Diabetes mellitus is a metabolic disease involving inappropriately elevated blood glucose levels. Globally, one in 11 adults has diabetes mellitus, with 90% of cases classified as type 2 (34). A less common subclassification, known as type 1.5 diabetes, is commonly misdiagnosed as type 2 diabetes. However, early recognition and treatment of type 1.5 diabetes is important because this form of diabetes has an autoimmune component, leading to the permanent destruction of pancreatic cells responsible for secreting insulin and insulin dependence. This article will discuss the key features of type 1.5 diabetes and how functional medicine doctors address this complex disease. 

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What is Type 1.5 Diabetes?

Type 1.5 diabetes is the unofficial name for latent autoimmune diabetes in adults (LADA). This is a form of diabetes that shares characteristics with both type 1 and type 2 diabetes mellitus. It is often misdiagnosed as type 2 diabetes initially because it has a later onset, manifesting in adults. However, LADA is actually an autoimmune condition like type 1 diabetes, where the immune system attacks and destroys the insulin-producing beta cells in the pancreas. Approximately 10% of phenotypic type 2 diabetic patients are positive for at least one of the islet autoantibodies. While LADA has many genetic and immunological similarities with type 1 diabetes, differences in autoantibody clustering, T cell reactivity, and genetic susceptibility distinguish LADA as a distinct variant of type 1 diabetes. (27) 

Important key features of LADA to recognize include:

• Age of Onset: LADA typically develops in adults, usually after age 30, although it can occur at any age.
• Autoimmune Component: LADA involves the immune system producing diabetes-associated autoantibodies that mistakenly attack the beta cells in the pancreas, resulting in a gradual decline in insulin production over time. 
• Insulin Resistance: Insulin resistance is a physiological condition in which the body's cells become less responsive to the effects of insulin. Insulin is the hormone responsible for regulating blood sugar levels and facilitating glucose uptake into cells for energy. LADA may have some degree of insulin resistance, a hallmark feature of type 2 diabetes. (4, 18)
• Insulin Requirement: People with LADA typically have a poorer response to oral medications commonly used to treat type 2 diabetes. While these patients may not require insulin treatment at diagnosis, they usually progress to insulin dependence after several months to years. (31) 

Type 1.5 Diabetes Signs & Symptoms

The broad characteristics of LADA that help in making the diagnosis include:

• Adult-onset diabetes (age at diagnosis is over 30 years)
• Family or personal history of autoimmunity
• Compared to patients with type 2 diabetes, type 1.5 is associated with a reduced frequency of metabolic syndrome: lower HOMA-IR (homeostasis model assessment of insulin resistance) score, BMI (body mass index), blood pressure, and normal HDL cholesterol.
• C-peptide levels decrease more slowly than in patients with type 1 diabetes.
• Positivity for diabetes-associated autoantibodies, most commonly anti-GAD65 (glutamic acid decarboxylase 65) and ICA (islet-cell antibodies)
• Non-insulin requiring at the onset of diabetes

Patients with LADA will complain of similar symptoms as those with type 1 or 2 diabetes:

• Increased thirst (polydipsia)
• Urinary frequency (polyuria)
• Increased appetite (polyphagia)
• Blurred vision
• Unexplained weight loss
• Frequent infections
• Weakness and fatigue
• Dry, itchy skin
• Numbness and tingling in the hands and feet (neuropathy) 

What Are The Possible Causes of Type 1.5 Diabetes?

The exact cause of LADA is not fully understood, and the specific mechanisms that lead to it are complex and continue to be an area of active research. Both genetic and environmental factors play a role in determining an individual's susceptibility to and likelihood of developing an autoimmune disease. As in type 1 diabetes, certain HLA variants hold the most weight in deciding the genetic risk for LADA. HLA genes code for major histocompatibility (MHC) proteins, which have important immunoregulatory functions; variations in these genes precipitate immune dysregulation. (33) 

Environmental and lifestyle factors also contribute to the development of LADA in genetically susceptible individuals, including excess body weight, greater waist-hip ratio, low birth weight, intake of two or more sweetened beverages or cups of coffee daily, and smoking. (33) 

From a functional medicine perspective, it is understood that common underlying triggers for all autoimmune diseases include environmental toxins, physiologic stress, intestinal permeability and dysbiosis, hormonal imbalances, and infection. 

Functional Medicine Labs to Test for Root Cause of Type 1.5 Diabetes

Diagnosis of LADA includes establishing blood sugar levels within the diabetic range with the presence of diabetes-associated antibodies. A standard laboratory evaluation for LADA should include, at minimum, fasting glucose, hemoglobin A1c, and GAD65 antibodies. Ordering fasting insulin, an oral glucose tolerance test, and C-peptide can also help quantify the degree of insulin resistance and deficiency present.

Once a patient has been diagnosed with LADA, functional medicine providers typically order additional specialty labs that dive deeper to understand the underlying mechanisms contributing to autoimmunity. These results help guide comprehensive and integrative treatment plans to enhance patient response to treatment and positive clinical outcomes.

Hormone Testing

The DUTCH Plus is a comprehensive hormone panel that analyzes 35 hormones and their metabolites, including estrogen, testosterone, DHEA-S, and cortisol. In addition, this test measures the cortisol awakening response (CAR) and organic acids. Together, this panel helps to screen for hormonal imbalances, dysfunction in circadian rhythm, inflammation, and nutrient deficiencies as triggers for autoimmune disease.  

Patients with autoimmune disease and diabetes have a high risk of autoimmune thyroid disease. Thyroid dysfunction has also been implicated in disrupting the stress response, sex hormone balance, gut health and function, and immune balance (8). A comprehensive thyroid panel, including TSH, free T3 and T4, and thyroid antibodies, can detect thyroid disorders and autoimmunity.

Comprehensive Stool Analysis

A comprehensive stool test is a beneficial tool in assessing intestinal dysbiosis and permeability. Using culture, PCR, and microscopic laboratory methods, comprehensive stool tests analyze a  stool sample to detect and quantify the presence of beneficial and harmful bacteria, viruses, parasites, and yeast. Zonulin is a biomarker easily added to the test if not already included. Zonulin is a protein that controls the tight junctions between intestinal epithelial cells; increased levels are associated with enhanced intestinal permeability ("leaky gut"). 

Environmental Toxin Panel

A variety of environmental toxin tests are available, depending on what type of toxic exposure you are screening for. These tests generally require a urine or hair sample to screen for heavy metals, chemicals, and mycotoxins. The body's total toxic load is determined by past and present exposures and the body's ability to effectively detoxify and eliminate those toxins through the gut, kidneys, liver, and skin. Therefore, in addition to the toxin panel, ordering kidney and liver function panels can help assess the health of these organs.

Additional Lab Tests 

Uncontrolled diabetes can lead to health complications, including heart disease, chronic kidney disease, nerve damage, poor wound healing, and problems with oral health and vision. To mitigate and screen for these risks, it is recommended that diabetic patients have an annual foot and neurological exam, dilated comprehensive eye exam, lipid panel, and comprehensive metabolic panel (CMP). 

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Conventional Treatment for Type 1.5 Diabetes

Given that LADA shares characteristics with both type 1 and type 2 diabetes, treatment blends strategies from both types of diabetes. Treatment goals are aimed at achieving optimal blood sugar control, minimizing the risk of health complications, and preserving pancreatic insulin-secreting capacity. Treatment options continue to evolve as more evidence is published to explain the complexities of this disease; current recommendations support the use of lifestyle modifications, oral hypoglycemic agents, and insulin therapy to achieve treatment goals. 

Functional Medicine Treatment Protocol for Type 1.5 Diabetes

Using functional medicine labs to uncover the underlying reasons behind autoimmunity, a functional medicine provider will incorporate additional modalities to correct immune dysregulation and use pharmacologic and natural interventions to manage blood sugar. 

Therapeutic Diet and Nutrition Considerations for Type 1.5 Diabetes

Reducing carbohydrate intake is a primary goal in dietary modifications for balancing blood sugar. The Standard American Diet (SAD) is high in processed foods, simple carbohydrates, and added sugars. Not only does this diet contribute to blood sugar dysregulation, characterized by rapid peaks and dips in blood sugar after meals, but this nutrient-poor diet also contributes to systemic inflammation and higher rates of cardiovascular and autoimmune disease. Eating a diet that emphasizes low glycemic, complex carbohydrates over simple and refined carbohydrates is associated with reduced risk of diabetes, better weight management, and reduced levels of inflammation. Ensuring adequate protein intake by eating lean protein and increasing intake of unsaturated fats with meals is also helpful in stabilizing blood sugar and improving insulin sensitivity. (13, 19, 25) 

Making dietary changes can be challenging and feel overwhelming. To simplify matters and help patients make healthy nutritional choices regarding blood sugar management, the American Diabetes Association developed the Diabetes Plate Method as a practical and visual approach to meal planning to help individuals promote balanced nutrition and portion control.

Another important aspect of treating Type 1.5 diabetes is dampening inflammation to address the autoimmune component. Anti-inflammatory diets focus on eliminating foods that promote inflammation and incorporating foods that reduce it. Diets that emphasize the consumption of whole fruits, vegetables, lean proteins, unsaturated fats, whole grains, legumes, tea, coffee, herbs, and spices are considered anti-inflammatory. The Mediterranean, DASH, and plant-based diets are all considered anti-inflammatory and have also been shown to support healthy blood sugar levels (14).  

Supplements Protocol for Type 1.5 Diabetes

The following supplements can be considered part of an integrative treatment plan to improve blood sugar levels and insulin sensitivity and modulate the immune system. 

Chromium

Chromium is a trace mineral that plays a role in insulin action and glucose metabolism. Studies investigating chromium supplementation's effects on diabetes have shown benefits in terms of improved glycemic control, reduced insulin resistance, and lower fasting blood sugar levels.

Dose: 200 mcg three times daily

Duration: 4-25 weeks

Magnesium

Magnesium is an essential mineral involved in over 300 enzymatic reactions in the body. Magnesium deficiency has been shown to increase the risk of diabetes, and supplementation can protect against inflammation, improve markers of blood glucose control and insulin sensitivity, and lower blood pressure. (20, 38) 

Dose: 300 mg daily

Duration: 3 months

Vitamin D

Vitamin D deficiency has been associated with autoimmune diseases, including type 1 diabetes, and supplementation has been proven helpful in treating autoimmunity (16). This systematic review calculated a diabetes risk reduction of 15% with vitamin D supplementation.

Dose: 4,000 IU daily

Duration: Ongoing

Ashwagandha

Ashwagandha is an adaptogenic herb used historically to assist with stress, neuroprotection, and inflammation. Studies have shown that its administration effectively treats chronic stress and hypothyroidism, known contributors to autoimmune disease. Additionally, its immunomodulatory effects have been shown to balance the immune system by inducing changes in the circulating amounts of immunoglobulins and cytokines.

Dose: 500-600 mg daily, in split dosing

Duration: 8 weeks

When To Retest Labs

At-home daily self-monitoring of fasting and post-prandial glucose levels is essential to monitor how well the treatment works and adjust insulin doses for patients requiring insulin replacement therapy. HbA1c should be monitored every three months until the patient consistently meets blood sugar goals. Other specialty labs can be reordered to monitor treatment efficacy, typically anywhere from 3-12 months after initiating a treatment protocol specific to that lab.

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Summary

The diagnosis and root-cause treatment of type 1.5 diabetes, or LADA, presents a multifaceted approach to address the complex interplay between genetics, autoimmune factors, and metabolic dysregulation. As our understanding of LADA continues to evolve, integrating functional medicine principles into its management holds great promise. Personalized therapeutic strategies focus on identifying and addressing root causes, optimizing nutrition, promoting gut health, and modulating the immune response.