Prediabetes

Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms, but people with prediabetes often have obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes, as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes. Prediabetes can be diagnosed by measuring hemoglobin A1c, fasting glucose, or glucose tolerance test. Many people may be diagnosed through routine screening tests. The primary treatment approach includes lifestyle changes such as exercise and dietary adjustments. Some medications can be used to reduce the risks associated with prediabetes. There is a high rate of progression to type 2 diabetes but this does not develop for everyone with prediabetes. Prediabetes can be a reversible condition with lifestyle changes. For many people, prediabetes and diabetes are diagnosed through a routine screening at a check-up. The earlier prediabetes is diagnosed, the more likely an intervention will be successful.

Signs and symptoms Prediabetes typically has no distinct signs or symptoms except the sole sign of high blood sugar. People with prediabetes should monitor for signs and symptoms of type 2 diabetes such as increased thirst, increased urination, and feeling tired.

Causes The cause of prediabetes is multifactorial and is known to have contributions from lifestyle and genetic factors. Ultimately prediabetes occurs when control of insulin and blood glucose in the body becomes abnormal, also known as insulin resistance. Risk factors for developing prediabetes include being overweight or obese, physical inactivity, an unhealthy diet, a family history of diabetes, having a genetic predisposition to prediabetes or diabetes, older age, and women who have a history of gestational diabetes or of giving birth to high birth weight infants (greater than 9 pounds or 4.1 kg). The increasing rates of prediabetes and diabetes suggest that lifestyle and/or environmental factors contribute to prediabetes. It remains unclear which dietary components are causative and risk is likely influenced by genetic background. Increasing physical activity and following a healthy diet can reduce the risk of progressing to type 2 diabetes.

Pathophysiology 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. In individuals with prediabetes, a failure of pancreatic hormone release, failure of targeted tissues to respond to the insulin present or both leads to blood glucose rises to abnormally high levels.

Diagnosis Prediabetes can be diagnosed with three different types of blood tests:

Fasting blood sugar (glucose) level of: 110 to 125 mg/dL (6.1 mmol/L to 6.9 mmol/L) – WHO criteria 100 to 125 mg/dL (5.6 mmol/L to 6.9 mmol/L) – ADA criteria Glucose tolerance test: blood sugar level of 140 to 199 mg/dL (7.8 to 11.0 mM) 2 hours after ingesting a standardized 75 gram glucose solution (WHO and ADA criteria) Glycated hemoglobin (HbA1c) between 5.7 and 6.4 percent, i.e., 38.9 and 46.4 mmol/mol Levels above these limits would justify a diagnosis for diabetes.

Impaired fasting glucose

Impaired fasting glycemia or impaired fasting glucose (IFG) refers to a condition in which the fasting blood glucose 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. 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. Some patients with impaired fasting glucose also may be diagnosed with impaired glucose tolerance, but many have normal responses to a glucose tolerance test. Fasting glucose is helpful in identifying prediabetes when positive but has a risk of false negatives. 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) ADA criteria: fasting plasma glucose level from 5.6 mmol/L (100 mg/dL) to 6.9 mmol/L (125 mg/dL)

Impaired glucose tolerance Impaired glucose tolerance (IGT) is diagnosed with an oral glucose tolerance test. According to the criteria of the World Health Organization and the American Diabetes Association, impaired glucose tolerance is defined as:

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