Prediabetes

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Prediabetes
ICD-10 R73.0
ICD-9 790.29
MeSH D011236

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Overview

Prediabetes is the state in which blood glucose levels are above normal but have not reached that of diabetes. This state is also referred to as borderline diabetes, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG). These are associated with insulin resistance and are risk factors for the development of type 2 diabetes mellitus. In addition, obesity, family history of type 2 diabetes mellitus, and certain ethnic groups are also at high-risk. 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. [1] [2][3]

Diabetes mellitus (DM) is a group of metabolic diseases that are characterized by hyperglycemia 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 can be insidious, the diagnosis is often delayed. Effects of the disease can be macrovascular, as seen in the cardiovascular system/arthrosclerosis, or microvascular, as seen with retinopathy, nephropathy, and neuropathy. [4]

Epidemiology

About one third of Americans have prediabetes.[5][6]

Signs and symptoms

Prediabetes typically has no signs or symptoms. patients should monitor for signs and symptoms of type 2 diabetes mellitus. These include the following:

Genetics

As the human genome is further explored, it is likely that multiple genetic anomalies at different loci will be found that confer varying degrees of predisposition to type 2 diabetes. [8] Type 2 DM, which is the condition for which prediabetes is a precursor, has 90-100% concordance in twins; there is no HLA association.[9]

Pathophysiology

Normal glucose homeostasis is controlled by three interrelated processes. There is 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 islet cells. What triggers the production and release of insulin from the pancreas is the presence of glucose in the body. The main function of insulin is to increase the rate of transport of glucose into certain cells of the body, such as striated muscles, fibroblasts, and fat cells. It is also 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 by first 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 from a lack of pancreatic enzyme release or failure of target tissues to respond to the insulin present or both. [10]

Diagnosis

Prediabetes can be diagnosed in different ways. Each, however, must be confirmed with repeat testing on separate days. The diagnosis of IFG is done after an 8 hour fast; the plasma glucose level must be greater than 99 but less than 126. In order to diagnose IGT, the plasma glucose level must be greater than 139 but less than 200 two hours after an OGTT (oral glucose tolerance test), which is an oral load of 75 grams of glucose. A random glucose level over 140 at any time can result in the diagnosis of prediabetes.[11]

A meta-analysis of the accuracy of the fasting plasma glucose for current prediabetes found: [12]

A meta-analysis of the accuracy of the glycosylated hemoglobin for current prediabetes found: [12]

Screening

Prevention

The goals of prevention are to delay the onset of type 2 diabetes, preserving the function of the beta cells, and preventing or delaying the microvascular and cardiovascular complications. Obesity is an extremely important environmental influence, therefore, exercise, weight loss, and drug therapies have been studied. It has been found that lifestyle modification/intervention provides the greatest benefit in preventing the progression into type 2 diabetes. [13]

Treatment and Management

A systematic review of screening for diabetes for the U.S. Preventive Services Task Force found:

  • Screening for diabetes did not improve mortality rates after 10 years of follow-up, but treatment of IFG or IGT was associated with a moderate benefit in delaying progression to diabetes.[14]

A systematic review for the Community Preventive Services Task Force of lifestyle modifications to prevent diabetes in patients with prediabetes[15]:

  • Programs based on Diabetes Prevention Program study or the Finnish Diabetes Prevention Study which were more intensive and had more direct interaction than many other programs resulted in more weight loss and lower incidence of diabetes.

The Diabetes Prevention Program (DPP) randomized controlled trial, comparing intensive lifestyle intervention with masked metformin and placebo among patients at high risk for diabetes, showed the following relative risk reductions in incidence of diabetes compared to placebo:[16]

The "Let's Prevent Diabetes" Trial also found benefit from a lifestyle and eating educational program to prevent diabetes.[17]

Intensive weight loss and lifestyle intervention, if sustained, can substantially improve glucose tolerance and prevent progression from IGT to type 2 diabetes. In the Diabetes Prevention Program (DPP)[2] study, there was found to be 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.

Receiving a diagnosis of prediabetes may increase patient engagement with improving health behavior and healthy lifestyle.[18]

At long-term follow-up, behavior changes may persist at 10 years[19], and at 15-year follow-up study suggests that long-term lifestyle modification is superior to metformin, with a 27% reduced diabetes incidence with lifestyle intervention vs. 18% reduced diabetes incidence with metformin intervention[16].

Metformin can 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.[20] The ADA guidelines [3] recommend modest weight loss (5-10% body weight, moderate-intensity exercise (30 minutes daily), and smoking cessation.

Cure

There currently is no cure. Prevention and delay of the disease are key. There are studies being conducted, but no cure has yet to be found. However as per Ayurveda Diabetes can be cured with the help of Pranayam and Yogasanas.

Prognosis

The progression to type 2 diabetes mellitus is not inevitable for those with prediabetes. The progression into DM from prediabetes (IFG or IGT) is approximately 25% over three to five years [21]

Epidemiology

Studies conducted from 1988-1994 indicated that at that time, 33.8% of the US population 40-74 years of age had IFG, 15.4% had IGT, and 40.1% had prediabetes (IFG, IGT, or both). Eighteen million people (6.3% of the population) had type 2 diabetes in 2002.[22]

References

  1. "The Prevention or Delay of Type 2 Diabetes," ADA, Diabetes Care, 25: 742-749, 2002.
  2. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf
  3. Tominaga et al. "Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study," Diabetes Care 1999 Jun;22(6):920-4.
  4. Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.
  5. Menke A, Casagrande S, Geiss L, Cowie CC (2015). "Prevalence of and Trends in Diabetes Among Adults in the United States, 1988-2012.". JAMA. 314 (10): 1021–9. PMID 26348752. doi:10.1001/jama.2015.10029. 
  6. Cowie CC, Rust KF, Ford ES, Eberhardt MS, Byrd-Holt DD, Li C; et al. (2009). "Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006.". Diabetes Care. 32 (2): 287–94. PMC 2628695Freely accessible. PMID 19017771. doi:10.2337/dc08-1296. 
  7. Mayo Clinic Diabetes: "Prediabetes",http://www.mayoclinic.com/health/prediabetes/DS00624/DSECTION=2
  8. UpToDate: Classification of diabetes mellitis and genetic diabetic syndromes, Nov 14, 2007
  9. Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.
  10. Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.
  11. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf
  12. 12.0 12.1 Barry, Eleanor; Roberts, Samantha; Oke, Jason; Vijayaraghavan, Shanti; Normansell, Rebecca; Greenhalgh, Trisha (2017-01-04). "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. 356: –6538. ISSN 1756-1833. PMID 28052845. doi:10.1136/bmj.i6538. Retrieved 2017-01-05. 
  13. UptoDate: Prediction and prevention of type 2 diabetes mellitus; www.utdol.com/utd/content/topic.do?topicKey=diabetes.
  14. Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R (2015). "Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force.". Ann Intern Med. 162 (11): 765–76. PMID 25867111. doi:10.7326/M14-2221.  Review in: Ann Intern Med. 2015 Sep 15;163(6):JC2 Review in: Evid Based Med. 2015 Aug;20(4):136
  15. Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL (2015). "Combined Diet and Physical Activity Promotion Programs to Prevent Type 2 Diabetes Among Persons at Increased Risk: A Systematic Review for the Community Preventive Services Task Force.". Ann Intern Med. 163 (6): 437–51. PMID 26167912. doi:10.7326/M15-0452. 
  16. 16.0 16.1 Diabetes Prevention Program Research Group (2015). "Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study.". Lancet Diabetes Endocrinol. 3 (11): 866–75. PMC 4623946Freely accessible. PMID 26377054. doi:10.1016/S2213-8587(15)00291-0. 
  17. Gray LJ et a; (2016). Engagement, Retention, and Progression to Type 2 Diabetes: A Retrospective Analysis of the Cluster-Randomised "Let's Prevent Diabetes" Trial. Plos Medicine
  18. Gopalan A, Lorincz IS, Wirtalla C, Marcus SC, Long JA (2015). "Awareness of Prediabetes and Engagement in Diabetes Risk-Reducing Behaviors.". Am J Prev Med. 49 (4): 512–9. PMID 26091928. doi:10.1016/j.amepre.2015.03.007. 
  19. Rockette-Wagner B, Storti KL, Dabelea D, Edelstein S, Florez H, Franks PW; et al. (2016). "Activity and Sedentary Time 10 Years After a Successful Lifestyle Intervention: The Diabetes Prevention Program.". Am J Prev Med. PMID 27887769. doi:10.1016/j.amepre.2016.10.007. 
  20. UptoDate: Prediction and prevention of type 2 diabetes mellitus; www.utdol.com/utd/content/topic.do?topicKey=diabetes.
  21. Nathan et al. "Impaired fasting glucose and impaired glucose tolerance: implications for care," Diabetes Care. 2007 Mar;30(3):753-9.
  22. CDC: Diabetes. National Diabetes Fact Sheet; United States, 2003.
Cost Effectiveness of Prediabetes

| group5 = Clinical Trials Involving Prediabetes | list5 = Ongoing Trials on Prediabetes at Clinical Trials.govTrial results on PrediabetesClinical Trials on Prediabetes at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Prediabetes | list6 = US National Guidelines Clearinghouse on PrediabetesNICE Guidance on PrediabetesNHS PRODIGY GuidanceFDA on PrediabetesCDC on Prediabetes


| group7 = Textbook Information on Prediabetes | list7 = Books and Textbook Information on Prediabetes


| group8 = Pharmacology Resources on Prediabetes | list8 = AND (Dose)}} Dosing of PrediabetesAND (drug interactions)}} Drug interactions with PrediabetesAND (side effects)}} Side effects of PrediabetesAND (Allergy)}} Allergic reactions to PrediabetesAND (overdose)}} Overdose information on PrediabetesAND (carcinogenicity)}} Carcinogenicity information on PrediabetesAND (pregnancy)}} Prediabetes in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Prediabetes


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Prediabetes | list9 = AND (pharmacogenomics)}} Genetics of PrediabetesAND (pharmacogenomics)}} Pharmacogenomics of PrediabetesAND (proteomics)}} Proteomics of Prediabetes


| group10 = Newstories on Prediabetes | list10 = Prediabetes in the newsBe alerted to news on PrediabetesNews trends on Prediabetes</small>


| group11 = Commentary on Prediabetes | list11 = Blogs on Prediabetes

| group12 = Patient Resources on Prediabetes | list12 = Patient resources on PrediabetesDiscussion groups on PrediabetesPatient Handouts on PrediabetesDirections to Hospitals Treating PrediabetesRisk calculators and risk factors for Prediabetes


| group13 = Healthcare Provider Resources on Prediabetes | list13 = Symptoms of PrediabetesCauses & Risk Factors for PrediabetesDiagnostic studies for PrediabetesTreatment of Prediabetes

| group14 = Continuing Medical Education (CME) Programs on Prediabetes | list14 = CME Programs on Prediabetes

| group15 = International Resources on Prediabetes | list15 = Prediabetes en EspanolPrediabetes en Francais

| group16 = Business Resources on Prediabetes | list16 = Prediabetes in the MarketplacePatents on Prediabetes

| group17 = Informatics Resources on Prediabetes | list17 = List of terms related to Prediabetes


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