NACB Home Page






Monitoring of Patients with Diabetes





Guidelines & Recommendations for Laboratory Analysis in the Diagnosis & Management of Diabetes Mellitus


Oral Glucose Tolerance Test (OGTT)

Jay McDonald, MD
University of Alabama
Birmingham, AL

1. Use. The oral glucose tolerance test (OGTT), once the gold standard for diagnosing diabetes mellitus, is now not recommended by the American Diabetes Association (ADA) for diagnosing either type 1 or type 2 diabetes, but continues to be recommended in a limited fashion by the World Health Organization (WHO) (1, 2). The oral glucose challenge (or glucose tolerance test) continues to be recommended by both the ADA and the WHO for establishing the diagnosis of gestational diabetes mellitus. In all cases, the extended 3-5 hour glucose tolerance test is not recommended for routine practice.

2. Rationale. Inability to respond appropriately to a glucose challenge, i.e., glucose intolerance, represents the fundamental defect in diabetes mellitus. The rationale for the ADA not recommending that the glucose tolerance test be used routinely to diagnose type 1 and 2 diabetes was that appropriate use of the FPG could identify approximately the same degree of glucose tolerance as the OGTT. Furthermore, in ordinary practice the OGTT is impractical. The consensus was that an OGTT with a 2h plasma glucose value of ³ 200 mg/dL (11.1 mmol/L) was the correct value for diagnosing diabetes mellitus because it corresponds to the value above which microangiopathy occurs (1). However, only approximately one-fourth of the individuals with 2h plasma glucose ³ 200 mg/dL (11.1 mmol/L) have a FPG of ³ 140 mg/dL (7.8 mmol/L), which was the FPG previously recommended to diagnose diabetes mellitus. The currently recommended FPG value of 126 mg/dL (7.0 mmol/L) was felt to correspond better to the GTT of 2h > 200 mg/dL, and thus correlate with development of complications.

There continues to be controversy over the use of the OGTT to classify individuals with impaired glucose tolerance and diabetes. Recent studies (3-6) indicate that individuals classified as having IGT by the OGTT (WHO criteria) have increased risk of cardiovascular disease but many of these individuals do not have IFG (ADA criteria). Furthermore, use of the OGTT and the WHO criteria to diagnose diabetes identifies approximately 2% more individuals as diabetic than if the ADA FPG criteria are used (7).

The 2h glucose tolerance test continues to be recommended for the diagnosis of gestational diabetes mellitus by both the ADA and WHO (1, 2). Deterioration of glucose tolerance occurs normally in pregnancy especially in the third trimester. Diagnosing and treating gestational diabetes is critical for preventing associated prenatal morbidity and mortality.

3. Analytical. The reproducibility of the OGTT has received considerable attention. In numerous studies, the reproducibility of the OGTT in classifying patients ranges from 50-66% (6). Possible reasons for lack of reproducibility include random variation of plasma glucose concentrations, the effects of administration of a hyperosmolar glucose solution on gastric emptying and effects of ambient temperature (8-11).

4. Interpretation.

a) For diagnosing type 1 and 2 diabetes, the ADA and WHO have different recommendations:

1) ADA: Not recommended for use (1).

2) WHO: When FPG levels fall in the range of IFG [6.1 mmol/L (110)-7.0 mmol/L (126)] an OGTT is recommended (2). After three days of unrestricted diet and an overnight fast (8-14 h), an FPG is obtained, following which 75g anhydrous glucose (or partial hydrolysates of starch of the equivalent carbohydrate) in 250-300 ml of water is taken orally over 5 min. For children, the load is 1.75g glucose/kg up to 75g glucose. Blood samples are collected 2 hr after the load, and plasma glucose analyzed. Results are interpreted as follows:




Impaired GT

< 7.0 mmol/L (126 mg/dL)

³ 7.8 (140) - < 11.1 (200)


³ 7.0 (126)

³ 11.1 (200)

Impaired Fasting

³ 6.1 (110) < 7.0 (126)

< 7.8 (140)

b) Gestational Diabetes Mellitus

1) ADA:

Screening should be performed between 24-28th week of gestation in women defined as at risk by the ADA (12). At risk patients are defined as:

³ 25 yo

< 25 yo and obese

Family history of diabetes in a first degree relative

Member of an ethnic/racial group with a high prevalence of diabetes.

The test recommended for screening is a 50g oral glucose load followed by a plasma glucose determination at 1h. A plasma glucose value ³ 7.8 mmol/L (140 mg/dL) indicates the need for definitive testing.

Definitive diagnosis is made by performing a 100g 3h OGTT. Two or more values must exceed:

mmol/L mg/dL

Fasting 5.8 105

1 h 10.5 190

2 h 9.2 165

3 h 8.0 145

2) WHO recommends the same test (75g OGTT) and diagnostic criteria as for type 1 and 2 diabetes mellitus (2).

5. Emerging considerations. The main issues of controversy are 1) the value of classifying individuals having impaired glucose tolerance (recommended by WHO but not the ADA) and 2) the appropriate use in gestational diabetes mellitus. The latter is particularly controversial. In the Fourth International Workshop Conference on Gestational Diabetes Mellitus (13), even tighter criteria (5-10% lower glucose values) than those accepted by the ADA were recommended for establishing the diagnosis. This discrepancy in recommendations reflects the state of knowledge about GDM, which continues to evolve with enhanced and expanded clinical research.

Intravenous Glucose Tolerance Test (IGTT):

Not recommended for routine use in the diagnosis and/or treatment of diabetes.

Urine Glucose:

1. Use. Semiquantitative urine glucose testing, once the hallmark of diabetes care in the home setting, has now been replaced by self monitoring of blood glucose. Semiquantitative urine glucose monitoring should only be considered for patients who can't or won't monitor their own blood glucose (14, 15).

2. Rationale. Although urine glucose correlates roughly with blood glucose, it provides no information about blood glucose levels below the variable renal glucose threshold [~ 10 mmol/L (180 mg/dL)]. This alone limits its usefulness for monitoring diabetes under modern care recommendations. Furthermore, the concentration of the urine affects urine glucose values and only average glucose values between voidings are reflected, further minimizing the value of urine glucose determinations.

3. Analytical. Semiquantitative test-strip methods utilizing specific reactions for glucose are recommended. Most commercially available strips utilize the glucose oxidase reaction. Test methods that detect reducing substances are not recommended due to numerous interferences, including numerous drugs, and non-glucose sugars. When used, single voided urine samples are recommended (15).

4. Interpretation/use. Because of the limited use of urine glucose determinations, semiquantitative specific reaction-based test strip methods are adequate.

5. Emerging considerations. None.

Non- or Minimally-Invasive Glucose Analyses:

1. Use/introduction. The need for a device for "continuous" in vivo monitoring of glucose levels in blood is a very high priority as patients are required to control their blood glucose more closely (1,16). Currently, there are only two devices that have been approved by the FDA for non- or minimally-invasive glucose sensing, the "Gluco Watch Biographer" (Cygnus), and the "Continuous Glucose Monitoring System" (MiniMed). Although promising, routine use of these devices cannot be recommended at this time because clinical studies remain limited.

2. Rationale. The first goal for developing a reliable in vivo glucose sensor is to detect unsuspected hypoglycemia. Emphasis on achieving this goal has become more intense since it became recognized that strict glucose control is accompanied by a marked increase in hypoglycemia (16). In contrast, a full range reliable in vivo glucose monitor is a prerequisite for development of an artificial pancreas that measures glucose and automatically adjusts insulin administration.

3. Analytical. The goal here is not to review comprehensively the status of research in this important area, but to make recommendations for current use. There have been a number of recent reviews on this topic (17, 18) and it has been the subject of national conferences. For example, non-invasive testing technology was the focus of the Oak Ridge Conference in 1999, with considerable attention being focused on glucose sensing technology (19) and a symposium at the 1999 American Diabetes Association meeting focused on non-invasive glucose sensing (20).

The technological advances in minimally or non-invasive glucose monitoring can generally be overviewed as shown in Table I.

Table I

Minimally and Non-invasive Methodology

For in vivo Glucose Monitoring (17)

1. Transcutaneous needle-type enzyme electrodes

2. Totally implanted sensors

· Enzyme electrodes

· Near infrared fluorescence based

3. Sampling technologies

· Microdialysis

· Reverse iontophoresis

4. Non-invasive technologies

· Near infrared spectroscopy

· Light scattering

· Photoacoustic spectroscopy

The transcutaneous sensors and implanted sensors employ similar detection systems including enzyme (usually glucose oxidase), electrodes and fluorescence-based techniques. Alternatives to enzymes as glucose recognition molecules are being developed, including artificial glucose "receptors" (21, 22). Fluorescence technologies include use of engineered molecules whose fluorescence intensity or spectrum changes upon binding glucose or use of competitive binding assays that employ two fluorescent molecules, so-called fluorescent resonance energy transfer (FRET) (23-27).

Different methods of tissue sampling "non-invasively" have been employed in various test systems. The general concept employed is that the concentration of glucose in the interstitial fluid will correlate with blood glucose. Most microdialysis systems are inserted subcutaneously (28-31). In contrast, "reverse iontophoresis", which is the basis of the FDA approved "Gluco Watch", (Cygnus) is "non-invasive" in concept. Iontophoresis employs a low level electrical current on the skin, which by convective transport (electro-osmosis) transports glucose across the skin. Then the concentration of glucose is measured by a glucose oxidase electrode detector (32, 33).

Finally, considerable research has been focused on developing totally non-invasive technology for glucose sensing. Of these, near infrared spectroscopy has been most intensively investigated, however, unpredictable spectral variations continue to hinder progress (34-38). Similar problems have hindered the successful use of light scattering (39, 40). Finally, photoacoustic spectroscopy, although less studied, has led to some encouraging preclinical results. In this technique, pulsed infrared light when absorbed by molecules results in detectable ultrasound waves, the intensity and patterns of which can theoretically be tuned to detect glucose (41-43).

4. Interpretation. Only the Gluco Watch Biographer (G-W) (Cygnus) and the Continuous Monitoring System (CMS) (Minimed) have received FDA approval. Therefore, only they will be considered here. The two devices have vastly differing applications. The G-W is designed to analyze "glucose" approximately three times/h for up to 12h, and appears best suited for detecting unsuspected hypoglycemia. In contrast, the CMS is intended for one-time or occasional use, rather than ongoing daily use. The information is intended to assist physicians help patients treat their diabetes, the values being downloaded into a computer in the physicians' offices.

The CMS consists of a glucose sensor inserted subcutaneously, which is connected to an externally worn monitor. Glucose is monitored every 5 min for up to 72 h and at the end of that period, the data are transferred to another computer for analyses. Values are not displayed on the externally worn monitor.

The Gluco Watch provides up to three readings/hour for as long as 12h after a single calibration. Calibration with reference blood glucose values requires a three-hour equilibration time and sampling time limits the number of measurements to approximately three/h. In limited, but promising, clinical trials, the Gluco Watch provides reasonable correlation with self glucose monitoring (32, 33). Despite the recent approval of the Gluco Watch by the FDA, its use has not been rigorously tested in a true clinically relevant home setting and it has not been tested in children. However, if it proves to reliably detect unsuspected hypoglycemic episodes in such settings, we should see widespread use of the Gluco Watch and continued improvement of the technology.

5. Emerging considerations. With the first approvals of self-monitoring non-invasive glucose sensors by the FDA, it is anticipated that there will be renewed efforts to bring other technologies forward into clinical studies. Ultimately, we will see improved methods for non-invasive or minimally-invasive glucose measurements that will complement current self glucose monitoring techniques.


1. The 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 1999;22:S5-S19.

2. Alberti KGMM, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539-553.

3. Gimeno SGA, Ferreira SRG, Franco LJ, Junes 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 1998;21:1889-1892.

4. Tominga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Fungata Diabetes Study. Diabetes Care 1999;22:920-924.

5. Perry RC, Baron AD. Impaired glucose tolerance. Why is it not a disease? Diabetes Care 1999;22:883-885.

6. Puavilai G, Chanprasertyotin S, Sriphrapradaeng A. Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. Diabetes Res Clin Pract 1999;44:21-26.

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

8. Ko GTC, Chan JCN, Woo J, Lau E, Yeung VTF, Chow C-C, Cockram CS. The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Ann Clin Biochem 1998;35:62-67.

9. Moses RG, Patterson MJ, Regan JM, Chaunchaiyakul R, Taylor NAS, Jenkins AB. A non-linear effect of ambient temperature on apparent glucose tolerance. Diabetes Res Clin Pract 1997;36:35-40.

10. Mooy JM, Grootenhuis PA, de Vries H, Kostense PJ, Popp-Snijders C, Bouter LM, Heine RJ. Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study. Diabetologia 1996;39:298-305.

11. Ganda OP, Day JL, Soeldner JS, Connon JJ, Gleason RE. Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests. Diabetes 1978;27:715-725.

12. American Diabetes Association. Gestational diabetes mellitus. Diabetes Care 1999;22:S74-S76.

13. American Diabetes Association. Proceedings of the fourth international workshop-conference on gestational diabetes mellitus. Diabetes Care 1998;21:B1-B161.

14. American Diabetes Association. Tests of glycemia in diabetes. Diabetes Care 1999;22:S77-S79.

15. Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM. Tests of glycemia in diabetes. Diabetes Care 1995;18:896-909.

16. DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986.

17. Pickup J, McCartney L, Rolinski O, Birch D. In vivo glucose sensing for diabetes management: progress towards non-invasive monitoring. BMJ 1999;319:1289-1292.

18. Khalil OS. Spectroscopic and clinical aspects of noninvasive glucose measurements. Clin Chem 1999;45:165-177.

19. Smith KM. Oak Ridge Conference 1999. Introduction. Clin Chem 1999;45:1586.

20. Bloomgarden ZT. American Diabetes Association Annual Meeting, 1999. New approaches to insulin treatment and glucose monitoring. Diabetes Care 1999;22:2078-2082.

21. Haupt K, Mosbach K. Plastic antibodies: developments and applications. Trends Biotechnol 1998;16:468-475.

22. Chen G, Guan Z, Chen C-T, Fu L, Sundaresan V, Arnold F. A glucose sensing polymer. Nature Biotechnol 1997;15:354-357.

23. James TC, Sananayake DRAS, Shinkai S. A glucose-selective molecular fluorescence sensor. Angewandte Chemie International Edition in English 1994;33:2207-2209.

24. Birch DJS, Imhof RE. Time-domain fluorescence spectroscopy using time-correlated single-photon counting. Topics in Fluorescence Spectroscopy 1994;1:1-95.

25. Tolosa L, Szmacinski H, Rao G, Lakowicz JR. Lifetime-based sensing of glucose using energy transfer with a long-lifetime donor. Anal Biochem 1997;250:102-108.

26. Rolinski OJ, Birch DJS, McCartney LJ, Pickup JC. Near-infrared assay for glucose determination. Soc Photo-optical Instrumentation Engineers Proc 1999;3602-6-14.

27. Marvin JS, Hellinga HW. Engineering biosensors by introducing fluorescent allosteric signal transducers: construction of a novel glucose sensor. J Am Chem Soc 1998;120:7-11.

28. Bolinder J, Ungerstedt U, Arner P. Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients. Diabetologia 1992;35:1177-1180.

29. Meyerhof C, Bischof F, Sternberg F, Zier H, Pfeiffer EF. On line continuous monitoring of subcutaneous tissue glucose in men by combining portable glucosensor with microdialysis. Diabetologia 1992;35:1087-1092.

30. Hashiguchi Y, Sakakida M. Nishida K, Uemura T, Kajiwara K-I, Shichiri M. Development of a miniaturised glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method. Diabetes Care 1994;17:387-396.

31. Hoss U, Gessler R, Kalatz B, Salgado MI, Sternberg F, Fussganger R. Calibration-free continuous on-line glucose monitoring: the comparative microdialysis technique. Diabetologia 1998;41(suppl 1):45A.

32. Tamada JA, Garg S, Jovanovic L, Pitzer KR, Fermi S, Potts RO, the Cygnus Research Team. Noninvasive glucose monitoring. Comprehensive clinical results. JAMA 1999;282:1839-1844.

33. Garg SK, Potts RO, Ackerman NR, Fermi SJ, Tamada JA, Chase HP. Correlation of fingerstick blood glucose measurements with GlucoWatch biographer glucose results in young subjects with type 1 diabetes. Diabetes Care 1999;22:1708-1714.

34. Arnold MA. Non-invasive glucose monitoring. Curr Opin Biotechnol 1998;16-43-45.

35. Robinson MR, Eaton RP, Haaland DM, Koepp GW, Thomas EV, Stallard BR, et al. Non-invasive glucose monitoring in diabetic patients: a preliminary evaluation. Clin Chem 1992;38:1618-1622.

36. Marbach R, Koschinski T, Gries FA, Heise HM. Non-invasive blood glucose assay by near-infrared diffuse reflectance spectroscopy of the human lip. Applied Spectroscopy 1993;47:875-881.

37. Kajiwara K, Uemura T, Kishikawa H, Nishida K, Hashiguchi Y, Uehara M, et al. Non-invasive measurement of blood glucose concentrations by analysing Fourier transform infra-red absorbance spectra though oral mucosa. Med Biol Eng Comput 1993;31:S17-S22.

38. Gabriely I, Wozniak R, Mevorach M, Kaplan J, Aharon Y, Shamoon H. Transcutaneous glucose measurement using near-infrared spectroscopy during hypoglycemia. Diabetes Care 1999;22:2026-2032.

39. Maier JS, Walker SA, Fantini S, Franceschini MA, Gratton E. Possible correlation between blood glucose concentration and the reduced light scattering coefficient of tissues in the near infrared. Optics Lett 1994:19:2062-2064.

40. Heinemann L, Schmelzeise Redeker G. Non-invasive continuous glucose monitoring in type 1 diabetic patients with optical glucose sensors. Diabetologia 1998;41:848-854.

41. Christison GB, MacKenzie HS. Laser photoacoustic determination of physiological glucose concentrations in human blood. Med Biol Comput 1993;31:284-290.

42. MacKenzie HA, Ashton HS, Shen YC, Lindberg J, Rae P, Quan KM, et al. Blood glucose measurements by photoacoustics. Biomed Optical Spectroscopy Diagnostics 1998;22:156-159.

43. MacKenzie HA, Ashton HS, Spiers S, Shen Y, Freeborn SS, Hannigan J, Lindberg J, Rae P. Advances in photoacoustic noninvasive glucose testing. Clin Chem 1999;45:1587-1595.