Prediabetes
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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.  
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. 

# Epidemiology
About one third of Americans have prediabetes.

# 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

# 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.  Type 2 DM, which is the condition for which prediabetes is a precursor, has 90-100% concordance in twins; there is no HLA association.

# 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 tolerancein 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. 

# 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.
A meta-analysis of the accuracy of the fasting plasma glucose for current prediabetes found:
- Sensitivity = 25%
- Specificity = 94%
A meta-analysis of the accuracy of the glycosylated hemoglobin for current prediabetes found:
- Sensitivity = 50%
- Specificity = 80%

# Screening

## USPSTF Recommendations
This recommendation applies to adults aged 40 to 70 years who are seen in primary care settings and do not have obvious symptoms of diabetes. Persons who have a family history of diabetes, have a history of gestational diabetes or polycystic ovarian syndrome, or are members of certain racial/ethnic groups (that is, African Americans, American Indians or Alaskan Natives, Asian Americans, Hispanics or Latinos, or Native Hawaiians or Pacific Islanders) may be at increased risk for diabetes at a younger age or at a lower body mass index. Clinicians should consider screening earlier in persons with 1 or more of these characteristics. 

# Treatment and management
The goals 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.  Receiving a diagnosis of prediabetes may increase patient engagement with improving health behavior and healthy lifestyle.
The U.S. Preventive Services Task Force's systematic review of screening for diabetes 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.
The Community Preventive Services Task Force's systematic review of lifestyle modifications to prevent diabetes in patients with prediabetes:
- 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 "Let's Prevent Diabetes" Trial also found benefit from a lifestyle and eating educational program to prevent diabetes.
The ADA clinical practice guidelines  recommend modest weight loss (5-10% body weight, moderate-intensity exercise (30 minutes daily), and smoking cessation.

## Diabetes Prevention Program
The Diabetes Prevention Program (DPP) is a CDC recognized lifestyle intervention program designed for diagnosed prediabetic patients as an attempt to prevent or delay the progression of the disease to type 2 diabetes.
A meta-analysis by the Cochrane Collaboration found favorable effects on preventing cardiovascular outcomes of the DPP compared to alternatives including metformin. An previous meta-analysis by the Cochrane found benefit from counseling for diet and exercise.
In a 2015 randomized control trial comparing a YMCA Diabetes Prevention program to standard care, 12-month weight loss was 2.3 kilograms more for the DPP arm than for standard care participants. Additionally, persons attending 9 or more lessons had a 5.3-kilogram greater weight loss than did those with standard care alone. 
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:
- Lifestyle modification: 58%
- Metformin: 31%
- Lifestyle compared to Metformin: 39%
Intensive weight loss and lifestyle intervention, if sustained, can substantially improve glucose tolerance and prevent progression from IGT to type 2 diabetes, and has the potential to cut the incidence of diabetes in half. In the Diabetes Prevention Program (DPP) 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.
At long-term follow-up, behavior changes may persist at 10 years, 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. However, metformin may be superior for weight loss.
A structured decision aid may increase patients intentions to start lifestyle interventions.
Peer coaches may not add to the DPP.

## Metformin
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. However, metformin does not add to "intensive diet and exercise did not reduce or delay the risk of T2DM" according to a systematic review by the Cochrane Collaboration.

## Vitamin D
Vitamin D has been investigated but was not beneficial

# 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 

# 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.