prevalence of type 1 and type 2 diabetes in adults.

CHANGES IN DIAGNOSTIC CRITERIA — The diagnostic criteria for diabetes have changed on a number of occasions over recent decades. In 1985, the WHO published diagnostic thresholds based on the 75-g oral glucose tolerance test (OGTT), which became the gold standard over subsequent years (20). These diagnostic cut points were based on the threshold for development of retinopathy, the glucose values that divide a bimodal distribution of glucose, and the glucose levels at which insulin levels start to decline. However, it has always been recognized that the glucose values that are chosen as diagnostic cut points are to a certain extent arbitrary because the distribution of blood glucose is continuous. Epidemiological data collected over the last decade recently led both the WHO and the ADA to review the diagnostic criteria (14,15). The new information related to the fasting plasma glucose (FPG) threshold (previously 7.8 mmol/l [140 mg/dl]) rather than to the 2-h plasma glucose (PG) threshold and indicated the following:

  • The threshold of FPG for developing diabetic retinopathy is <7.8 mmol/l (140 mg/dl) (14,21,22).
  • The majority of people with a 2-h PG above the diagnostic threshold of 11.1 mmol/l (200 mg/dl) have an FPG <7.8 mmol/l (140 mg/dl), whereas almost all of those with an FPG >7.8 mmol/l (140 mg/dl) also have a 2-h PG >11.1 mmol/l (200 mg/dl) (23,24). Thus, an FPG of 7.8 mmol/l (140 mg/dl) represents a more severe degree of hyperglycemia than a 2-h PG of 11.1 mmol/l (200 mg/dl).
  • Levels of FPG clearly below the threshold for diabetes are associated with an excess risk of cardiovascular disease, suggesting that an intermediate stage of glucose metabolism can be defined for FPG in a similar way to that in which IGT is defined for the 2-h PG (8,9).

As a result of these findings, the ADA and WHO (in 1997 and 1998, respectively) recommended the following changes to the diagnostic criteria (25,26):

  • The FPG threshold is lowered from 7.8 to 7.0 mmol/l (140 to 126 mg/dl).
  • IFG (FPG 6.1–6.9 mmol/l [110–125 mg/dl]) is introduced as a new category of intermediate glucose metabolism (named impaired fasting glycemia by the WHO).

These changes update the criteria to match the relevant data, although some data from Asian populations have suggested that the FPG equivalent to a post–glucose loading PG of 11.1 mmol/l (200 mg/dl) may be even lower than 6.0 mmol/l (108 mg/dl) (27). Consequent on these amendments to the fasting criteria, the ADA (but not the WHO) indicated that FPG rather than the OGTT should be the diagnostic test of choice both for clinical and epidemiological purposes. The fasting glucose has the advantage that it is considerably more reproducible than the 2-h PG and is simpler to perform than the OGTT.

shawt1.jpg (49593 bytes)

The requirement to confirm an abnormal test on a different day in an asymptomatic individual is retained by both the ADA and WHO. The impact of the changes is complex. They affect both diabetes and the intermediate states of carbohydrate metabolism: IGT and IFG.

Diabetes
What difference will these changes make to the prevalence of diabetes and to the individuals identified as having diabetes? Because the ADA has now recommended using only the new fasting criterion, whereas the 1985 WHO guidelines were heavily dependent on the 2-h value, it is this change from the OGTT to FPG alone that requires analysis. A number of studies have now been published comparing the old and new criteria (2837). These studies are summarized in Table 1 and reveal that the changes may have a rather variable impact. Compared with the old OGTT-based criteria and excluding people already known to have diabetes, the new fasting criterion identifies between 65% fewer (Mexico) and 42% more (Newcastle, U.K.) people as having newly diagnosed diabetes, depending on the population studied. Because in most populations a significant proportion (at least 50% in developed nations, but lower in developing nations) of all those with diabetes are already known to have the disease, the impact of these changes on the total prevalence will be somewhat less than these figures indicate, though how much less is unknown.

Furthermore, even when the total prevalence is similar by the two methods, the actual people identified by screening may be different. The percentage of individuals classified as having diabetes by the new FPG cutoff who also have diabetes according to the old criteria varies from only 41% (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe [DECODE]) to 91% (Japanese-Brazilians and residents of Hong Kong). It is not clear what drives this variation in the degree of classification disagreement, but in the DECODE Study of 16 different European populations (29), obese diabetic individuals were more likely to satisfy the fasting criterion, and nonobese diabetic individuals were more likely to satisfy the 2-h criterion. It is possible that ethnicity is also important, but there are not yet enough data to assess this. This change in the individuals who are identified raises the further question of whether changing to the new fasting threshold will alter the phenotype of diabetes or the associations between risk factors (such as obesity) and the subsequent development of diabetes. These issues are currently unresolved, although the Third National Health and Nutrition Examination Survey (NHANES III) shows that the mean HbA1c is higher in the group diagnosed by the new fasting criterion than in the group diagnosed by the 1985 WHO OGTT criteria (31).

The association of hyperglycemia and cardiovascular disease is a crucial one on which to test the validity of the new criteria. The Hoorn Study has shown that people with an FPG >7.0 mmol/l (126 mg/dl) (i.e., diabetic) but a nondiabetic 2-h PG have an abnormal cardiovascular risk profile (28), and data from two large cohorts of men with a nondiabetic 2-h glucose value at baseline showed an increased 20-year mortality when the baseline FPG was >7.0 mmol/l (126 mg/dl) (38). Similarly, evidence would now indicate that people whose only abnormality is in the postload state have elevated blood pressure and lipids (28) and have a higher cardiovascular mortality than their nondiabetic counterparts (39). Thus, isolated abnormalities in either the fasting or the postload state have important associations with cardiovascular disease, and while lowering of the fasting threshold will help to identify one group, abandonment of the OGTT may prevent or delay diagnosis in the other group. Cardiovascular risk, however, demonstrates again the arbitrary nature of glucose cut points. Blood glucose represents a continuous cardiovascular risk factor extending well into the normal range (40) and interacts with other risk factors.

Will the new criteria influence the total number of people in whom diabetes is actually diagnosed (rather than the prevalences estimated by epidemiological studies), and will an increased detection rate reduce morbidity and mortality? The simple lowering of the fasting threshold alone should increase the number of people who are classified as having diabetes. However, when lowering of the threshold is combined with a switch from using the OGTT to just using the FPG, it can be seen from Table 1 that the overall effect can be either to increase or decrease the prevalence as determined by epidemiological studies.

In routine clinical practice, the OGTT is rarely used, and in this setting, the number of people diagnosed should increase as a result of lowering the fasting threshold. However, the degree to which it will increase is unclear and probably depends more on increasing the number of people screened (by whichever diagnostic test) than it does on altering the parameters of the screening test. It is worth noting in this context that the proportion of diabetes that is undiagnosed is directly influenced by the diagnostic test and the thresholds used. NHANES III data show that when using the 1985 WHO criteria, this proportion was 44%, but was only 35% when using the new fasting criterion (41). Thus, future diagnostic rates will need to be analyzed and interpreted with caution.

Diagnosing type 2 diabetes earlier in its natural history can only be beneficial if therapy reduces mortality and morbidity. No study has specifically addressed this question of the long-term benefit of screening, but in a computer-simulated model, opportunistic screening for diabetes was shown to be cost-effective (42). Furthermore, the UKPDS has recently shown that intensive glucose-lowering therapy reduces the risk of microvascular disease (43) and that in obese diabetic patients, metformin reduces mortality and myocardial infarction (44).

IFG and IGT
Table 2 shows studies that compare the prevalence of IFG and IGT (28,3134,36,37,45,48). In seven of nine studies, IGT was more common than IFG. On average, there was 61% more people with IGT than with IFG. Similar to diabetes diagnosis, there was only limited agreement in the classification of individuals between the two systems. Only 22–46% (mean 37) of people with IFG also had IGT, and 19–37% (mean 24) of those with IGT were classified as having IFG.

shawt2.jpg (38396 bytes)

In a further twist to the complexity of changing the diagnostic criteria, the introduction of IFG requires that the prediction of subsequent diabetes among people with either IFG or IGT be reassessed. One of the original reasons for introducing IGT was that as well as increasing the risk of cardiovascular disease, it carried a high risk of progressing to diabetes, and this has been confirmed in a number of different studies (46). Therefore, IGT serves as an important risk factor for an individual. In addition, its prevalence can be used to suggest future changes in the prevalence of diabetes within a population (47), and it is being used to identify subjects suitable for diabetes prevention trials. Can IFG perform a similar role?

We have recently reported data from a prospective population-based study in Mauritius (48) addressing this issue. From a baseline population of 3,229 subjects, 609 had IGT and 267 had IFG, with only 118 of these subjects having both IFG and IGT. After 5 years of follow-up, 297 subjects had progressed to diabetes, of whom 148 had IGT at baseline, but only 77 had IFG at baseline (Fig. 2). Therefore, the ability of IFG to identify those who would progress to diabetes (sensitivity) was considerably less than that of IGT. However, for those people with IFG, the risk of progression (positive predictive value) was slightly higher for IFG than for IGT (29 vs. 24%). This difference between IFG and IGT should not be seen as necessarily indicating an absolute difference between the predictive properties of FPG and 2-h PG, but merely between the two categories as currently defined. Further work in other populations will be needed to assess the prognostic implications of IFG and to determine what advantage, if any, can be gained from changing the diagnostic limits of IFG.

010632a.gif (6586 bytes)
Figure 2Progression to diabetes over 5 years in Mauritius according to baseline glucose tolerance status (48).

Glycated hemoglobin
Changes in diagnostic criteria (14,15) have only addressed the use of blood glucose. Glycated hemoglobin, however, offers a number of potential advantages for diagnosis. It does not require the subject to be fasted or to wait 2 h for an OGTT, and its relationship with retinopathy is just as strong as those for fasting or 2-h glucose (14). Because glycated hemoglobin reflects both fasting and postprandial glucose, it may have advantages over either one. Furthermore, given its current role in the management of diabetes, its use in diagnosis would provide a valuable link between diagnostic thresholds and treatment targets. However, the difficulties that have been described above in trying to identify equivalent values of fasting and 2-h blood glucose are likely to be repeated for HbA1c, which inevitably will classify some individuals in a different way to that in which they are classified by blood glucose. These issues would need addressing, and detailed studies relating HbA1c to hard outcomes (including cardiovascular disease) would be needed to assess its value as a diagnostic tool. Other practical problems exist. Assays for HbA1c are not yet all standardized, and it is therefore not currently possible to produce diagnostic values that could be used universally. Access to HbA1c assays is limited in many parts of the developing world, and if HbA1c was adopted instead of blood glucose, diagnosis could become difficult.

SUMMARY — An improved understanding of the pathophysiology of diabetes has now allowed its classification to be based on etiological processes, not the form of therapy. Although a precise classification may not always be possible in clinical settings, the new system should lead to less confusing and more logical terminology.

Lowering the FPG threshold for diagnosing diabetes recognizes recent advances in the understanding of glycemic thresholds with respect to the risk of complications. It also makes the diagnosis of type 2 diabetes easier by putting less emphasis on the OGTT. However, this change (especially if the OGTT is abandoned) will have unpredictable effects on measurements of diabetes prevalence, will identify different individuals, and will make it difficult to compare old studies with new ones. In addition, IFG requires further study before its significance is fully understood. More prospective data from a variety of populations looking at both microvascular and macrovascular outcomes in relation to fasting and postload glucose values are still needed to clarify the diagnostic thresholds.


Acknowledgments — This work was partially supported by U.S. National Institutes of Health Grant DK-25446. J.E.S. is supported by a grant from the Institute for Diabetes Discovery, Branford, Connecticut.


References

1. Amos AF, McCarty DJ, Zimmet P: The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 14 (Suppl. 5):S7–S85, 1997

2. Finch CF, Zimmet PZ: Mortality from diabetes. In The Diabetes Annual/4. Alberti KGMM, Krall LP, Eds. Amsterdam, Elsevier, 1988, p. 1–16

3. Songer TJ, Zimmet PZ: Epidemiology of type II diabetes: an international perspective. Pharmacoeconomics 8 (Suppl. 1):1–11, 1995

4. Knowler W, Bennett P, Hamman R, Miller M: Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota. Am J Epidemiol 108:497–504, 1978

5. Dowse G, Zimmet P, Finch C, Collins V: Decline in incidence of epidemic glucose intolerance in Nauruans: implications for the thrifty genotype. Am J Epidemiol 133:1093–1104, 1991

6. Dowse G, Spark R, Mavo B, Hodge AM, Erasmus RT, Gwalimu M, Knight LT, Koki G, Zimmet PZ: Extraordinary prevalence of non-insulin-dependent diabetes mellitus and bimodal plasma glucose distribution in the Wanigela people of Papua New Guinea. Med J Aust 160:767–774, 1994

7. Zimmet P, Taylor R, Ram P, King H, Sloman G, Raper LR, Hunt D: The prevalence of diabetes and impaired glucose tolerance in the biracial (Melanesian and Indian) population of Fiji: a rural-urban comparison. Am J Epidemiol 118:673–688, 1983

8. Dowse G, Gareeboo H, Zimmet P, Alberti KGMM, Tuomilehto J, Fareed D, Brissonnette LG, Finch CF: High prevalence of NIDDM and impaired glucose tolerance in Indian, Creole and Chinese Mauritians. Diabetes 39:390–396, 1990

9. Zimmet P: Kelly West Lecture 1991: Challenges in diabetes epidemiology: from West to the Rest. Diabetes Care 15:232–252, 1992

10. Zimmet P, Dowse GK, Finch CF, Serjeantson S, King H: The epidemiology and natural history of NIDDM: lessons from the South Pacific. Diabetes Metab Rev 6:91–124, 1990

11. Bennett PH, Bogardus C, Zimmet P, Tuomilehto J: The epidemiology of non-insulin dependent diabetes: non-obese and obese. In International Textbook of Diabetes Mellitus. Alberti KGMM, DeFronzo R, Keen H, Zimmet P, Eds. London, Wiley, 1992, p. 147–176

12. King H, Rewers M, Zimmet P, Dowse G: WHO Adhoc Reporting Group: global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. Diabetes Care 16:157–177, 1993

13. Zimmet P, Lefebvre P: The global NIDDM epidemic: treating the disease and ignoring the symptom (Editorial). Diabetologia 39:1247–1248, 1996

14. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197, 1997

15. Alberti KGMM, Zimmet PZ, for the WHO Consultation Group: Definition, diagnosis and classification of diabetes mellitus and its complications. I. Diagnosis and classification of diabetes mellitus: provisional report of a WHO consultation. Diabet Med 15:539–553, 1998

16. National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039–1057, 1979

17. World Health Organization: WHO Expert Committee on Diabetes Mellitus. Second Report. Geneva, World Health Org., 1980 (Tech. Rep. Ser., no. 646)

18. Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA: Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 11:299–303, 1994

19. Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R: UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes: UK Prospective Diabetes Study Group. Lancet 350:1288–1293, 1997

20. World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. Geneva, World Health Org., 1985 (Tech. Rep. Ser., no. 727)

21. Engelgau MM, Thompson TJ, Herman WH, Boyle JP, Aubert RE, Kenny SJ, Badran A, Sous ES, Ali MA: Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes: diagnostic criteria and performance revisited. Diabetes Care 20:785–791, 1997

22. McCance DR, Hanson RL, Charles MA, Jacobsson LTH, Pettitt DJ, Bennett PH, Knowler WC: Comparison of tests for glycated haemoglobin and fasting and 2-hour glucose concentrations as diagnostic methods for diabetes. BMJ 308:1323–1328, 1994

23. Finch CF, Zimmet PZ, Alberti KGMM: Determining diabetes prevalence: a rational basis for the use of fasting plasma glucose concentrations? Diabet Med 7:603–610, 1990

24. Harris MI, Hadden WC, Knowler WC, Bennett PH: Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in the U.S. population aged 20–74 yr. Diabetes 36:523–534, 1987

25. Balkau B, Eschwege E, Tichet J, Marre M: Proposed criteria for the diagnosis of diabetes: evidence from a French epidemiological study. Diabetes Metab 23:428–434, 1997

26. Charles MA, Balkau B: Revision of diagnostic criteria for diabetes (Letter). Lancet 348:1657–1658, 1996

27. Cockram CS, Lau JTF, Chan AYW, Woo J, Swaminathan R: Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects. Diabetes Care 15:988–990, 1992

28. De Vegt F, Dekker JM, Stehouwer CDA, Nijpels G, Bouter LM, Heine RJ: The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance. Diabetes Care 21:1686–1690, 1998

29. DECODE Study Group: Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. BMJ 317:371–375, 1998

30. Shaw JE, de Courten M, Boyko EJ, Zimmet PZ: The impact on different populations of new diagnostic criteria for diabetes. Diabetes Care 22:762–766, 1999

31. Harris MI, Eastman RC, Cowie CC, Flegal KM, Eberhardt MS: Comparison of diabetes diagnostic categories in the US population according to 1997 American Diabetes Association and 1980–1985 World Health Organization diagnostic criteria. Diabetes Care 20:1859–1862, 1997

32. Unwin N, Alberti KGMM, Bhopal R, Harland J, Watson W, White M: Comparison of the current WHO and new ADA criteria for the diagnosis of diabetes mellitus in three ethnic groups in the UK. Diabet Med 15:554–557, 1998

33. Chang C-J, Wu J-S, Lu F-H, Lee H-L, Yang Y-C, Wen M-J: Fasting plasma glucose in screening for diabetes in the Taiwanese population. Diabetes Care 21:1856–1860, 1998

34. Gimeno SGA, Ferreira SRG, Franco LJ, Iunes M, the Japanese-Brazilian Diabetes Study Group: Comparison of glucose tolerance categories according to World Health Organization and American Diabetes Association diagnostic criteria in a population-based study in Brazil. Diabetes Care 21:1889–1892, 1998

35. Ko GTC, Chan JCN, Yeung VTF, Chow C-C, Tsang LWW, Li JKY, So W-Y, Wai HPS, Cockram CS: Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects. Diabetes Care 21:1221–1225, 1998

36. Wiener K, Roberts NB: The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects. Diabet Med 15:558–563, 1998

37. Gomez-Perez FJ, Aguilar-Salinas CA, Lopez-Alvarenga JC, Perez-Jauregui J, Guillen-Pineda LE, Rull JA: Lack of agreement between the World Health Organization category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose. Diabetes Care 21:1886–1888, 1998

38. Balkau B, Shipley M, Jarrett RJ, Pyorala K, Pyorala M, Forhan A, Eschwege E: High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. Diabetes Care 21:360–367, 1998

39. Barrett-Connor E, Ferrarra A: Isolated postchallenge hyperglycemia and the risk of fatal cardiovascular disease in older women and men. Diabetes Care 21:1236–1239, 1998

40. Bjornholt JV, Erikssen G, Aaser E, Sandvik L, Nitter-Hauge S, Jervell J, Erikssen J, Thaulow E: Fasting blood glucose: an underestimated risk factor for cardiovascular death. Diabetes Care 22:45–49, 1999

41. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, Wiedmeyer H-M, Byrd-Holt DD: Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in U.S. adults. Diabetes Care 21:518–524, 1998

42. CDC Diabetes Cost-Effectiveness Study Group: The cost-effectiveness of screening for type 2 diabetes. JAMA 280:1757–1763, 1998

43. U.K. Prospective Diabetes Study 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 352:837–853, 1998

44. U.K. Prospective Diabetes Study Group: Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865, 1998

45. Larsson H, Berglund G, Lindgarde F, Ahren B: Comparison of ADA and WHO criteria for diagnosis of diabetes and glucose intolerance. Diabetologia 21:1124–1125, 1998

46. Alberti KGMM: The clinical implications of impaired glucose tolerance. Diabet Med 13:927–937, 1996

47. Dowse GK, Zimmet PZ, King H: Relationship between prevalence of impaired glucose tolerance and NIDDM in a population. Diabetes Care 14:968–974, 1991

48. Shaw JE, Zimmet PZ, de Courten M, Dowse GK, Chitson P, Gareeboo H, Hemraj F, Fareeed D, Tuomilehto J, Alberti KGMM: Impaired fasting glucose or impaired glucose tolerance: what best predicts future diabetes? Diabetes Care 22:399–402, 1999


From the International Diabetes Institute and World Health Organization Collaborating Centre for the Epidemiology of Diabetes Mellitus, Melbourne, Victoria, Australia.

Address correspondence and reprint requests to Jonathan E. Shaw, MRCP, Specialist Registrar, Department of General Medicine, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M25 9LT, England. E-mail: jshotham@hotmail.com.

Received for publication 8 July 1999 and accepted in revised form 19 November 1999.

Abbreviations: ADA, American Diabetes Association; DECODE, Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe; FPG, fasting plasma glucose; ICA, islet cell antibodies; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; LADA, latent autoimmune diabetes in adults; NHANES III, Third National Health and Nutrition Examination Survey; OGTT, oral glucose tolerance test; PG, plasma glucose; UKPDS, U.K. Prospective Diabetes Study; WHO, World Health Organization.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Aventis Pharma.


Copyright © 2000 American Diabetes Association
Last updated: 3/00
For ADA Related Issues contact
CustomerService@diabetes.org

For Technical Issues contact webmaster@diabetes.org