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Glucose Intolerance

  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
 
Updated: Sep 14, 2015
 

Background

Several distinct disorders of glucose tolerance exist. The most widely used classification of diabetes mellitus (DM) and allied categories of glucose intolerance is that recommended by the World Health Organization (WHO) in 1985. The American Diabetes Association (ADA), however, proposed a system based on disease etiology instead of the type of pharmacologic treatment.[1]  (See Etiology and Clinical Presentation.)

The major categories of the disorders of glycemia or glucose tolerance are as follows:

  • Type 1 DM
  • Type 2 DM
  • Other specific types of diabetes
  • Gestational DM [2]
  • Impaired glucose tolerance
  • Impaired fasting glucose

Conditions secondarily associated with glucose intolerance also occur. Etiologic types and stages of the major disorders of glucose intolerance are shown in the image below (see also Etiology and Clinical Presentation).

Etiologic types and stages of the major disorders Etiologic types and stages of the major disorders of glucose tolerance.

In most cases, the diagnosis of a type of diabetes or glucose intolerance is based on the patient’s condition at the time, but not all patients have a set of symptoms that fit readily into a particular class (see Clinical Presentation).

When hyperglycemia is present, its severity may change in time, depending on the underlying process. Choosing an appropriate management approach to any disorders of glucose intolerance necessitates a strong understanding of the mechanisms involved in the disease process.[3, 4] (See Treatment and Management, as well as Medication.)

The total annual economic cost (direct and indirect) of diabetes in the United States is at least $132 billion. The overall cost of all categories of glucose tolerance and related cardiovascular risk factors exceeds this estimate.

For more information, see Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2.

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Pathophysiology

Heterogeneity occurs in most glucose intolerance disorders, including diabetes mellitus syndromes.

Type 1 diabetes mellitus

Type 1 diabetes mellitus is characterized by absolute insulin deficiency. In type 1A, a cellular-mediated autoimmune destruction of beta cells of the pancreas occurs. The disease process is initiated by an environmental factor—that is, an infectious or noninfectious agent in genetically susceptible individuals.

Some genes in the histocompatibility leukocyte antigen (HLA) system are thought to be crucial. A stress-induced epinephrine release, which inhibits insulin release (with resultant hyperglycemia), sometimes occurs and may be followed by a transient asymptomatic period known as "the honeymoon." Lasting weeks to months, the honeymoon precedes the onset of overt, permanent diabetes.

Amylin, a beta-cell hormone that is normally cosecreted with insulin in response to meals, is also completely deficient in persons with type 1 diabetes mellitus. Amylin exhibits several glucoregulatory effects that complement those of insulin in postprandial glucose regulation. Idiopathic forms of type 1 diabetes also occur, without evidence of autoimmunity or HLA association; this subset is termed type 1B diabetes.

Type 2 diabetes mellitus

In a state of health, normoglycemia is maintained by fine hormonal regulation of peripheral glucose uptake and hepatic production. Type 2 diabetes mellitus results from a defect in insulin secretion and an impairment of insulin action in hepatic and peripheral tissues, especially muscle tissue and adipocytes.[5] A postreceptor defect is also present, causing resistance to the stimulatory effect of insulin on glucose use. As a result, a relative insulin deficiency develops, unlike the absolute deficiency found in patients with type 1 diabetes. The specific etiologic factors are not known, but genetic input is much stronger in type 2 diabetes than in the type 1 form.[6]

Impaired glucose tolerance (IGT) is a transitional state from normoglycemia to frank diabetes, but patients with impaired glucose tolerance exhibit considerable heterogeneity. Type 2 diabetes, or glucose intolerance, is part of a dysmetabolic syndrome (syndrome X) that includes insulin resistance, hyperinsulinemia, obesity, hypertension, and dyslipidemia. Current knowledge suggests that the development of glucose intolerance or diabetes is initiated by insulin resistance and worsened by the compensatory hyperinsulinemia.

The progression to type 2 diabetes is influenced by genetics and environmental or acquired factors, such as a sedentary lifestyle and dietary habits that promote obesity. Most patients with type 2 diabetes are obese, and obesity is associated with insulin resistance. Central adiposity is more important than increased generalized fat distribution. In patients with frank diabetes, glucose toxicity and lipotoxicity may further impair insulin secretion by the beta cells.[7, 8, 9, 10]

Gestational diabetes mellitus

Gestational diabetes mellitus (GDM) was previously described as any degree of glucose intolerance in which onset or first recognition occurs during pregnancy.[2] The definition was limited by imprecision. Women diagnosed with diabetes in the first trimester are now classified as having type diabetes. GDM is diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes. Insulin requirements are increased during pregnancy because of the presence of insulin antagonists, such as human placental lactogen or chorionic somatomammotropin, and cortisol; these promote lipolysis and decrease glucose use.

Another factor in increased insulin requirements during pregnancy is the production of insulinase by the placenta. Various genetic defects of the beta cell, insulin action, diseases of the exocrine pancreas, endocrinopathies, drugs, chemical agents, infections, immune disorders, and genetic syndromes can cause variable degrees of glucose intolerance, including diabetes.

To see complete information on Diabetes Mellitus and Pregnancy, please go to the main article by clicking here.

Other specific types of diabetes mellitus

These are specific types of diabetes due to other causes, which include monogenic diabetes syndromes, diseases of the exocrine pancreas, and drug- or chemical induced diabetes.  Various genetic defects of the beta cell, insulin action, diseases of the exocrine pancreas, endocrinopathies, drugs, chemical agents, infections, immune disorders, and genetic syndromes can cause variable degrees of glucose intolerance, including diabetes.

Varying forms of glucose intolerance

Glucose intolerance may be present in many patients with cirrhosis due to decreased hepatic glucose uptake and glycogen synthesis. Other underlying mechanisms include hepatic and peripheral resistance to insulin and serum hormonal abnormalities. Abnormal glucose homeostasis may also occur in uremia, as a result of increased peripheral resistance to the action of insulin.

The gastrointestinal tract plays a significant role in glucose tolerance.[11] With food ingestion, incretin hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesized and secreted by specialized gut cells. Oral glucose administration results in a higher insulin secretory response than does intravenous glucose administration; this difference is due in part to incretin hormones.

The significance of incretin hormones has been noted as a result of efforts to develop agents that may improve glycemic control in patients with type 2 diabetes through new mechanisms.[12] These strategies include inhibition of dipeptidyl peptidase IV (DPP-4), the major enzyme responsible for degrading incretin hormones in vivo, and the use of GLP-1 agonists.[13] Incretin hormones also significantly affect the differentiation, mitogenesis, and survival of beta cells.

Pathologic defects observed in type 2 diabetes mellitus and sometimes in impaired glucose tolerance include postprandial hyperglucagonemia, dysregulation of gastric emptying, and loss of incretin effect.

Postprandial hyperglycemia in diabetes and impaired glucose tolerance (IGT) is related to a lower rate of glucose disposal, whereas insulin secretion and action, as well as postprandial turnover, are essentially normal in individuals with isolated IGT.[14]

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Etiology

Genetic defects of beta-cell function include the following:

  • Mutation on chromosome 12, the hepatocyte nuclear factor (HNF-1) alpha - MODY3
  • Mutation on chromosome 7p, the glucokinase gene - MODY2
  • Mutation on chromosome 20, HNF-4 alpha - MODY1
  • Point mutations in mitochondrial DNA

Defects in insulin action include the following:

  • Structure and function of insulin receptor: postreceptor signal transduction pathways
  • Type A insulin resistance
  • Leprechaunism
  • Rabson-Mendenhall syndrome
  • Lipoatrophic diabetes

Diseases of the exocrine pancreas include the following:

(Note that the malnutrition-related diabetes has been eliminated from the above list, as evidence is lacking on protein deficiency as a direct cause of diabetes, and fibrocalculous pancreatopathy has been reclassified as a disease of the exocrine pancreas.)

Endocrine diseases associated with excess production of insulin antagonists include the following:

Drugs or chemical agents with adverse effects on glucose tolerance include the following:

  • Thiazides
  • Diazoxide
  • Glucocorticoids
  • Calcineurin inhibitors, such as cyclosporine and tacrolimus
  • Oral contraceptives
  • Beta-adrenergic agonists
  • Nicotinic acid
  • Thyroid hormone
  • Pentamidine
  • Alpha interferon
  • Atypical antipsychotics, especially clozapine and olanzapine
  • Antiretroviral drugs
  • Vacor

Infections associated with beta-cell destruction include the following:

  • Rubella
  • Coxsackievirus B
  • Mumps
  • Cytomegalovirus
  • Adenovirus

Genetic syndromes that predispose an individual to impaired glucose tolerance include the following:

  • Klinefelter syndrome
  • Turner syndrome
  • Wolfram syndrome
  • Friedreich ataxia

Pregnancy can be associated with gestational diabetes mellitus, and the risk of diabetes increases with parity.

Obesity is a powerful determinant of glucose intolerance in the general population and develops through the interaction of genetics and acquired factors such as physical inactivity and dietary habits.

Immune-mediated causes of impaired glucose tolerance include stiff person syndrome and anti-insulin receptor abnormalities. Other causes of glucose intolerance are liver disease (as in cirrhosis) and renal failure.

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Epidemiology

United States statistics

Approximately 19.3 million (9.3%) people in the United States have diabetes; nearly 6 million of these cases are undiagnosed.[15, 16]

Impaired glucose tolerance (IGT), considered the most common form of glucose intolerance in the United States, is present in 11% of the general population. Prevalence of impaired fasting glucose is 6.9% (13.4 million Americans).[16] According to the American Dietetic Association, however, a review of previous data using a new diagnostic criterion for impaired fasting glucose revised the statistics to 41 million Americans in the 2 categories combined, with 16 million Americans in the IGT category alone.

Type 1 diabetes, which usually occurs in children and adolescents, accounts for 5-10% of diabetes cases. Approximately 1 out of every 400-500 children and adolescents in the United States has type 1 diabetes.

Type 2 diabetes, which most commonly occurs in middle age, is the predominant form of clinical disease, constituting 90-95% of cases. This type of diabetes is reaching epidemic proportions. Minority populations, especially American Indians, Hispanic persons, African Americans, and Asian Americans are at particularly high risk.

Gestational diabetes develops in approximately 4% of pregnancies in the United States. The prevalence is 1-14%, depending on the population studied and the diagnostic criteria.

International statistics

The lowest prevalence rates of diabetes (< 1%) are found in certain African and Chinese populations and in rural populations of the Mapuche Indians of Chile. The highest prevalence rates of type 2 diabetes in patients older than 30 years are found in the Pima Indians of Arizona and in the Nauran people of the Pacific island of Nauru. The prevalence rates of these populations are 50%[17] and 35%, respectively. The risk in other populations is classified as ranging from low to high-medium.

The overall range for impaired glucose tolerance (IGT; 1-25%) is considerable, though not as wide as for diabetes (0-50%). IGT is rare in Mapuche Indians but common in many other population groups. Generally, residents of developing nations and migrant or ethnic minorities in industrialized countries are at higher risk for diabetes and IGT.

Race characteristics

Native Americans and certain Pacific island populations have the highest risk for glucose intolerance. African Americans and Hispanics have higher rates of glucose intolerance than do non-Hispanic whites.

Whites have the highest rates of type 1 diabetes, especially those of northern European descent. The disease is unknown or rare among certain ethnic groups (eg, Japanese, Chinese, African).

Type 2 diabetes is more prevalent in ethnic minorities, while type 1 diabetes occurs with higher frequencies in whites, especially those of northern European descent.

Type 1B diabetes is more common in patients of Asian or African origin.

Sex characteristics

In the World Health Organization’s global data, the prevalence ratio of diabetes for men and women varies markedly, with no consistent trend; however, impaired glucose tolerance is more common in women than in men. The relative difference in frequency between the sexes is probably related to the presence of underlying factors such as pregnancy and obesity, rather than to a sex-specific genetic tendency.[18]

Age characteristics

Type 1 diabetes occurs most commonly in children and adolescents but may occur in individuals of any age. Type 2 diabetes typically begins in middle life or later, usually after age 30 years; its prevalence rises with age. Maturity-onset diabetes of youth can be expressed in childhood or in early adolescence.

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Prognosis

Several studies have demonstrated a relationship between high plasma glucose distributions and the risk for cardiovascular disease and increased mortality, even within the normoglycemic range.[19, 20, 21, 22, 23, 24]

Diabetes is the sixth leading cause of death by disease worldwide and the seventh leading cause of death in the United States. Those with impaired glucose tolerance have a propensity for acute metabolic complications. IGT is a leading cause of end-stage renal disease and of blindness. Individuals with this condition also are at higher risk for neuropathy and gangrene.

Gestational diabetes

Gestational diabetes mellitus brings an increased risk for fetal and neonatal morbidity and mortality, as well as obstetric complications. There is an associated increased risk for obesity in offspring, as well as for glucose intolerance and type 2 diabetes.[23, 25, 24]

For gestational diabetes mellitus, reclassification is performed at 6-12 weeks postpartum. In most patients with gestational DM, glucose tolerance becomes normal after delivery. The lifetime risk for IGT and diabetes is increased substantially in these women, however.

Impaired glucose tolerance

Impaired glucose tolerance (IGT) is a major risk factor for diabetes, with 20-50% of affected persons progressing to diabetes within 10 years. Approximately one third revert to normal glucose tolerance, while others persistently demonstrate IGT, as determined using the oral glucose tolerance test.[26, 27, 28, 29]

Baseline plasma glucose is the most consistent predictor of progression to diabetes. Individuals who progress to diabetes tend to have rates of cardiovascular risk factors that are intermediate between persons with normal glucose tolerance and those with diabetes. They are at an increased risk of macrovascular complications (eg, coronary disease, gangrene, stroke). Progression to diabetes is not clearly associated with microvascular complications (eg, nephropathy, retinopathy, neuropathy). However, microvascular complications have been found in certain individuals with IGT.[30, 31]

Impaired fasting glucose is not associated with the same risk level as IGT, and the risk of cardiovascular disease is much lower in those with impaired fasting glucose.

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Patient Education

It is important to educate patients on the disease, including treatment, monitoring, complications, and primary and secondary preventive measures. In addition, family members should be educated on various related issues, including the management of hypoglycemia. For excellent patient education resources, visit eMedicineHealth's Diabetes Center. Also, see eMedicineHealth's patient education articles Diabetes Mellitus and Diabetic Eye Disease.

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Contributor Information and Disclosures
Author

Samuel T Olatunbosun, MD, FACP, FACE Endocrinology Service, SAMMC/59th Medical Wing and Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine

Samuel T Olatunbosun, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, Endocrine Society, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

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, Royal College of Physicians, and The Endocrine Society

Disclosure: Eli Lilly None Speaking and teaching; GlaxoSmithKline None Speaking and teaching; Merck None Speaking and teaching

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.

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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. American Diabetes Association. Standards of medical care in diabetes--2015: summary of revisions. Diabetes Care. 2015 Jan. 38 Suppl:S4. [Medline].

  2. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. 2005 Mar. 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, Roekaerts PM, Saris WH, Blaak EE. Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss. Obesity (Silver Spring). 2008 May. 16(5):1025-32. [Medline].

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

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

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

  9. Li CL, Chen SY, Lan C, Pan WH, Chou HC, Bai YB, et al. The effects of physical activity, body mass index (BMI) and waist circumference (WC) on glucose intolerance in older people: A nationwide study from Taiwan. Arch Gerontol Geriatr. 2010 Mar 3. [Medline].

  10. Ko GT, So WY, Tong P, Ma RC, Kong AP, Ozaki R, et al. Hypoadiponectinaemia enhances waist circumference as a predictor of glucose intolerance and clustering of risk factors in Chinese men. Diabetes Metab. 2010 Jun. 36(3):192-7. [Medline].

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

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

  13. Ahrén 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 Feb 21-27. 102(8):545-9. [Medline].

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

  15. 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. 2006 Jun. 29(6):1263-8. [Medline]. [Full Text].

  16. Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, 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. 1998 Apr. 21(4):518-24. [Medline]. [Full Text].

  17. 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 Jan. 16(1):157-77. [Medline].

  18. Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985. 727:1-113. [Medline].

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

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

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

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

  23. Tam WH, Ma RC, Yang X, Li AM, Ko GT, Kong AP, et al. Glucose intolerance and cardiometabolic risk in adolescents exposed to maternal gestational diabetes: a 15-year follow-up study. Diabetes Care. 2010 Jun. 33(6):1382-4. [Medline]. [Full Text].

  24. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC. Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med. 2010 Feb 11. 362(6):485-93. [Medline].

  25. Kakad R, Anwar A, Dyer P, Webber J, Dale J. Fasting plasma glucose is not sufficient to detect ongoing glucose intolerance after pregnancy complicated by gestational diabetes. Exp Clin Endocrinol Diabetes. 2010 Apr. 118(4):234-6. [Medline].

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

  27. Blake DR, Meigs JB, Muller DC, Najjar SS, Andres R, Nathan DM. 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. 2004 Aug. 53(8):2095-100. [Medline].

  28. Festa A, D'Agostino R Jr, Hanley AJ, Karter AJ, Saad MF, Haffner SM. Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. Diabetes. 2004 Jun. 53(6):1549-55. [Medline].

  29. 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. 1998 Aug. 41(2):147-8. [Medline].

  30. Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes. 2003 Dec. 52 (12):2867-73. [Medline].

  31. Grundy SM. Pre-diabetes, metabolic syndrome, and cardiovascular risk. J Am Coll Cardiol. 2012 Feb 14. 59 (7):635-43. [Medline].

  32. Faerch K, Vaag A, Holst JJ, Glümer C, Pedersen O, Borch-Johnsen K. 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. 2008 May. 51(5):853-61. [Medline].

  33. Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, Pratley R, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care. 2007 Mar. 30(3):753-9. [Medline].

  34. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May 8. 358 (19):1991-2002. [Medline].

  35. Committee on Practice Bulletins--Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013 Aug. 122 (2 Pt 1):406-16. [Medline].

  36. Bersoux S, Cook CB, Wu Q, et al. Hemoglobin a1c testing alone does not sufficiently identify patients with prediabetes. Am J Clin Pathol. 2011 May. 135(5):674-7. [Medline].

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

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

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

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

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

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

  43. van Raalte DH, van Genugten RE, Linssen MM, Ouwens DM, Diamant M. Glucagon-like peptide-1 receptor agonist treatment prevents glucocorticoid-induced glucose intolerance and islet-cell dysfunction in humans. Diabetes Care. 2011 Feb. 34(2):412-7. [Medline]. [Full Text].

  44. 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. 2005 Mar. 28(3):632-7. [Medline].

  45. Hollander P, Ratner R, Fineman M, Strobel S, Shen L, Maggs D, 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. 2003 Nov. 5(6):408-14. [Medline].

  46. Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, 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. 2004 Nov. 21(11):1204-12. [Medline].

  47. Riddle M, Frias J, Zhang B, Maier H, Brown C, Lutz K, et al. Pramlintide improved glycemic control and reduced weight in patients with type 2 diabetes using basal insulin. Diabetes Care. 2007 Nov. 30(11):2794-9. [Medline].

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

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

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

  51. 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. 2006 Jan-Feb. 12 Suppl 1:25-30. [Medline].

  52. Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, 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. 2007 Feb 10. 334(7588):299. [Medline]. [Full Text].

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

  54. Herman WH, Hoerger TJ, Brandle M, Hicks K, Sorensen S, Zhang P, et al. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Ann Intern Med. 2005 Mar 1. 142(5):323-32. [Medline]. [Full Text].

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

  56. Meneghini LF. Impact of bariatric surgery on type 2 diabetes. Cell Biochem Biophys. 2007. 48(2-3):97-102. [Medline].

  57. Hofsø D, Jenssen T, Bollerslev J, Ueland T, Godang K, Stumvoll M, et al. Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention. Eur J Endocrinol. 2011 Feb. 164(2):231-8. [Medline]. [Full Text].

  58. 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. 2008 Mar. 87(3):655-61. [Medline].

  59. 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. 2004 Sep 25. 148(39):1912-7. [Medline].

  60. UK Prospective Diabetes Study (UKPDS) Group. 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. 1998 Sep 12. 352(9131):854-65. [Medline].

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

  62. 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). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12. 352(9131):837-53. [Medline].

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

  64. Li CL, Pan CY, Lu JM, Zhu Y, Wang JH, Deng XX, et al. Effect of metformin on patients with impaired glucose tolerance. Diabet Med. 1999 Jun. 16(6):477-81. [Medline].

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

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

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

  68. Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011 May. 96(5):1301-10. [Medline].

  69. Standards of medical care in diabetes--2013. Diabetes Care. 2013 Jan. 36 Suppl 1:S11-66. [Medline]. [Full Text].

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

  71. Hanefeld M, Temelkova-Kurktschiev T, Schaper F, Henkel E, Siegert G, Koehler C. Impaired fasting glucose is not a risk factor for atherosclerosis. Diabet Med. 1999 Mar. 16(3):212-8. [Medline].

  72. Koska J, DelParigi A, de Courten B, Weyer C, Tataranni PA. Pancreatic polypeptide is involved in the regulation of body weight in pima Indian male subjects. Diabetes. 2004 Dec. 53(12):3091-6. [Medline].

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

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

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

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

  77. 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. 2004 Jun. 64(3):213-9. [Medline].

  78. 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. 1993 Sep 30. 329(14):977-86. [Medline].

 
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Etiologic types and stages of the major disorders of glucose tolerance.
 
 
 
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