Involves at least 25% of U.S. adults.

The term prediabetes refers to an intermediate state of glycemia between normal glucose regulation and diabetes, and is associated with increased risk of diabetes and cardiovascular disease.

Impaired glucose tolerance at a level of 140 through 199 mg perdL measured two hours after 75 g oral glucose load and indicated the patients with impaired glucose tolerance had a higher risk of developing diabetes then people without impaired”m glucose tolerance.

About 1 to 5% of people with impaired glucose tolerance, develop over diabetes annually, but many return to normal glucose regulation spontaneously.

Pathophysiology of pre-diabetes: patients with pre-diabetes have impaired fasting glucose and tend to have higher inappropriate endogenous glucose production because of hepatic insulin resistance, reduced hepatic glucose clearance, lower ability of glucose to stimulate its own uptake, and suppress its own production, patients with impaired fasting glucose have impaired beta cell function.

Impaired glucose tolerance is predominantly characterized by skeletal muscle resistance because it’s delayed glucose uptake, and by beta cell dysfunction,

People with prediabetes with impaired fasting glucose or impaired glucose tolerance exhibit varying degrees of insulin resistance, and beta cell dysfunction with near maximum insulin resistance, and beta cell function loss of 80% or greater in impaired glucose tolerance.

Longitudinal studies that observed adults with normal glucose regulation reported annual rates of incident pre-diabetes of 6.2% among predominantly White participants, 7.8% among people who were Indian, 11% among Black or White adults with parenteral history of type two diabetes.

Prevalence of pre-diabetes in recent studies what is greater than 38% in the overall population.

In a 2021 international study an estimate of the global impaired glucose tolerance prevalence was 10.2% corresponding to 541 million adults age 22-79 years.

During the past three decades, the prevalence of prediabetes has increased steadily among all races, ethnic, and age groups.

The resolution of pre-diabetes occurs in 33 to 59% of individuals within 1 to 5 years of follow up and 17 to 42% during 6 to 11 years of follow up, indicating the rates of resolution decrease with longer follow up.

Progression from normal glucose regulation to pre-diabetes is associated with increase body weight and insulin resistance combined with a decline in endogenous insulin secretion in response to glucose( beta cell dysfunction): Demonstrating that insulin resistance and beta cell failure evolve simultaneously rather than sequentially.

Postmortem investigations show approximately 40% relative decrease in pancreatic beta cell volume among individuals with pre-diabetes compared with those with normal fasting plasma glucose levels.


Of US adults, 88 million, more than 1 in 3 have prediabetes, and more than 8 in 10 of them don’t know they have it. 

Nearly 1 in five adolescents and about one in four young adults have pre-diabetes ( CDC).

In the US approximately 10% of people with pre diabetes  progress to having diabetes each year.

Affects 720 million people worldwide and is increasing.

Defined as impaired fasting glucose of 100-126 mg/dL after an overnight fast or a impaired glucose tolerance with a plasma glucose of 140-200 mg/dL after a 2 hour oral glucose tolerance test, or both.

A hemoglobin A1c level of 6.5% or higher is associated with an increase risk of retinopathy.

Patients with such a problem have an increased risk of developing type 2 diabetes, heart disease and stroke.

More than 80% of individuals with prediabetes are overweight or have a BMI of 25 or greater.

Lifestyle changes can prevent or delay the development of diabetes.

Patients with hemoglobin A1C results of 5.7-6.4% are conceded to be at high risk to develop diabetes, and therefore have prediabetes.

Individuals with prediabetes have an increased risk of developing type two diabetes, estimated at 5-10% annually and 70% in a lifetime.

The age of pre-diabetes influences the rate of progression to diabetes with individuals greater than 60 years appear to develop diabetes at a lower rate than middle-aged individuals with pre-diabetes.

Prediabetes is also a pro- inflammatory state, and the presence of inflammation in the prediabetic state predicts the onset of future diabetes.

Patients with prediabetes, have more cardiovascular disease risk than people without pre-diabetes, and have increased rates of cardiovascular events.

There is a higher mortality risk among patients with pre-diabetes, and is associated with a higher rate of hospitalization than normal glycemia.

Microvascular complications, including retinopathy, neuropathy, and nephropathy are frequent among prediabetics.

Up to to 7.9% of patients with prediabetes have retinopathy at baseline.

The proportion of individuals with pre-diabetes who had peripheral neuropathy is 7.5 to 16%.

The prevalence of chronic kidney disease among individuals with pre-diabetes is almost 10%.

Pre-diabetes is linked to higher frequency of impaired cognition and structural brain alterations compared with normal glucose regulation.

The USPSTF recommends that adults age 35-70 years who are overweight or obese be screened for pre-diabetesand type two diabetes and be offered or referred for a preventive pre-diabetic intervention.

Metformin is cost saving and the most effective agent for pre-diabetes among patients who are younger, have high levels obesity, and a history of gestational diabetes.
Among people with prediabetes, diabetes can be prevented with lifestyle modification, such as diet and exercise.
The beneficial effects of lifestyle modification a primarily mediated by weight loss.

Making lifestyle changes such as maintaining a healthy diet, engaging in regular physical activity, and losing weight can help prevent or delay the progression of prediabetes to type 2 diabetes.

Eating a healthy, balanced diet that is low in processed foods and added sugars can help keep blood sugar levels stable.

Engaging in regular physical activity can also help improve insulin sensitivity and lower blood sugar levels.

Additionally, losing weight can help reduce the risk of developing type 2 diabetes.

Randomized clinical trials have demonstrated that, compared with placebo, metformin reduces the incidence of diabetes among people with pre-diabetes.

Metformin is considered in patients with pre-diabetes and BMI 35 or greater, those younger than 60 years, women with a history of gestational diabetes, or those with higher fasting blood glucose levels (>110mg/cl) or higher hemoglobin A1c levels (>6).

Other agents used to prevent diabetes in patients with prediabetes include: thiazolidinedione, alpha glucosidase inhibitors, glucagon-like peptide1 analogues.

The long term effect of drugs for preventing diabetes is lower than intensive lifestyle modification.

After cessation of medications glycemia typically returns to original pre-diabetic range, whereas lifestyle modifications are more sustainable.



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