Does having Mast Cell Activation Syndrome (MCAS) and a family history of type 2 diabetes increase the risk of developing insulin resistance and postprandial hyperglycemia?

From the Guidelines

Having Mast Cell Activation Syndrome (MCAS) and a family history of type 2 diabetes likely increases your risk of developing insulin resistance and postprandial hyperglycemia. MCAS involves chronic inappropriate activation of mast cells, which release inflammatory mediators like histamine, cytokines, and prostaglandins throughout the body. This chronic inflammation can directly interfere with insulin signaling pathways, potentially leading to insulin resistance, as supported by the most recent guidelines on diabetes management 1. When combined with a genetic predisposition to type 2 diabetes from family history, these factors may compound each other. The inflammatory state from MCAS can exacerbate the underlying genetic tendency toward metabolic dysfunction.

Key factors to consider include:

• The role of insulin resistance in the development of type 2 diabetes, as outlined in recent studies 1
• The impact of family history on the risk of developing type 2 diabetes, with a strong genetic predisposition being a significant risk factor 1
• The potential for MCAS to contribute to metabolic dysfunction through chronic inflammation, which can affect insulin signaling pathways

For individuals with both conditions, regular monitoring of blood glucose levels is advisable, including both fasting and postprandial measurements. Following an anti-inflammatory diet low in simple carbohydrates, regular physical activity, maintaining a healthy weight, and working with healthcare providers to effectively manage MCAS symptoms may help reduce the risk of developing insulin resistance. Additionally, some medications used to treat MCAS, particularly corticosteroids, can themselves affect blood glucose levels, further highlighting the importance of comprehensive monitoring and management, as noted in guidelines on diabetes care 1.

From the Research

Insulin Resistance and Postprandial Hyperglycemia

• Having Mast Cell Activation Syndrome (MCAS) and a family history of type 2 diabetes may increase the risk of developing insulin resistance and postprandial hyperglycemia, as suggested by studies on the role of mast cells in diabetes 2 and the impact of family history on type 2 diabetes risk 3.
• Mast cells are implicated in innate and acquired immunity, inflammation, and metabolic disorders such as diabetes, and their activation can lead to the release of inflammatory mediators and cytokines/chemokines 2.
• A family history of type 2 diabetes is a strong risk factor for the disease, and this risk is not fully explained by anthropometric, lifestyle, or genetic risk factors 3.

Role of Mast Cells in Diabetes

• Mast cells are thought to play a role in the development of insulin resistance and postprandial hyperglycemia, as they are activated in response to inflammatory stimuli and release histamine and other mediators that can impair insulin signaling 2.
• The activation of mast cells can lead to the release of histamine, which can increase glucose production in the liver and impair insulin sensitivity 2.
• Studies have shown that mast cell-deficient mice have improved insulin sensitivity and glucose tolerance, suggesting that mast cells may play a role in the development of insulin resistance and postprandial hyperglycemia 2.

Impact of Family History on Type 2 Diabetes Risk

• A family history of type 2 diabetes is a strong risk factor for the disease, and this risk is increased if the family history is biparental or if the parents were diagnosed with diabetes at a younger age 3.
• The risk of type 2 diabetes associated with family history is not fully explained by established risk factors such as BMI, waist circumference, or genetic risk score 3.
• People with a positive family history of type 2 diabetes may be more likely to develop risk awareness and engage in risk-reducing behaviors, but more research is needed to understand how people personalize and process their familial risk 4.

Postprandial Hyperglycemia and Insulin Resistance

• Postprandial hyperglycemia is a characteristic feature of insulin resistance and can induce oxidative stress generation, vascular inflammation, and platelet activation, increasing the risk of cardiovascular diseases 5.
• Acarbose, an alpha-glucosidase inhibitor, has been shown to improve postprandial hyperglycemia and reduce the risk of development of type 2 diabetes in patients with impaired glucose tolerance 5.
• The prevention of postprandial hyperglycemia may be a promising therapeutic strategy for reducing the increased risk of diabetes, hypertension, dyslipidemia, obesity, and cardiovascular diseases in patients with the metabolic syndrome 5.