Prediabetes

Infobox_Disease
Name = Prediabetes


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ICD10 = ICD10|R|73|0|r|70
ICD9 = ICD9|790.29
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OMIM =
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MeshID = D011236

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. ["The Prevention or Delay of Type 2 Diabetes," ADA, "Diabetes Care", 25: 742-749, 2002.] [ [http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf National Diabetes Fact Sheet ] ] [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. ]

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 , 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. [Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.]

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:

*Constant hunger
*Unexplained weight loss
*Weight gain
*Flu-like symptoms, including weakness and fatigue
*Blurred vision
*Slow healing of cuts or bruises
*Tingling or loss of feeling in hands or feet
*Recurring gum or skin infections
*Recurring vaginal or bladder infections [Mayo Clinic Diabetes: "Prediabetes",http://www.mayoclinic.com/health/prediabetes/DS00624/DSECTION=2]

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. [UpToDate: Classification of diabetes mellitis and genetic diabetic syndromes, Nov 14, 2007] Type 2 DM, which is the condition for which prediabetes is a precursor, has 90-100% concordance in twins; there is no HLA association. [Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.]

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 hormone release or failure of target tissues to respond to the insulin present or both. [Cotran, Kumar, Collins; Robbins Pathologic Basis of Disease, Saunders Sixth Edition, 1999; 913-926.]

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. [ [http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf National Diabetes Fact Sheet ] ]

Screening

Fasting plasma glucose screening should begin at age at age 30-45 and 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:

*Family history (parent or sibling)
*Dyslipidemia (Triglycerides >200 or HDL < 35)
*Overweight or obese (Body Mass Index >25)
*History of gestational diabetes or infant born with birth weight greater than convert|9|lb|lk=on|abbr=on
*High risk ethnic group
*Hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg)
*Prior fasting blood glucose > 99
*Known vascular disease
*Markers of insulin resistance (PCOS, acanthosis nigricans) ["ADA: Standards of Medical Care in Diabetes," "Diabetes Care" 27: Supp 1.515, 2004.] ["Diabetes Guidelines Taskforce: AACE Guidelines for the Management of DM," "Endocrin Pract" 1995, 1.149]

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. [UptoDate: Prediction and prevention of type 2 diabetes mellitus; www.utdol.com/utd/content/topic.do?topicKey=diabetes.]

Treatment and Management

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) [http://diabetes.niddk.nih.gov/dm/pubs/preventionprogram/] 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. The ADA guidelines [https://www.diabetes.org/diabetes-prevention/how-to-prevent-diabetes.jsp] recommend modest weight loss (5-10% body weight, moderate-intensity exercise (30 minutes daily), and smoking cessation.

The use of medication is also an option that has been studied. This 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. [UptoDate: Prediction and prevention of type 2 diabetes mellitus; www.utdol.com/utd/content/topic.do?topicKey=diabetes.] Metformin 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.cite web |url=http://www.aace.com/meetings/consensus/hyperglycemia/hyperglycemia.pdf |title=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? |format=PDF |work=American College of Endocrinology Task Force on Pre-Diabetes |accessdate=2008-07-24]

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 [Nathan et al. "Impaired fasting glucose and impaired glucose tolerance: implications for care," "Diabetes Care". 2007 Mar;30(3):753-9.]

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. [CDC: Diabetes. National Diabetes Fact Sheet; United States, 2003.]

References