eMedicine Specialties > Endocrinology > Diabetes Mellitus

Glucose Intolerance: Differential Diagnoses & Workup

Author: Samuel T Olatunbosun, MD, FACP, Chief, Internal Medicine, 56th Medical Group, Luke Air Force Base
Coauthor(s): Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP, Professor of Medicine, Program Director, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center
Contributor Information and Disclosures

Updated: Aug 5, 2009

Differential Diagnoses

Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Insulin Resistance

Workup

Laboratory Studies

  • Plasma glucose measurement is used as a screening test and for confirmation of a previously detected abnormality of glucose tolerance. Fasting plasma glucose studies are the preferred diagnostic test of the ADA. A random plasma glucose measurement in the presence of classic diabetes symptoms is also acceptable.
  • Oral glucose tolerance test
    • The standard oral glucose tolerance test (OGTT) involves measurement of plasma glucose concentration 2 hours after a 75-g oral glucose load. It is seldom used as a confirmatory test in the diagnosis of diabetes. However, OGTT may be helpful in situations in which fasting or random glucose results are equivocal. It is required in order to diagnose impaired glucose tolerance (IGT), although it is increasingly being reserved for research purposes.
    • A provisional diagnosis of diabetes must be confirmed on a subsequent day by any of the 3 methods, ie, fasting, casual, and OGTT.
    • The ADA diagnostic criteria, which emphasizes fasting plasma glucose, facilitates the screening of individuals with undiagnosed diabetes, but the criteria help to identify fewer people with diabetes when compared with OGTT.
    • The ADA diagnostic criteria include the following:
      • Normal glucose homeostasis - Fasting plasma glucose (FPG) level of less than 100 mg/dL and 2-hour OGTT result of less than 140 mg/dL after a 75-g oral glucose load
      • Impaired fasting glucose - Fasting plasma glucose level of 100 mg/dL or greater but less than 126 mg/dL, based on ADA criteria (The cutpoint for impaired fasting glucose levels has been reduced from 110 mg/dL by the ADA, with the aim of identifying more individuals who are at risk for developing diabetes.) 
      • Impaired glucose tolerance - Two-hour OGTT result of 140 mg/dL or greater but less than 200 mg/dL
      • Diabetes mellitus - (1) FPG level of 126 mg/dL or greater and a casual plasma glucose level of 200 mg/dL or greater, (2) a casual plasma glucose level of 200 mg/dL or greater on 2 occasions, or (3) the classic symptoms plus a 2-hour OGTT result of 200 mg/dL or greater
      • Gestational diabetes mellitus - Defined as any degree of glucose intolerance with onset or first recognition during pregnancy. In the United States, the most popular screening test for gestational diabetes mellitus is a 1-hour plasma glucose measurement after a 50-g oral glucose load followed by (if necessary) 3-hour diagnostic testing using a 100-g load. The WHO-recommended procedure using a 75-g oral glucose load is used in many parts of the world.  
  • Screening tests for type 2 diabetes should be considered at 3-year intervals in all individuals older than 45 years, particularly if the BMI is 25 kg/m2 or higher. Testing is indicated at a younger age or more frequently in individuals who are overweight (BMI 25 kg/m2 or higher) and have additional risk factors, including the following:
    • Habitual physical inactivity
    • First-degree relation to a person with diabetes 
    • High-risk ethnic background - Such as Hispanic, American Indian, Asian American, African American, or Pacific Islander
    • Delivery of a baby that is large for its gestational age (baby >9 lb) or history of gestational diabetes mellitus 
    • Hypertension - Blood pressure of 140/90 mm Hg or greater, or on therapy for diabetes
    • High-density lipoprotein cholesterol level of 35 mg/dL or less, triglyceride level of 250 mg/dL or more, or both 
    • Polycystic ovary syndrome (PCOS) 
    • IGT or impaired fasting glucose, as determined with previous testing 
    • Other clinical conditions associated with insulin resistance - Such as severe obesity and acanthosis nigricans
    • History of cardiovascular disease 
  • In the absence of the above criteria, testing for prediabetes and diabetes should begin at age 45 years.
  • If results are normal, testing should be repeated at least every 3 years, with consideration of more frequent testing depending on initial results and risk status.
  • Urinalysis is important, because ketonuria and massive glycosuria are indicators of acute decompensation. Significant proteinuria may be present in patients with diabetic nephropathy. Abnormalities are found in specific gravity, and pH can be found in uremia.
  • Urine microalbumin is a marker of early renal impairment and endothelial dysfunction.
  • Glycated hemoglobin is not recommended as a diagnostic tool. It serves as an index of severity of hyperglycemia over 6-8 weeks preceding measurement. This is highly specific as evidence of chronic hyperglycemia. It is a predictor of chronic complications.
  • Serum electrolytes, BUN, creatinine, uric acid, and blood gases are evaluated, because during acute decompensation, metabolic derangement from loss of water, sodium, potassium, other electrolytes, anion gap, and osmolality abnormalities are very common. Normal renal and hepatic function must be confirmed before therapy is started with some oral antidiabetic agents.
  • Liver function tests assessing baseline liver function are used to exclude hepatic disease prior to commencing certain antihyperglycemic agents (eg, biguanides, thiazolidinediones). Periodic measurements are required during treatment with thiazolidinediones. Liver cirrhosis is a cause of glucose intolerance.
  • A lipid profile is necessary, because an increased triglyceride level may be present. This is often a reflection of poor glycemic control and may normalize on attainment of euglycemia. Other lipid abnormalities, such as increased total cholesterol and low-density lipoprotein levels, are commonly found.
  • A complete blood cell (CBC) count is obtained, because an increased white blood cell count is common during acute infection. Ketoacidosis also is a cause of leukocytosis.
  • A C-peptide profile is needed, because an undetectable plasma level indicates type 1 diabetes (in the absence of hypoglycemia). C-peptide profiling may also be helpful in deciding treatment in some cases of type 2 diabetes. It is not routinely used in clinical practice.
  • Increased levels of plasma plasminogen activator inhibitor type 1, a marker of impaired fibrinolysis, are frequently found in patients with glucose intolerance and are a correlate of insulin resistance syndrome.
  • An increased plasma homocysteine level is a risk factor for atherosclerosis. The homocysteine level should therefore be measured in selected patients.

Other Tests

  • Electrocardiography (ECG) and other cardiac workup

    • Perform ECG and other tests depending on the patient's cardiovascular risk profile.
    • Features of left ventricular hypertrophy and/or cardiomegaly are common in patients with hypertension.
    • Low-risk patients may have normal test results, whereas, with appropriate cardiac testing, patients with significant cardiovascular disease may show evidence of ischemia.

More on Glucose Intolerance

Overview: Glucose Intolerance
Differential Diagnoses & Workup: Glucose Intolerance
Treatment & Medication: Glucose Intolerance
Follow-up: Glucose Intolerance
Multimedia: Glucose Intolerance
References
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References

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. Jan 2008;31 Suppl 1:S55-60. [Medline].

  2. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. Mar 2005;115(3):485-91. [Medline]. [Full Text].

  3. Cooper DH, Krainik AJ, Lubner SJ, et al, eds. The Washington Manual of Medical Therapeutics. Philadelphia, Pa: Lippincott Williams & Wilkins; 2007.

  4. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008.

  5. Corpeleijn E, Mensink M, Kooi ME, et al. Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss. Obesity (Silver Spring). May 2008;16(5):1025-32. [Medline].

  6. Dagogo-Jack S, Santiago JV. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch Intern Med. Sep 8 1997;157(16):1802-17. [Medline].

  7. Ahren B. [New strategy in type 2 diabetes tested in clinical trials. Glucagon-like peptide 1 (GLP-1) affects basic caused of the disease]. Lakartidningen. 2005;102(8):545-9. [Medline].

  8. Bock G, Dalla Man C, Campioni M, et al. Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance. Diabetes. Dec 2006;55(12):3536-49. [Medline]. [Full Text].

  9. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health and Nutrition Examination Survey 1999-2002. Diabetes Care. Jun 2006;29(6):1263-8. [Medline]. [Full Text].

  10. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988-1994. Diabetes Care. Apr 1998;21(4):518-24. [Medline]. [Full Text].

  11. King H, Rewers M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care. 1993;16(1):157-77. [Medline].

  12. Færch K, Vaag A, Holst JJ, et al. Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action. Diabetologia. May 2008;51(5):853-861. [Medline].

  13. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. Mar 2007;30(3):753-9. [Medline].

  14. American Diabetes Association. Standards of medical care in diabetes--2008. Diabetes Care. Jan 2008;31 Suppl 1:S12-54. [Medline].

  15. Bourn DM, Mann JI, McSkimming BJ, et al. Impaired glucose tolerance and NIDDM: does a lifestyle intervention program have an effect?. Diabetes Care. Nov 1994;17(11):1311-9. [Medline].

  16. [Best Evidence] Gillies CL, Abrams KR, Lambert PC, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. Feb 10 2007;334(7588):299. [Medline].

  17. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303. [Medline].

  18. Du H, van der A DL, van Bakel MM, et al. Glycemic index and glycemic load in relation to food and nutrient intake and metabolic risk factors in a Dutch population. Am J Clin Nutr. Mar 2008;87(3):655-61. [Medline].

  19. Pham DQ, Nogid A, Plakogiannis R. Sitagliptin: a novel agent for the management of type 2 diabetes mellitus. Am J Health Syst Pharm. Mar 15 2008;65(6):521-31. [Medline].

  20. Mest HJ, Mentlein R. Dipeptidyl peptidase inhibitors as new drugs for the treatment of type 2 diabetes. Diabetologia. Apr 2005;48(4):616-20. [Medline].

  21. Ceriello A, Piconi L, Quagliaro L, et al. Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes. Diabetes Care. Mar 2005;28(3):632-7. [Medline].

  22. Hollander P, Ratner R, Fineman M, et al. Addition of pramlintide to insulin therapy lowers HbA1c in conjunction with weight loss in patients with type 2 diabetes approaching glycaemic targets. Diabetes Obes Metab. Nov 2003;5(6):408-14. [Medline].

  23. Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. Nov 2004;21(11):1204-12. [Medline].

  24. Riddle M, Frias J, Zhang B, et al. Pramlintide improved glycemic control and reduced weight in patients with type 2 diabetes using basal insulin. Diabetes Care. Nov 2007;30(11):2794-9. [Medline]. [Full Text].

  25. Weyer C, Fineman MS, Strobel S, et al. Properties of pramlintide and insulin upon mixing. Am J Health Syst Pharm. Apr 15 2005;62(8):816-22. [Medline].

  26. Wysham C, Lush C, Zhang B, et al. Effect of pramlintide as an adjunct to basal insulin on markers of cardiovascular risk in patients with type 2 diabetes. Curr Med Res Opin. Jan 2008;24(1):79-85. [Medline].

  27. Ahrén B, Pacini G. Islet adaptation to insulin resistance: mechanisms and implications for intervention. Diabetes Obes Metab. Jan 2005;7(1):2-8. [Medline].

  28. Ahrén B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res. Nov-Dec 2004;36(11-12):867-76. [Medline].

  29. Alberti KG. Impaired glucose tolerance: what are the clinical implications?. Diabetes Res Clin Pract. 1998;40 Suppl:S3-8. [Medline].

  30. Blake DR, Meigs JB, Muller DC, et al. Impaired glucose tolerance, but not impaired fasting glucose, is associated with increased levels of coronary heart disease risk factors: results from the Baltimore Longitudinal Study on Aging. Diabetes. Aug 2004;53(8):2095-100. [Medline]. [Full Text].

  31. Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. Jan-Feb 2006;12 Suppl 1:25-30. [Medline].

  32. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. Jul 2004;88(4):787-835, ix. [Medline].

  33. Diamant M, Bunck MC, Heine RJ. [Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2]. Ned Tijdschr Geneeskd. Sep 25 2004;148(39):1912-7. [Medline].

  34. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. Sep 12 1998;352(9131):854-65. [Medline].

  35. Einhorn D, Reaven GM, Cobin RH, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. May-Jun 2003;9(3):237-52. [Medline].

  36. Festa A, D'Agostino R Jr, Hanley AJ, et al. Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. Diabetes. Jun 2004;53(6):1549-55. [Medline]. [Full Text].

  37. Flier JS. Syndromes of insulin resistance. In: Becker KL, ed. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: Lippincott; 1249-59.

  38. Gerich JE. Postprandial hyperglycemia and cardiovascular disease. Endocr Pract. Jan-Feb 2006;12 Suppl 1:47-51. [Medline].

  39. Hanefeld M, Temelkova-Kurktschiev T, Schaper F, et al. Impaired fasting glucose is not a risk factor for atherosclerosis. Diabet Med. Mar 1999;16(3):212-8. [Medline].

  40. Henry RR. Thiazolidinediones. Endocrinol Metab Clin North Am. 1997;26(3):553-73. [Medline].

  41. [Best Evidence] Herman WH, Hoerger TJ, Brandle M, et al. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Ann Intern Med. Mar 1 2005;142(5):323-32. [Medline].

  42. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. Sep 12 1998;352(9131):837-53. [Medline].

  43. Joy SV, Rodgers PT, Scates AC. Incretin mimetics as emerging treatments for type 2 diabetes. Ann Pharmacother. Jan 2005;39(1):110-8. [Medline].

  44. Koska J, DelParigi A, de Courten B, et al. Pancreatic polypeptide is involved in the regulation of body weight in pima Indian male subjects. Diabetes. Dec 2004;53(12):3091-6. [Medline]. [Full Text].

  45. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385-411. [Medline].

  46. Li CL, Pan CY, Lu JM, et al. Effect of metformin on patients with impaired glucose tolerance. Diabet Med. Jun 1999;16(6):477-81. [Medline].

  47. McIntosh CH, Demuth HU, Pospisilik JA, et al. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents?. Regul Pept. Jun 15 2005;128(2):159-65. [Medline].

  48. Muscelli E, Mari A, Natali A, et al. Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab. Dec 2006;291(6):E1144-50. [Medline]. [Full Text].

  49. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 1979;28(12):1039-57. [Medline].

  50. Nauck MA, Meier JJ. Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept. Jun 15 2005;128(2):135-48. [Medline].

  51. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19 Suppl 1:1-93. [Medline].

  52. [Best Evidence] Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. Jun 14 2007;356(24):2457-71. [Medline]. [Full Text].

  53. Olatunbosun ST. Diagnosis and follow-up of subjects with impaired glucose tolerance: how reliable is OGTT? Report from a Nigerian survey. Diabetes Res Clin Pract. Aug 1998;41(2):147-8. [Medline].

  54. Ratner RE,. An update on the Diabetes Prevention Program. Endocr Pract. Jan-Feb 2006;12 Suppl 1:20-4. [Medline]. [Full Text].

  55. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-607. [Medline].

  56. Reaven GM. Insulin resistance and its consequences: non-insulin-dependent diabetes mellitus and coronary heart disease. In: Leroith D, ed. Diabetes Mellitus: A Fundamental and Clinical Text. Philadelphia, Pa: Lippincott-Raven; 1996:509-19.

  57. Report of a WHO Study Group. Diabetes mellitus. World Health Organ Tech Rep Ser. 1985;1-113. [Medline].

  58. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. Jul 1997;20(7):1183-97. [Medline].

  59. Sjöström L. Analysis of the XENDOS study (Xenical in the Prevention of Diabetes in Obese Subjects). Endocr Pract. Jan-Feb 2006;12 Suppl 1:31-3. [Medline].

  60. Suzuki H, Fukushima M, Usami M, et al. IGT with fasting hyperglycemia is more strongly associated with microalbuminuria than IGT without fasting hyperglycemia. Diabetes Res Clin Pract. Jun 2004;64(3):213-9. [Medline].

  61. Tai ES, Goh SY, Lee JJ, et al. Lowering the criterion for impaired fasting glucose: impact on disease prevalence and associated risk of diabetes and ischemic heart disease. Diabetes Care. Jul 2004;27(7):1728-34. [Medline]. [Full Text].

  62. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. Sep 30 1993;329(14):977-86. [Medline].

  63. Vella A, Camilleri M, Rizza RA. The gastrointestinal tract and glucose tolerance. Curr Opin Clin Nutr Metab Care. Jul 2004;7(4):479-84. [Medline].

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Further Reading

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Keywords

glucose intolerance, abnormal glucose tolerance, abnormal glucose homeostasis, disorders of glucose tolerance, disorders of glycemia, glucose tolerance, type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, GDM, impaired glucose tolerance, IGT, impaired fasting glucose, IFG, insulin resistance, hyperglycemia, normoglycemia, ketoacidosis, dysmetabolic syndrome, central adiposity, pancreas, pancreatic function, hypoglycemia, pancreatic beta cells

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Contributor Information and Disclosures

Author

Samuel T Olatunbosun, MD, FACP, Chief, Internal Medicine, 56th Medical Group, Luke Air Force Base
Samuel T Olatunbosun, MD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, and American Diabetes Association
Disclosure: Nothing to disclose.

Coauthor(s)

Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP, Professor of Medicine, Program Director, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center
Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, and Royal College of Physicians
Disclosure: Eli Lilly None Speaking and teaching; GlaxoSmithKline None Speaking and teaching; Merck None Speaking and teaching

Medical Editor

David S Schade, MD, Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center
David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, and Society for Experimental Biology and Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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