Diabetes mellitus is a chronic non-communicable disease with various complications and is one of the causes of disability, mortality, and high economic burden. Therefore, preventing diabetes mellitus is important. 

Prediabetes is a controversial condition regarding its diagnosis and intervention strategies. This condition is related to the risk of overdiagnosis and overtreatment. On the other hand, proper diagnosis and prediabetes intervention will reduce diabetes mellitus rates and complications.

An increase in the prediabetes population was recorded from 11.6% in 2003 to 35.3% in 2011. A total of 36.2% of adults in the United States and 50.1% in China belong to the prediabetes group.

Patients with prediabetic status often receive non-pharmacological and pharmacological interventions. This intervention can be useful in preventing DM and its complications. But, it is also considered to cause overdiagnosis, overtreatment, and expose patients to unnecessary drug side effects.


What is Prediabetes?

Prediabetes is a term used to describe sugar levels exceeding normal but not enough to be categorized as diabetes mellitus. Prediabetes includes impaired glucose tolerance and impaired fasting blood glucose. 



Prediabetes Diagnosis Criteria

According to the ADA, the criteria for prediabetes are:
  • Fasting blood sugar: 100-125 mg/dl
  • Blood sugar 2 hours postprandial  or oral glucose tolerance test: 140-199 mg/dl
  • HbA1c: 5.7% -6.4%

However, the threshold value of this diagnostic criterion may vary from country to country and association. Every doctor generally also has different preferences regarding the clinical guidelines used.



Prediabetes Related Diabetes Mellitus

Prediabetes and Risk of Diabetes Mellitus

Prediabetes (preDM) is one of the high risks for diabetes mellitus (DM). About 5% -10% of people with prediabetes per year become DM sufferers. According to data from the American Diabetes Association (ADA), about 70% of prediabetes people will become diabetic.

However, another study showed different figures. A meta-analysis showed that about 2/3 of patients with Impaired Fasting Glucose and more than half of Impaired Glucose Tolerance patients did not experience conversion to diabetes mellitus ten years. This difference may occur due to variations in the normal range for diagnosis.

However, prediabetes is not a risk factor for ensuring that someone will suffer from diabetes because this condition can also turn back to normoglycemic.


Prediabetes and Risk of  Diabetes Mellitus' Complications

Prediabetic patients also have the same risk of complications as diabetes mellitus. Prediabetic patients are at high risk for damage to organs, such as the eyes, kidneys, heart, and blood vessels. 
The most common prediabetes complications are:
  • neuropathy, 
  • nephropathy, even chronic kidney disease (CKD), 
  • diabetic retinopathy, 
  • and macrovascular disease.

The results of a study by Tabak et al. demonstrated that prediabetes could increase the risk of early diabetic nephropathy by 6% -10%. Pre-DM patients may also experience dysfunction of autonomic activism and erectile dysfunction. 

Neuropathy symptoms (such as hypoesthesia, hyperesthesia, and pain) are common in prediabetes, particularly with impaired glucose tolerance. Diabetic retinopathy was also found to occur in 8% of patients with pre-DM.



Overdiagnosis, Overtreatment, and Differences in Clinical Views

Labeling the patient with prediabetes is an overdiagnosing. When a patient is diagnosed with prediabetes, routine screening, doctor control, and certain drugs are necessary. In the era of health insurance, this can be quite a burden on medical costs, even though not all patients with prediabetes will experience diabetes mellitus.

The importance of the term "prediabetes" is increasingly being recognized. Nevertheless, doctors' views on prediabetes are still bivariate; most doctors have a positive view (58.4%) of prediabetes.

Doctors with less practical experience view and respond to prediabetes more positively. On the other hand, they tend to provide pharmacological management and do not provide education and non-pharmacological management, which are actually more needed in the prediabetes phase.

This significant difference in views is a separate obstacle for diabetes prevention efforts. Several studies suggest that the terminology of prediabetes is unnecessary. However, this stigma and perspective need to be examined further because the right pre diabetes intervention will prevent diabetes mellitus and its complications.

Doing early intervention in preDM patients provides more benefits than not. Pharmaceutical companies often use the label of prediabetes as a marketing tool to provide diabetes drugs. Doctors need to be aware that prediabetes management should focus on modifying lifestyle rather than administering antidiabetic drugs.

Existing studies show as many as 37% of people with prediabetes status will experience DM within four years if they do not get lifestyle modification interventions. Pharmacological interventions are also considered less effective for delaying or preventing type 2 diabetes in pre-DM patients.



Recommendations for the Prediabetes Treatment 

Existing studies show the benefit of early intervention in preventing or delaying diabetes mellitus, especially in high-risk groups.

Patients can be classified into high-risk groups based on the cumulation of the following criteria:
1. The patient has impaired glucose tolerance
2. The patient's fasting blood sugar is disturbed
3. HbA1c 5.7% -6.4%
4. Body mass index (BMI) ≥23 kg / m with risk factors, such as:
  • history of DM in the nuclear family (first-degree relative),
  • hypertension (≥140 / 90 mmHg) or in therapy,
  • lack of physical activity (
  • dyslipidemia (HDL <35 mg / dL and / or triglycerides> 250 mg / dL), (5) history of gestational diabetes,
  • women with polycystic ovary syndrome,
  • history of cardiovascular disease
5. Age> 45 years without risk factors


This risk assessment must be carried out carefully because it will determine the intervention carried out. Doctors must also consider the effectiveness of medical costs (cost-effectiveness) and compare the risks and benefits (risks and benefits) before determining the preventive measures.


a. Nonfarmacological Interventions

Non-pharmacological intervention with lifestyle modification is the main treatment that should be done and emphasized in prediabetic patients. Weight loss of 7% and physical activity of 150 minutes per week can reduce the risk of diabetes mellitus by 58%. and should be recommended in all high-risk patients.

Preventive measures that can be taken include:
  • Weight loss program: composition of a diet low in saturated fat, high in soluble fiber, choosing complex carbohydrates, and foods with a low glycemic index in the number of calories determined to achieve the ideal body weight target. Patients can undergo a certain diet program with a clinical nutrition specialist.
  • Physical exercise: physical exercise can be divided 3-4 times per week with a duration of 150 minutes/week with moderate aerobics (heart rate 50% -70% maximum) or 90 minutes/week with heavy aerobics (heart rate> 70% maximum).
  • Quit smoking
It is also important for high-risk patients to receive comprehensive education about diabetes mellitus and be referred for related prevention programs. Without lifestyle modification, 70% of preDM patients will experience type 2 diabetes within ten years.


b. Pharmacological Interventions

Pharmacological interventions are no more effective than education and lifestyle modification. Its effectiveness will also decrease after drug administration is stopped. The use of drugs for prediabetes is still not generally recommended for diabetes prevention by the FDA because the evidence is still minimal. Also, there are concerns that the label prediabetes is used.


c. Screening

Cardiovascular risk screening can be performed in high-risk groups. Routine DM screening for every three years can be done in high-risk groups with normal blood sugar. In patients included in the prediabetes group, the examination can be repeated every year.



Conclusion
Prediabetes is a condition of high blood sugar that needs special attention and plays an important role in preventing diabetes mellitus. Patients with prediabetes are at high risk of developing diabetes and its various complications.

Even so, keep in mind that prediabetes is not a disease where antidiabetic drugs are required. Patients with prediabetes can also return to normoglycemic by selecting the appropriate intervention.

The doctor's assessment of prediabetes's status must be carried out carefully because it will determine the intervention strategy. All patients with prediabetes need to be educated and motivated to modify diet and physical activity, whereas pharmacological intervention is only given to high-risk groups. The negative stigma against prediabetes status will be one of the obstacles preventing diabetes mellitus; therefore, doctors must carefully assess each patient's risk and intervene according to their needs.


References
1. American Diabetes Association. Diagnosing Diabetes and Learning About Prediabetes. ADA. 2015. http://www.diabetes.org/diabetes-basics/diagnosis/
2. American Diabetes Association. Prevention or delay of type 2 diabetes: Standards of Medical Care in Diabetes - 2018. Diabetes Care. 2018;41:S51
3. Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes. 2015;6:296.
4. Cefalu WT. “Prediabetes”: Are there problems with this label? No, we need a heightened awareness of this condition! Diabetes Care. 2016;39:1472–7.
5. International Diabetes Federation. IDF Diabetes Atlas 8th edition. 2017. IDF.  http://www.diabetesatlas.org
6. Mainous AG, Tanner RJ, Baker R, Zayas CE, Harle CA. Prevalence of prediabetes in England from 2003 to 2011: Population-based, cross-sectional study. BMJ Open. 2014;4:4–11.
7. Mainous AG, Tanner RJ, Scuderi CB, Porter M, Carek PJ. Prediabetes Screening and Treatment in Diabetes Prevention: The Impact of Physician Attitudes. J Am Board Fam Med. 2016;29:663–71.
8. McMurray JJV, Haffner SM, Califf RM, Holman RR. Prediabetes and the risk of diabetes. Lancet. 2012;380:1225–6.
9. Ryde L, Grant PJ, Anker SD, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2013;34: 3035–87.
10. Tabak AG, Herder C, Kivimäki M. Prediabetes : A high-risk state for developing diabetes. Lancet. 2012;379:2279–90.
11. Tuso P. Prediabetes and Lifestyle Modification: Time to Prevent a Preventable Disease. Perm J. 2014;18:88–93.
12. Twohig H, Hodges V, Mitchell C. Pre-diabetes: opportunity or overdiagnosis? Br J Gen Pract. 2018;172–3.
13. World Health Organization. Global Report On Diabetes. WHO. 2016.
14. Yudkin JS, Montori VM. The epidemic of pre-diabetes: The medicine and the politics. BMJ. 2014;349:18–20.
15. Yudkin JS. “Prediabetes”: Are there problems with this label? Yes, the label creates further problems! Diabetes Care. 2016;39:1468–71.