Open main menu


  (Redirected from Glucose tolerance)

Prediabetes is the precursor stage before diabetes mellitus in which not all of the symptoms required to diagnose diabetes are present, but blood sugar is abnormally high. This stage is often referred to as the "grey area".[1] It is not a disease; the American Diabetes Association says,[2] "Prediabetes should not be viewed as a clinical entity in its own right but rather as an increased risk for diabetes and cardiovascular disease (CVD). Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension."[2] It is thus a metabolic diathesis or syndrome, and it usually involves no symptoms and only high blood sugar as the sole sign.

SpecialtyEndocrinology Edit this on Wikidata

Impaired fasting blood sugar and impaired glucose tolerance are two forms of prediabetes that are similar in clinical definition (glucose levels too high for their context) but are physiologically distinct.[3] Insulin resistance, the insulin resistance syndrome (metabolic syndrome or syndrome X), and prediabetes are closely related to one another and have overlapping aspects.

Signs and symptomsEdit

Prediabetes typically has no distinct signs or symptoms except the sole sign of high blood sugar. Patients should monitor for signs and symptoms of type 2 diabetes mellitus such as increased thirst, increased urination, and feeling tired.[4]


Prediabetes develops when the body becomes insulin resistant or unable to use insulin.[5]

Some risk factors for diabetes are family history of diabetes, cardiovascular disease, increased triglyceride levels, low levels of HDL (good cholesterol), obesity, elevated blood pressure,[6] elevated fasting plasma glucose,[6][7] women who have had gestational diabetes, had high birth weight babies (greater than 9 lbs.), and/or have polycystic ovarian syndrome (PCOS)[8]

These are associated with insulin resistance and are risk factors for the development of type 2 diabetes mellitus. Those in this stratum (IGT or IFG) are at increased risk of cardiovascular disease. Of the two, impaired glucose tolerance better predicts cardiovascular disease and mortality.[9][10][11]

In a way, prediabetes is a misnomer since it is an early stage of diabetes. It now is known that the health complications associated with type 2 diabetes often occur before the medical diagnosis of diabetes is made.[12]


Type 2 DM, which is the condition for which prediabetes is a precursor, has 90–100% concordance in twins; there is no HLA association.[13] Genetics play a relatively small role, however, in the widespread occurrence of type 2 diabetes.[medical citation needed] This may be deduced logically from the huge increase in the occurrence of type 2 diabetes that has correlated with the significant change in western lifestyle and diet.[13] As the human genome is further explored, it is possible that multiple genetic anomalies at different loci will be found that confer varying degrees of predisposition to type 2 diabetes.[14]


Diabetes mellitus (DM) is a group of metabolic diseases that are characterised by hyperglycaemia and defects in insulin production in the pancreas and/or impaired tolerance to insulin effects. DM is a leading cause of morbidity and mortality. Because the disease may be insidious, the diagnosis often is delayed. Effects of the disease may affect larger blood vessels (e.g., atherosclerosis within the larger arteries of the cardiovascular system) or smaller blood vessels, as seen with damage to the retina of the eye, damage to the kidney, and damage to the nerves.[13]

Normal glucose homeostasis is controlled by three interrelated processes. These processes include gluconeogenesis (glucose production that occurs in the liver), uptake and utilization of glucose by the peripheral tissues of the body, and insulin secretion by the pancreatic beta islet cells. The presence of glucose in the bloodstream triggers the production and release of insulin from the pancreas' beta islet cells. The main function of insulin is to increase the rate of transport of glucose from the bloodstream into certain cells of the body, such as striated muscles, fibroblasts, and fat cells. It also is necessary for transport of amino acids, glycogen formation in the liver and skeletal muscles, triglyceride formation from glucose, nucleic acid synthesis, and protein synthesis.

Insulin enters cells first by binding to target insulin receptors. DM and some of those with prediabetes have impaired glucose tolerance—in these individuals, blood glucose rises to abnormally high levels. This may be due to a lack of pancreatic hormone release or failure of targeted tissues to respond to the insulin present or both.[13]


Usually, prediabetes is diagnosed with a blood test:[15]

  • Fasting blood sugar (glucose) level of:
    • 110 to 125 mg/dL (6.1 mM/L to 6.9 mM/L) – WHO criteria
    • 100 to 125 mg/dL (5.6 mM/L to 6.9 mM/L) – ADA criteria
  • Two hour glucose tolerance test after ingesting the standardized 75 Gm glucose solution the blood sugar level of 140 to 199 mg/dL (7.8 to 11.0 mM)[16]
  • Glycated haemoglobin between 5.7 and 6.4 percent[17]

Glycated hemoglobin is however, of questionable accuracy and while fasting glucose can indicate the diagnosis when positive if it is negative it is not very accurate.[18] A 2016 review found worse outcomes when blood sugar levels were over 100 mg/dL and glycated haemoglobin over 5.7%.[19]

Levels above these limits would justify a diagnosis for diabetes.


Impaired fasting glucoseEdit

Impaired fasting glycaemia or impaired fasting glucose (IFG) refers to a condition in which the fasting blood glucose or the 3-month average blood glucose (A1C) is elevated above what is considered normal levels but is not high enough to be classified as diabetes mellitus. It is considered a pre-diabetic state, associated with insulin resistance and increased risk of cardiovascular pathology, although of lesser risk than impaired glucose tolerance (IGT). IFG sometimes progresses to type 2 diabetes mellitus. There is a 50% risk over 10 years of progressing to overt diabetes. Many newly identified IFG patients progress to diabetes in less than three years.[20] IFG is also a risk factor for mortality.[21]

Fasting blood glucose levels are in a continuum within a given population, with higher fasting glucose levels corresponding to a higher risk for complications caused by the high glucose levels. Impaired fasting glucose is defined as a fasting glucose that is higher than the upper limit of normal, but not high enough to be classified as diabetes mellitus. Some patients with impaired fasting glucose also may be diagnosed with impaired glucose tolerance, but many have normal responses to a glucose tolerance test.

World Health Organization (WHO) criteria for impaired fasting glucose differs from the American Diabetes Association (ADA) criteria, because the normal range of glucose is defined differently by each. Fasting plasma glucose levels 100 mg/dL (5.5 mmol/L) and higher have been shown to increase complication rates significantly, however, WHO opted to keep its upper limit of normal at under 110 mg/dL for fear of causing too many people to be diagnosed as having impaired fasting glucose, whereas the ADA lowered the upper limit of normal to a fasting plasma glucose under 100 mg/dL.

  • WHO criteria: fasting plasma glucose level from 6.1 mmol/l (110 mg/dL) to 6.9 mmol/L (125 mg/dL)[22][23]
  • ADA criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL)

Impaired glucose toleranceEdit

Impaired glucose tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality.[21]

According to the criteria of the World Health Organization and the American Diabetes Association, impaired glucose tolerance is defined as:[22][24]

  • two-hour glucose levels of 140 to 199 mg per dL (7.8 to 11.0 mmol/l) on the 75-g oral glucose tolerance test. A patient is said to be under the condition of IGT when he/she has an intermediately raised glucose level after 2 hours, but less than the level that would qualify for type 2 diabetes mellitus. The fasting glucose may be either normal or mildly elevated.

From 10 to 15 percent of adults in the United States have impaired glucose tolerance or impaired fasting glucose.[25]


The risk of progression to diabetes and development of cardiovascular disease is greater than for impaired fasting glucose.[26]

Although some drugs can delay the onset of diabetes, lifestyle modifications play a greater role in the prevention of diabetes.[25][27] Patients identified as having an IGT may be able to prevent diabetes through a combination of increased exercise and reduction of body weight.[25] "Drug therapy can be considered when aggressive lifestyle interventions are unsuccessful."[25]

Subclinical diabetesEdit

Estimate of insulin resistance (IR) and insulin sensitivity (%S) according to the Homeostatic model assessment (HOMA). Patterns were modeled as a function of fasting plasma insulin and varying fasting plasma glucose. Calculated using HOMA Calculator. Adapted from [28]

Subclinical diabetes is a stage of hyperinsulinemia due to insulin resistance in normoglycemic individuals and, therefore, not diagnosed for hyperglycemic states characteristic of diabetes mellitus. It anticipates the prediabetes and diabetes stages characterized by hyperglycemia among other glucocentric biomarkers.[28] Insulin resistance can be diagnosed by measures of plasma insulin, both fasting or during a glucose tolerance test.[29][30] It has been endorsed by the American Diabetes Association in the Consensus Development Conference on Insulin Resistance,[31] where they state that "if the assay for fasting insulin was reliable, it would be useful to detect insulin resistance early (i.e., before or soon after the pubertal period, which itself causes insulin resistance) and before clinical disease appears".

The implications of a permanent hyperinsulinemic stage is the risk of comorbidities related to diabetes observed in subclinical diabetic individuals[32][33][34][28] including cardiovascular diseases.[35][36][37]


Fasting plasma glucose screening should begin at age 30–45 and be repeated at least every three years. Earlier and more frequent screening should be conducted in at-risk individuals. The risk factors for which are listed below:


The American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) have developed lifestyle intervention guidelines for preventing the onset of type 2 diabetes:

  • Healthy diet (a diet with limited saturated fats, no trans fats, refined sugars, and refined grains, as well as limited the intake of sodium and total calories)
  • Physical fitness (30–45 minutes of cardiovascular exercise per day, 3-5 days a week)
  • Weight loss by as little as 5–10 percent may have a significant impact on overall health


There is evidence that prediabetes is a curable disease state.[40] Intensive weight loss and lifestyle intervention, if sustained, may improve glucose tolerance substantially and prevent progression from IGT to type 2 diabetes. The Diabetes Prevention Program (DPP)[41] study found a 16% reduction in diabetes risk for every kilogram of weight loss. Reducing weight by 7% through a low-fat diet and performing 150 minutes of exercise a week is the goal. In observational studies, individuals following vegetarian diets are about half as likely to develop diabetes, compared with non-vegetarians.[42] The ADA guidelines recommend modest weight loss (5–10% body weight), moderate-intensity exercise (30 minutes daily), and smoking cessation.[43]

There are many anecdotal claims in the media and elsewhere that a high-fat, high-protein, low carbohydrates diet can reverse prediabetes, but more scientific evidence is needed to provide conclusive evidence for the efficacy of such diets.[44]

For patients with severe risk factors, prescription medication may be appropriate. This may be considered in patients for whom lifestyle therapy has failed, or is not sustainable, and who are at high-risk for developing type 2 diabetes.[45] Metformin[46] and acarbose help prevent the development of frank diabetes, and also have a good safety profile. Evidence also supports thiazolidinediones but there are safety concerns, and data on newer agents such as GLP-1 receptor agonists, DPP4 inhibitors or meglitinides are lacking.[47]


The progression to type 2 diabetes mellitus is not inevitable for those with prediabetes. The progression into diabetes mellitus from prediabetes is approximately 25% over three to five years.[48]


Studies conducted from 1988–1994 indicated that of the total population of US in the age group 40–74 years, 34% had IFG, 15% had IGT, and 40% had prediabetes (IFG, IGT, or both). Eighteen million people (6% of the population) had type 2 diabetes in 2002.[49]

The incidence of diabetes is growing. In 2014, 29.1 million people or 9% of the US population had diabetes.[50] In 2011–2012, the prevalence of diabetes in the U.S. using hemoglobin A1C, fasting plasma glucose or the two-hour plasma glucose definition was 14% for total diabetes, 9% for diagnosed diabetes, 5% for undiagnosed diabetes and 38% for prediabetes.[51]

See alsoEdit


  1. ^ "Prediabetes". Healthcureplus.
  2. ^ a b American Diabetes Association (January 2017). "2. Classification and diagnosis of diabetes". Diabetes Care. 40 (Suppl 1): S11–S24. doi:10.2337/dc17-S005. PMID 27979889.
  3. ^ Hanefeld M, Koehler C, Fuecker K, Henkel E, Schaper F, Temelkova-Kurktschiev T (March 2003). "Impaired Glucose Tolerance for Atherosclerosis and Diabetes study: Insulin Secretion and Insulin Sensitivity Pattern Is Different in Isolated Impaired Glucose Tolerance and Impaired Fasting Glucose". Diabetes Care. 26 (3): 868–874. doi:10.2337/diacare.26.3.868. PMID 12610051.
  4. ^ "Diabetes: 'Prediabetes'". Mayo Clinic. Retrieved January 27, 2009.
  5. ^ "Prediabetes Causes".
  6. ^ a b "Information on Pre-diabetes". Retrieved 2015-12-21.
  7. ^ "What is Pre-diabetes?". Equalibras.
  8. ^ "Power of Prevention". American College of Endocrinology. May 2009.
  9. ^ American Diabetes Association National Institute Of Diabetes, Digestive Kidney Diseases (2002). "The Prevention or Delay of Type 2 Diabetes". Diabetes Care. ADA. 25 (4): 742–49. doi:10.2337/diacare.25.4.742. PMID 11919135.
  10. ^ National Diabetes Fact Sheet (PDF). CDC.
  11. ^ Tominaga; et al. (Jun 1999). "Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study". Diabetes Care. 22 (6): 920–24. doi:10.2337/diacare.22.6.920. PMID 10372242.
  12. ^ "Prediabetes". WebMD. Retrieved January 27, 2009.
  13. ^ a b c d Cotran; Kumar; Collins (1999). Robbins Pathologic Basis of Disease (Saunders Sixth ed.). pp. 913–26.
  14. ^ UpToDate: Classification of diabetes mellitis and genetic diabetic syndromes (November 14, 2007)
  15. ^ "Prediabetes or Borderline Diabetes".
  16. ^ Jellinger, Paul S. (May 2009). "What You Need to Know about Prediabetes". Power of Prevention. American College of Endocrinology. 1 (2).
  17. ^ "New Guidelines Urge A1C Test for Diabetes Diagnosis". HealthDay. December 29, 2009. Archived from the original on March 25, 2010. Retrieved 2010-01-02.
  18. ^ Barry, E; Roberts, S; Oke, J; Vijayaraghavan, S; Normansell, R; Greenhalgh, T (4 January 2017). "Efficacy and effectiveness of screen and treat policies in prevention of type 2 diabetes: systematic review and meta-analysis of screening tests and interventions". BMJ (Clinical Research Ed.). 356: i6538. doi:10.1136/bmj.i6538. PMID 28052845.
  19. ^ Huang, Yuli; Cai, Xiaoyan; Mai, Weiyi; Li, Meijun; Hu, Yunzhao (23 November 2016). "Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis". BMJ. 355: i5953. doi:10.1136/bmj.i5953. PMC 5121106. PMID 27881363.
  20. ^ Nichols GA, Hillier TA, Brown JB (2007). "Progression From Newly Acquired Impaired Fasting Glusose to Type 2 Diabetes". Diabetes Care. 30 (2): 228–33. doi:10.2337/dc06-1392. PMC 1851903. PMID 17259486.
  21. ^ a b Barr EL, Zimmet PZ, Welborn TA, et al. (2007). "Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab)". Circulation. 116 (2): 151–57. doi:10.1161/CIRCULATIONAHA.106.685628. PMID 17576864.
  22. ^ a b World Health Organization. "Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus". Retrieved 2007-05-29.
  23. ^ American Diabetes Association (2005). "Diagnosis and classification of diabetes mellitus". Diabetes Care. 28 Suppl 1: S37–42. doi:10.2337/diacare.28.suppl_1.s37. PMC 3632174. PMID 15618111.
  24. ^ "Impaired Glucose Tolerance (IGT)". Retrieved 17 April 2018.
  25. ^ a b c d Shobha S. Rao; Phillip Disraeli; Tamara McGregor (15 April 2004). "Impaired Glucose Tolerance and Impaired Fasting Glucose". American Family Physician. 69 (8): 1961.
  26. ^ Oxford Handbook of Clinical Medicine, 7th Ed., Longmore, Wilkinson, Turmezei and Cheung. Oxford University Press 2007.
  27. ^ Raina Elley C, Kenealy T (December 2008). "Lifestyle interventions reduced the long-term risk of diabetes in adults with impaired glucose tolerance". Evid Based Med. 13 (6): 173. doi:10.1136/ebm.13.6.173. PMID 19043031.
  28. ^ a b c Lima, Luis Mauricio TR (2017). "Subclinical Diabetes" (PDF). An. Acad. Bras. Ciênc. 89 (1): 591–614. doi:10.1590/0001-3765201720160394. PMID 28492735.
  29. ^ Kraft, JR (1975). "Detection of Diabetes Mellitus In Situ (Occult Diabetes)". Laboratory Medicine. 6 (2): 10–22. doi:10.1093/labmed/6.2.10.
  30. ^ Reaven, GM; Lerner, RL; Stern, MP; Farguhar, JW (1967). "Role of insulin in endogenous hypertriglyceridemia" (PDF). The Journal of Clinical Investigation. 46 (11): 1756–67. doi:10.1172/JCI105666. PMC 292926. PMID 6061748.
  31. ^ Association, American Diabetes (1998). "Consensus Development Conference on Insulin Resistance: 5–6 November 1997". Diabetes Care. 21 (2): 310–14. doi:10.2337/diacare.21.2.310. PMID 9540000.
  32. ^ Keebler ME & McGuire DK 2003 Subclinical diabetes mellitus: is it really “sub-clinical”? American Heart Journal 146 210–12. doi:10.1016/S0002-8703(03)00236-9
  33. ^ Kulkarni RN 2012 "Identifying Biomarkers of Subclinical Diabetes". Diabetes 61 1925–26. doi:10.2337/db12-0599
  34. ^ Lima LMTR 2017 "Prediabetes definitions and clinical outcomes". The Lancet Diabetes & Endocrinology 5 92–93. doi:10.1016/S2213-8587(17)30011-6
  35. ^ Hanley AJG, Williams K, Stern MP & Haffner SM 2002 "Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care 25 1177–84.
  36. ^ Valenti V, Hartaigh B ó, Cho I, Schulman-Marcus J, Gransar H, Heo R, Truong QA, Shaw LJ, Knapper J, Kelkar AA et al. 2016 Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality A 15-Year Follow-Up Study of 9715 Patients. Circulation: Cardiovascular Imaging 9 e003528. doi:10.1161/CIRCIMAGING.115.003528
  37. ^ DECODE Study Group, European Diabetes Epidemiology Group 2003 "Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases?" Diabetes Care 26 688–696.
  38. ^ "ADA: Standards of Medical Care in Diabetes", Diabetes Care 27: Supp 1.515, 2004.
  39. ^ "Diabetes Guidelines Taskforce: AACE Guidelines for the Management of DM", Endocrin Pract 1995, 1.149
  40. ^ Eldin, W. Shehab; Emara, M.; Shoker, A. (2008-04-01). "Prediabetes: a must to recognise disease state". International Journal of Clinical Practice. 62 (4): 642–48. doi:10.1111/j.1742-1241.2008.01705.x. ISSN 1742-1241. PMID 18266711.
  41. ^ "Diabetes Prevention Program (DPP)".
  42. ^ Barnard, Neal D.; Katcher, Heather I.; Jenkins, David J. A.; Cohen, Joshua; Turner-McGrievy, Gabrielle (2009-05-01). "Vegetarian and vegan diets in type 2 diabetes management". Nutrition Reviews. 67 (5): 255–63. doi:10.1111/j.1753-4887.2009.00198.x. ISSN 1753-4887. PMID 19386029.
  43. ^ American Diabetes Association. "How to Prevent or Delay Diabetes". Archived from the original on 2009-08-22.
  44. ^ Taubes, Gary (27 December 2017). "Minimal carbs, lots of fat, incredible dieting results – but not enough science". Retrieved 2018-03-24.
  45. ^ UptoDate: Prediction and prevention of type 2 diabetes mellitus;
  46. ^ Lilly M, Godwin M (Apr 2009). "Treating prediabetes with metformin: systematic review and meta-analysis". Canadian Family Physician. 55 (4): 363–69.
  47. ^ "American College of Endocrinology Consensus Statement on the diagnosis and management of pre-diabetes in the continuum of hyperglycemia – When do the risks of diabetes begin?" (PDF). American College of Endocrinology Task Force on Pre-Diabetes. Retrieved 2008-07-24.
  48. ^ Nathan; et al. (Mar 2007). "Impaired fasting glucose and impaired glucose tolerance: implications for care". Diabetes Care. 30 (3): 753–39. doi:10.2337/dc07-9920. PMID 17327355.
  49. ^ CDC: Diabetes. National Diabetes Fact Sheet; United States, 2003.
  50. ^ Centers for Disease Control and Prevention (2014). "National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States, 2014". Atlanta, GA: U.S. Department of Health and Human Services. Archived from the original on 2016-12-02.
  51. ^ Menke, Andy; Casagrande, Sarah; Geiss, Linda; Cowie, Catherine C. (2015). "Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012". JAMA. 314 (10): 1021–9. doi:10.1001/jama.2015.10029. PMID 26348752.

Further readingEdit

External linksEdit