Exploring Prediabetes: Seizing the Reversal Golden Window and Building a Healthier Community

I. Prediabetes Prevalence in the United States

Prediabetes is far more common than many people realize. Approximately 38% of U.S. adults have prediabetes (Figure 1) [1]. According to the Centers for Disease Control and Prevention (CDC)[2], the condition also affects 1 in 5 adolescents and 1 in 4 young adults in the United States.

Most people with prediabetes have no obvious symptoms and are unaware that they have it. Yet without early intervention, prediabetes can increase the risk of developing type 2 diabetes (T2D), cardiovascular disease, and stroke [3].

Early recognition of prediabetes provides an opportunity for timely intervention. Particularly among young people, taking action early may help delay the progression to T2D and, in some cases, reverse prediabetes.

Figure 1. Approximately 38%of U.S. adults have prediabetes, as reported in JAMA.

II. The Golden Window for Preventing T2D

Prediabetes does not progress to T2D overnight. The transition is driven by two major factors: insulin resistance and the gradual decline of pancreatic β-cell function [4,5]. Without intervention, β-cell function continues to deteriorate, reaching approximately 50% of normal by the time T2D is diagnosed (Figure 2) [4,6]. Studies suggest that this decline begins about 10–12 years before diagnosis and continues thereafter [7].

Unfortunately, most people are unaware that they have prediabetes. According to the CDC, more than 80% of individuals with prediabetes do not know they have the condition. Without intervention, many people with prediabetes may develop T2D within about 5 years [8].

Prediabetes often develops several years before the onset of T2D, providing a valuable golden window for intervention. Once substantial β-cell function has been lost, restoring normal glucose regulation becomes increasingly difficult.

Figure 2. The golden window for preventing T2D. Without intervention, pancreatic β-cell function declines progressively during the transition from prediabetes to T2D. At the time of diagnosis, β-cell function is approximately 50% of normal, as indicated by the red dashed line. The blue dashed line, derived from the UKPDS HOMA data, illustrates the progressive decline in β-cell function from the prediabetes stage through the diagnosis of T2D and beyond.

HOMA=Homeostasis Model Assessment; IGT=Impaired Glucose Tolerance.

III. Insulin Resistance Contributing to Prediabetes

Insulin resistance occurs when cells become less responsive to insulin, a hormone that helps glucose enter cells for energy [9]. As a result, the pancreas compensates by producing more insulin to maintain normal blood glucose levels. Although blood glucose may remain normal during this stage, the body is working harder to maintain this balance, placing stress on pancreatic β-cells (Figure 3).

Over time, β-cells may lose their ability to compensate for increasing insulin demands. As insulin production becomes insufficient, blood glucose levels begin to rise, leading to prediabetes and, if untreated, progression to T2D (Figure 3)[10].

Insulin resistance is commonly associated with unhealthy dietary patterns, including excess calories, rapidly absorbed sugars, refined carbohydrates, and sugary beverages [11], as well as physical inactivity. Improving diet quality and maintaining regular physical activity are essential strategies for improving insulin sensitivity and reducing the risk of progression [12].

Figure 3. Insulin resistance contributing to prediabetes. During insulin resistance, cells become less responsive to insulin, prompting the pancreas to produce more insulin to maintain normal blood glucose levels. Over time, pancreatic β-cells can no longer sustain this compensatory response, resulting in rising blood glucose levels and the development of prediabetes. Healthy lifestyle interventions can improve insulin sensitivity and reduce the risk of progression to T2D.

How Can You Tell If You May Have Insulin Resistance?

① Large Waist Circumference

Excess abdominal fat is strongly associated with insulin resistance and metabolic syndrome. In general, a healthy waist circumference is:

• Women: <80 cm (31.5 in)

• Most men: <94 cm (37 in) [13]

  
  

② Dark Skin Patches (Acanthosis Nigricans)

Dark, velvety patches of skin on the neck, armpits, knuckles, elbows, or knees may be a sign of significant insulin resistance [14].

③ Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

HOMA-IR is a widely used method for estimating insulin resistance using fasting glucose and fasting insulin:

HOMA-IR = (Fasting insulin × Fasting glucose) ÷ 22.5

Higher HOMA-IR values generally indicate greater insulin resistance. Interpretation should be based on laboratory reference ranges and individual clinical characteristics [15].

IV. Factors Associated with Prediabetes Among Young People in Schools

Approximately 1 in 4 U.S. young adults have prediabetes [2,16]. Common risk factors in school settings include sedentary behavior, physical inactivity, obesity, unhealthy dietary habits, challenging life transitions, and peer influence [17-18].

In addition to these well-recognized factors, chronic stress may also play an important role in the development of prediabetes among young people in school communities. Academic demands, examinations, financial concerns, work responsibilities, social pressures, and inadequate stress management may disrupt healthy eating, sleep, and physical activity, thereby increasing metabolic risk (Figure 4). Although more research is needed, our small-scale exploratory university survey identified early metabolic risk factors among young adults, including prediabetes, overweight/obesity and hypertension. These observations support the need for greater attention to metabolic health in school communities.

Figure 4. Common sources of chronic stress in school settings and their impact on students.

How Does Stress Contribute to Prediabetes?

Stress is a normal physiological response to challenging situations. However, when stress becomes chronic, the hypothalamic-pituitary-adrenal (HPA) axis is continuously activated, resulting in increased secretion of cortisol and other stress hormones [19]. Persistent elevation of these hormones can raise blood glucose levels and reduce insulin sensitivity, thereby contributing to insulin resistance and a greater risk of prediabetes (Figure 5) [20,21]. Consequently, clarifying the pathways through which chronic stress contributes to prediabetes is essential for developing effective early intervention strategies and mitigating the risk of clinical progression and its associated long-term complications[22].

Figure 5. A schematic diagram of the process of 'How Does Chronic Stress Affect Prediabetes?'

V. Why Prediabetes Matters Beyond Blood Glucose

Prediabetes is more than simply a state of mildly elevated blood glucose. Accumulating evidence indicates that it is associated with an increased risk of hypertension, T2D, cardiovascular disease, and several cancers, including colorectal, liver, pancreatic, stomach, breast, and ovarian cancers [23–27]. These conditions frequently coexist because they share common risk factors and underlying mechanisms, particularly insulin resistance, chronic inflammation, and metabolic dysfunction (Figure 6) [28].

Persistent hyperglycemia and hyperinsulinemia may promote oxidative stress, inflammation, and vascular injury, accelerating organ dysfunction and the development of multiple chronic diseases [28,29]. These findings emphasize that prediabetes is not merely a disorder of blood glucose regulation but a systemic metabolic condition with broad health implications.

Figure 6. Coexistence of prediabetes, type 2 diabetes, hypertension, and cancers: shared risk factors and underlying mechanisms.

VI. Prediabetes Diagnosis, Glucose Units Conversion, and HbA1c to Estimated Average Glucose

According to the American Diabetes Association (ADA), prediabetes can be diagnosed using any one of the following tests: fasting plasma glucose (FPG), a 2-hour oral glucose tolerance test (OGTT), or Glycated hemoglobin (HbA1c). The diagnostic ranges are shown below.

Diagnosis of Prediabetes (ADA) [30]

HbA1C

Fasting Plasma Glucose (FPG)

Oral Glucose Tolerance Test (OGTT)

Glucose Units Conversion ( mmol/L and mg/dL)[31]

Blood glucose is commonly reported in mg/dL (United States) or mmol/L (most other countries).

mmol/L = mg/dL ÷ 18

mg/dL = mmol/L × 18

HbA1c to Estimated Average Glucose (eAG) [32,33]   

(eAG) is calculated from your HbA1c result and reflects your average blood glucose level over the previous 2–3 months. It provides an easy way to understand what your HbA1c means in terms of average daily blood glucose. For example, an HbA1c of 5.6% corresponds to an eAG of approximately 114 mg/dL.

Use the ADA online calculator below to instantly convert your HbA1c to (eAG): https://professional.diabetes.org/glucose_calc.

VII.  Understanding Metabolism and Insulin

To better understand how prediabetes develops, it is helpful to first understand the basic concepts of metabolism and insulin.

1.Metabolism [34]

Metabolism refers to the chemical processes that convert food into energy and building blocks needed for growth, repair, and normal body function. It consists of two complementary processes: catabolism, which breaks down nutrients to release energy, and anabolism, which uses energy to build new molecules and tissues (Figure 7). Insulin is one of the key hormones regulating these metabolic processes.

The four major nutrient groups include:

• Carbohydrates

• Lipids and fatty acids

• Proteins and amino acids

• Nucleotides

Figure 7. Schematic diagram of catabolism and anabolism in cells and energy transfer to support life processes.

2. Insulin

The pancreas contains clusters of endocrine cells known as the islets of Langerhans, where β cells secrete insulin and α cells secrete glucagon (Figure 8) [34].

Insulin lowers blood glucose by promoting glucose uptake into muscle and adipose tissue for utilization or storage, whereas glucagon raises blood glucose by stimulating glucose release from the liver. Together, these hormones maintain normal blood glucose homeostasis (Figure 9). Disruption of this balance contributes to the development of prediabetes and T2D.[35].

Figure 9. Insulin and glucagon work together to maintain blood glucose homeostasis through balanced regulation.

Finally, we pay tribute to the pioneers who discovered insulin-Sir Frederick Banting and Charles Best-whose groundbreaking work has saved millions of lives worldwide.

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