A Functional Medicine Approach to Prediabetes

Approximately 98 million American adults have prediabetes, but more than 80% don't know they have it. Prediabetes is a precursor to type 2 diabetes and puts individuals at an increased risk of heart disease, stroke, and cognitive decline. The good news is that modifiable factors largely influence prediabetes, so early identification and intervention significantly improve the chances of reversing this disease. This article will discuss a functional medicine approach to diabetes.

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What Is Prediabetes?

Prediabetes is a metabolic condition characterized by elevated blood glucose levels that are higher than normal but not yet at the threshold for a diabetes diagnosis. It serves as a crucial warning sign, indicating an increased risk of developing type 2 diabetes and cardiovascular diseases. This intermediary stage allows for proactive intervention to prevent or delay the progression to full-blown type 2 diabetes. 

In prediabetes, the body's insulin sensitivity is compromised, meaning that cells do not respond efficiently to insulin, leading to inadequate glucose uptake. Contributing factors to prediabetes include genetic predisposition, sedentary lifestyle, unhealthy dietary patterns, and excess body weight, particularly around the abdomen. 

Prediabetes is diagnosed through various laboratory tests that assess blood glucose levels. The commonly utilized criteria include measurements of fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1c) levels. According to the American Diabetes Association (ADA), the diagnostic thresholds for prediabetes are defined as follows:

1. FPG: A fasting blood glucose level between 100 and 125 mg/dL indicates impaired fasting glucose (IFG). Fasting is defined as no caloric intake for at least 8 hours.
2. OGTT: An OGTT measures blood glucose levels two hours after ingesting a standardized glucose solution. A result between 140 and 199 mg/dL signifies impaired glucose tolerance (IGT).
3. HbA1c: This test reflects average blood glucose levels over the past 2-3 months. An HbA1c level of 5.7% to 6.4% indicates prediabetes. The percentage corresponds to the amount of hemoglobin that is glycated, or bound to glucose.

The Functional Medicine Perspective on Prediabetes

From a functional medicine perspective, prediabetes is viewed as a manifestation of broader metabolic dysregulation rooted in a complex interplay of factors. Functional medicine aims to identify and address the underlying causes and systemic imbalances contributing to the development of prediabetes, providing a more comprehensive and personalized approach to management.

One key focus of functional medicine is recognizing the intricate connections between various bodily systems. Prediabetes is often associated with systemic inflammation, insulin resistance, and hormonal imbalances. Chronic inflammation, triggered by factors such as poor diet, sedentary lifestyle, environmental toxins, and gut dysbiosis, can disrupt the delicate balance of metabolic pathways, impairing insulin signaling and promoting insulin resistance. Prediabetics often meet the criteria for metabolic syndrome, a cluster of factors that carry a significant risk for cardiovascular disease and type 2 diabetes. These factors include increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated blood sugar. 

Insulin resistance is closely tied to the development of prediabetes, serving as a crucial link in the progression from normal glucose metabolism to impaired glucose regulation. The hormone insulin, produced by the pancreas, plays a central role in regulating blood glucose levels by facilitating glucose uptake into cells, particularly in the liver, muscle, and adipose tissue. In individuals with insulin resistance, cells become less responsive to the effects of insulin. This prompts the pancreas to produce more insulin to compensate for the reduced effectiveness and maintain normal blood glucose levels. This compensatory mechanism is an early response to insulin resistance. As insulin resistance progresses, the compensatory increase in insulin secretion may eventually become insufficient to overcome resistance, resulting in elevated blood glucose levels and the diagnosis of prediabetes. 

Several mechanisms contribute to the development of insulin resistance. Excess adipose tissue, especially abdominal or visceral fat, is strongly associated with insulin resistance as it releases substances like adipokines and free fatty acids, which can interfere with insulin signaling. Chronic low-grade inflammation, often associated with conditions like obesity, disrupts insulin receptor function, contributing to insulin resistance. Genetic factors also play a role in influencing insulin receptor function and other components of the insulin signaling pathway. However, environmental factors, particularly lifestyle choices such as a sedentary lifestyle and diets high in refined sugars, significantly contribute to insulin resistance. 

Moreover, functional medicine recognizes the role of hormonal imbalances, particularly those involving cortisol, thyroid hormones, and sex hormones, in contributing to prediabetes. Stress, inadequate sleep, and other lifestyle factors can disrupt the endocrine system, influencing glucose regulation and exacerbating metabolic dysfunction.

Nutritional imbalances are also integral to the functional medicine perspective on prediabetes. A diet rich in processed foods, refined sugars, and lacking essential nutrients can contribute to oxidative stress, impair mitochondrial function, and compromise overall metabolic health. Functional medicine interventions emphasize personalized nutrition plans, focusing on whole, nutrient-dense foods to address deficiencies and support optimal metabolic function.

Functional Medicine Lab Tests for Prediabetes

Functional medicine employs a comprehensive array of lab tests and diagnostics to assess prediabetes and general metabolic health, providing a more nuanced understanding of the individual's metabolic status and allowing for targeted interventions. The following outlines specific functional medicine lab tests used in the assessment of prediabetes:

Blood Sugar

As discussed above, prediabetes is diagnosed based on various measurements of blood sugar and glycemic control. HbA1c, which can be ordered through Access Med Labs, measures the average blood glucose levels over the last 2-3 months by assessing the percentage of glycated hemoglobin in red blood cells. HbA1c is a standard marker of diabetes used in conventional medicine, and functional medicine practitioners leverage it to gauge long-term glycemic control.  

A fasting blood glucose test, also available through Access Med Labs, provides insight into immediate glycemic status. Functional medicine doctors often utilize this as a quick point-of-care test and consider it alongside other markers for a comprehensive evaluation of metabolic function. 

A two-hour OGTT is one of the most sensitive measures of early glucose dysregulation. The test is abnormal if the patient's blood sugar is greater than 140 mg/dL two hours after consuming a glucose-containing drink. Elevated 2-hour glucose is correlated with an increased risk of all-cause mortality, independent of fasting glucose and HbA1c.

Hormones

Even with normal fasting glucose, increased fasting insulin levels correspond to insulin resistance. While standard reference ranges are very broad, generally between 2.6-24.9 μU/mL, functional medicine doctors agree that maintaining fasting insulin under 10 μU/mL reduces the risk of metabolic syndrome and type 2 diabetes.  

The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score is a validated assessment of insulin resistance. It uses a mathematical model that considers fasting insulin and glucose levels to produce a single score to indicate insulin resistance. Based on a 2021 NHANES analysis, 40% of US adults aged 18-44 are insulin-resistant based on HOMA-IR measurements. 

The HOMA-IR w/ Beta Cell Function test by BostonHeart Diagnostics is a comprehensive panel that measures fasting glucose, fasting insulin, and HOMA-IR to assess insulin sensitivity and pancreatic function. 

Because other hormones can influence glucose metabolism, functional medicine doctors may also order other hormonal panels to measure sex, stress, and thyroid hormones. These may include the DUTCH Complete by Precision Analytical and the Thyroid Health Panel by Ayumetrix.  

Metabolomic Profile

The Metabolomic Profile by Doctor's Data assesses metabolic syndrome risk by measuring multiple markers of fat stores, glucose balance, and inflammation. Biomarkers included in this panel include:

• 1,5-Anyhdroglyucitol (GlycoMark) indicates poor glucose control and frequent hyperglycemic events. Postprandial hyperglycemia is associated with cardiovascular disease and increased risk of vascular complications in diabetic patients (19).  
• HbA1c
• Insulin 
• Leptin is a hormone produced by fat cells to signal satiety. High levels of leptin have pro-inflammatory effects and are associated with increased adiposity. 
• Adiponectin improves insulin sensitivity and stimulates peripheral glucose uptake by cells. Meta-analyses have suggested that higher adiponectin levels are associated with a lower risk of diabetes. (31) 
• The leptin/adiponectin (L/A) ratio is a good indicator of dysfunctional adipose tissue and an estimator of cardiometabolic risk. 
• Cystatin C, creatinine, and eGFR are measured as kidney health and function markers. Chronic hyperglycemia triggers vascular inflammation, promoting the progression of kidney disease; monitoring kidney function is, therefore, an important aspect of prediabetes and diabetes management. 

Lipid Profile

Functional medicine providers consider lipid markers in the context of metabolic health. Dyslipidemia can be indicative of underlying metabolic imbalances contributing to prediabetes and contribute to cardiovascular disease risk. The Comprehensive Lipid Panel by BostonHeart Diagnostics measures 15 lipid markers to analyze a patient's risk of cardiovascular disease.

Organic Acid Test (OAT)

An OAT, commonly ordered through Mosaic Diagnostics,  is a diagnostic tool that examines metabolites in urine to gain insights into various metabolic processes within the body. This comprehensive test provides a snapshot of metabolic function, nutrient status, and microbial activity in the gastrointestinal tract. For individuals dealing with insulin resistance or prediabetes, the OAT offers several advantages. Firstly, it provides a closer look at mitochondrial function, assessing specific organic acids related to energy metabolism. The test also evaluates nutrient status, including B vitamins and antioxidants, which are crucial for metabolic processes. Additionally, it assesses the gut microbiome by identifying specific organic acids indicative of microbial overgrowth or imbalances, offering information on gut health. The OAT also measures markers related to oxidative stress and inflammation, factors associated with insulin resistance. (12) 

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Nutritional Strategies in Managing Prediabetes

Nutritional strategies play a pivotal role in preventing and managing prediabetes, with various diets showing promise in the literature for improving metabolic function and reducing the risk of progression to diabetes. 

Low-glycemic diets focus on consuming foods that have a minimal impact on blood sugar levels. These diets emphasize whole, unprocessed foods, such as non-starchy vegetables, legumes, and whole grains, while limiting refined carbohydrates and sugars. The glycemic index (GI) measures how quickly a food raises blood sugar levels, and low-GI foods are associated with improved insulin sensitivity. Several studies suggest that adherence to a low-glycemic diet may contribute to better glycemic control and reduced risk of developing type 2 diabetes. (13) 

The Mediterranean diet, characterized by high consumption of fruits, vegetables, whole grains, lean proteins, and healthy fats like olive oil, positively affects metabolic health. Studies indicate that the Mediterranean diet is associated with improved insulin sensitivity, lower fasting glucose levels, and a reduced risk of type 2 diabetes. The diet's emphasis on anti-inflammatory foods and its rich polyphenol content contribute to its metabolic benefits. (13)

Anti-inflammatory diets, often overlapping with Mediterranean diets, prioritize foods with anti-inflammatory properties. This includes omega-3 fatty acids from fish, nuts, seeds, and olive oil, as well as antioxidants found in fruits and vegetables. Research suggests that anti-inflammatory diets may positively impact insulin sensitivity and reduce inflammatory markers, protecting against prediabetes and metabolic dysfunction. (23) 

Lifestyle Modifications for Prediabetes

Lifestyle changes serve as a crucial pillar in preventing prediabetes and preventing its progression to type 2 diabetes. 

Exercise

Regular physical activity is a cornerstone in the management of prediabetes. Exercise enhances insulin sensitivity, facilitates glucose uptake by muscles, and helps control body weight. Aim for at least 150 minutes of moderate-intensity aerobic exercise per week, such as brisk walking, cycling, or swimming. Additionally, include strength training exercises at least twice a week to improve muscle mass and metabolic function. Integrating physical activity into daily life can be achieved by choosing stairs over elevators, walking during breaks, and incorporating enjoyable forms of exercise into routines. (14, 52) 

Stress Management

Chronic stress contributes to hormonal imbalances and inflammation, exacerbating prediabetes. Stress reduction techniques, such as mindfulness meditation, deep breathing exercises, and yoga, can help modulate the body's stress response. Schedule short breaks during the day for relaxation, practice mindfulness during meals, and establish a consistent routine that includes moments of calm. Prioritize activities that bring joy and peace, fostering a balanced and resilient approach to daily challenges. (33) 

Sleep

Quality sleep is integral to metabolic health and insulin sensitivity. Aim for 7-9 hours of sleep per night, maintaining a consistent sleep schedule. Create a relaxing bedtime routine, minimize screen time before sleep, and ensure a comfortable sleep environment. Address sleep disturbances by evaluating sleep hygiene, considering factors like room temperature, lighting, and noise. Adequate and restorative sleep positively influences hormonal regulation, supporting efforts to manage prediabetes. (37) 

Supplements and Herbal Remedies for Prediabetes

Supplements and herbal remedies can be valuable adjuncts in supporting metabolic health and addressing prediabetes, but it's crucial to emphasize their role as secondary to lifestyle modifications. While evidence suggests potential benefits for certain supplements like magnesium, chromium, and berberine, they should not be viewed as standalone solutions or replacements for foundational lifestyle changes. Supplements should complement a well-balanced diet rather than replace it.

Before starting new dietary or herbal supplements, consult a healthcare professional to determine their appropriateness based on individual needs, health status, and potential to interact with other medications/supplements. Choose high-quality supplements from reputable sources to ensure purity and potency. Pay attention to dosage recommendations and potential side effects. Periodically assess nutritional status through testing to guide supplement choices. Regular monitoring ensures adjustments based on evolving health needs.

Magnesium

Magnesium plays a critical role in insulin sensitivity and glucose regulation. Research indicates that magnesium deficiency is associated with insulin resistance and an increased risk of type 2 diabetes. Supplementing with magnesium may improve insulin sensitivity and contribute to better glycemic control. Obtain magnesium primarily from dietary sources such as leafy green vegetables, nuts, seeds, and whole grains when possible. Supplements should be considered when dietary intake is insufficient.

Chromium

Chromium is a trace mineral involved in carbohydrate and lipid metabolism. Natural sources of chromium include whole grains, brewer's yeast, and nuts. Some studies suggest chromium supplementation may enhance insulin sensitivity, improve glucose metabolism, and support weight loss. 

Berberine

Berberine, derived from various plants, has shown promise in improving insulin sensitivity and reducing blood glucose levels. Research suggests that berberine does this by activating AMP-activated protein kinase (AMPK), a cellular enzyme involved in energy regulation.

Personalized Treatment Plans for Prediabetes

Treating prediabetes requires a holistic approach. Personalized treatment plans consider the interconnectedness of various body systems and recognize the uniqueness of each person's biochemistry. This approach seeks to identify and correct imbalances in hormonal signaling, gut health, stress responses, and lifestyle factors contributing to metabolic dysfunction. The benefits of personalized medicine include improved patient adherence, targeted interventions, enhanced motivation, and optimized outcomes, potentially leading to more effective prediabetes management and even reversal.

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A Functional Medicine Approach to Prediabetes: Key Takeaways

A holistic approach to prediabetes management underscores the importance of tailoring interventions to the individual unique biochemistry, predisposing their body to metabolic dysfunction. This personalized strategy, encompassing lifestyle modifications, targeted nutritional support, and comprehensive testing, has the potential to address the immediate goal of glycemic control and promote overall well-being by targeting the root causes of metabolic dysfunction. As we move forward, continued research, patient education, and integrating holistic interventions are crucial in refining and advancing our understanding of prediabetes. Embracing this approach to prediabetes management ensures that patients receive comprehensive, individualized care that goes beyond conventional methods, fostering a proactive and empowering approach to health.