Insulin resistance is a common metabolic dysfunction that can lead to various chronic illnesses, including type 2 diabetes, cardiovascular disease, and obesity. Evidence suggests that at least 25% of adults in the United States who don't have diabetes are insulin-resistant.
Insulin resistance occurs when the body's cells fail to respond to insulin. This causes more insulin to be produced, leading to chronically high insulin levels.
While insulin resistance is classically associated with type 2 diabetes mellitus, this article will detail how it can occur in type 1 diabetes mellitus, what causes it, its effects, and how to manage it.
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What Is Insulin Resistance?
Insulin has two main functions within the body:
- Acting as a hormone to reduce blood glucose levels.
- Acting as a signaling molecule for cells in virtually all body organs.
Insulin resistance is a disruption of metabolism that occurs when cells of the body do not respond to insulin stimulation.
To understand insulin resistance, it is necessary to understand the physiology of insulin:
In a healthy patient, insulin is released by the beta cells of the pancreas in response to a rise in blood glucose, which occurs after the ingestion of carbohydrates. When a patient eats carbohydrates, and the body metabolizes them, blood glucose rises. This signals the pancreas to release insulin. Insulin then helps return blood glucose levels to the normal range by telling cells how to use the glucose—either to send it to various organs for energy or to store it as fat (adipose tissue).
However, when this process is dysfunctional, insulin resistance occurs, continually stimulating the pancreas to produce more insulin and causing blood glucose levels to remain consistently elevated.
The Prevalence of Insulin Resistance in Type 1 Diabetes
In past decades, type 1 diabetes mellitus most often began in childhood. Its pathophysiology solely reflected the lack of insulin release from the pancreas, and patients responded completely to treatment with exogenous insulin. Type 2 diabetes mellitus was traditionally seen only in adult patients, and its pathophysiology depended upon the effects of insulin resistance. While the pancreas still produced insulin, the body was resistant to the effects of the insulin it made.
However, the landscape of diabetes pathology has changed. The incidences of overweight and obesity in the cases of type 1 diabetes mellitus continue to increase, which is one factor that has led to a different phenotype that once dominated the disease of type 1 diabetes mellitus.
Despite the common misconception that insulin resistance only affects patients with type 2 diabetes, increasing numbers of patients with type 1 diabetes mellitus develop secondary insulin resistance for many reasons.
In addition, type 1.5 diabetes mellitus has emerged as a pathophysiologic blend of type 1 and type 2 diabetes mellitus. It typically presents in adults with a more gradual onset of illness. Type 1.5 diabetes mellitus includes a degree of autoimmune pancreatic beta cell destruction, causing insulin deficiency and insulin resistance. This requires special considerations in terms of treatment.
Causes of Insulin Resistance in Type 1 Diabetes
Role of Exogenous Insulin
Taking exogenous insulin can result in over-insulinization, as insulin needs fluctuate based on many factors. Endogenous insulin release is designed to physiological needs, supplying the right amount of insulin to meet the body’s demands. However, taking exogenous insulin requires estimated dosing, and over time, exposing the body to excess insulin can lead to decreased cellular response to insulin stimulation.
Diabetes Mellitus Risk Factors
Duration
The duration of type 1 diabetes mellitus significantly influences whether or not insulin resistance is present. A longer duration of type 1 diabetes leads to more exposure to exogenous insulin and a higher likelihood of other metabolic side effects, like obesity, hypertension, and dyslipidemia. These factors increase the risk of developing insulin resistance over time.
Poor Glycemic Control
Poor glycemic control in type 1 diabetes (due to poor diet, limited physical activity, medication side effects, or the presence of autoantibodies) leads to the use of higher doses of insulin. The use of higher doses of exogenous insulin causes weight gain, which can lead to insulin resistance.
Impacts of Other Medical Conditions
Hormonal Changes
Abnormal levels of not only insulin but also other neuroendocrine hormones, including glucagon-like peptide-1 (GLP-1), cortisol, somatostatin, and more, reduce the ability of endogenous insulin to promote optimal glycemic control.
Chronic Inflammation
Chronic inflammation increases the risk of developing insulin resistance. Oxidative stress is an underlying factor in many of these cases because it interferes with insulin signaling and predisposes to hyperglycemia, poor lipid metabolism, and dysregulations in insulin-like growth factor-1. Chronic inflammation also leads to neuroendocrine hormone imbalances, reducing the effect of endogenous insulin on glycemic control.
Overweight and Obesity
Increased consumption of refined carbohydrates and added sugars, a diet overall high in processed foods, and a sedentary lifestyle have led to an increase in overweight and obesity in patients with type 1 diabetes mellitus. While type 1 diabetes was previously characterized by an absolute insulin deficiency, the increased prevalence of overweight and obesity and the adverse metabolic consequences have shifted its pathophysiology also to include insulin resistance.
Metabolic Disease
Metabolic syndrome or its components, including impaired fasting glucose, dyslipidemia, overweight or obesity, and hypertension, increases the risk of developing insulin resistance.
Genetic and Lifestyle Factors
Lifestyle Factors
A diet high in processed foods and refined carbohydrates and a sedentary lifestyle is strongly associated with developing insulin resistance.
Genetic Predisposition
The presence of specific genes has been shown to predispose to insulin resistance. Variations in genes coding for insulin signaling or other genetic factors affecting mitochondrial activity, inflammatory mediators, and lipid metabolism are linked to a greater risk of insulin resistance.
The following are examples of genetic markers that increase the risk for insulin resistance:
- PTB1
- LEPR
- RETN
- SLC2A4
Other Medications
Aside from too much exogenous insulin, other medications can promote insulin resistance. These include:
Addressing Insulin Resistance in Type 1 Diabetes
Lifestyle Modifications
Lifestyle interventions are an important part of managing insulin resistance.
Diet plays a significant role in insulin sensitivity. A healthful diet can help preserve or restore insulin sensitivity, while a poor diet high in refined carbohydrates and proinflammatory foods promotes insulin resistance.
- Prioritizing a diet of whole, nutrient-dense foods while also minimizing refined sugars and processed foods helps regulate blood glucose and improves insulin sensitivity.
- Emphasizing healthy fats, such as omega-3 fatty acids, helps reduce inflammation and improves insulin sensitivity.
- Focusing on high-fiber foods like vegetables, fruits, whole grains, and legumes helps control insulin release and promotes insulin sensitivity.
Regular physical activity is important in promoting insulin sensitivity.
- Cardiovascular exercise improves insulin sensitivity by increasing glucose uptake and utilization in muscles. It also helps with healthy weight maintenance by increasing energy expenditure and promoting fat oxidation.
- Strength training, which includes weight lifting and bodyweight exercises, enhances insulin sensitivity by increasing muscle mass and muscle glucose uptake. Strength training also helps increase and preserve lean body mass, which helps maintain a healthy weight long-term by increasing resting energy expenditure.
Medications and Advanced Therapies
Traditionally, insulin-sensitizing medications, such as metformin and also the newer glucagon-like peptide-1 (GLP-1) receptor agonists, have been used for type 2 diabetes mellitus. While non-insulin therapies are not FDA-approved for use in type 1 diabetes mellitus, evidence suggests insulin-sensitizing medications may be effective in treating insulin resistance in cases of type 1 diabetes mellitus. In addition, GLP-1 receptor agonists may also help regulate glucagon secretion from pancreatic alpha cells.
Health Consequences of Insulin Resistance in Type 1 Diabetes
When insulin resistance occurs in type 1 diabetes mellitus, it increases the risk of other complications:
- Cardiovascular disease
- Obesity
- Non-alcoholic fatty liver disease
- Kidney disease
- Diabetic neuropathy
- Diabetic retinopathy
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Key Takeaways
- Insulin resistance was previously associated with only type 2 diabetes mellitus, but it increasingly affects patients with type 1 diabetes as well.
- Type 1.5 diabetes mellitus has emerged as a blend of the underlying pathophysiologies of type 1 and type 2 diabetes.
- Several risk factors predispose to insulin resistance within type 1 diabetes.
- Many lifestyle changes can help control underlying insulin resistance in any diabetes form.
- Insulin-sensitizing medications may benefit some type 1 diabetes cases where insulin resistance is present.
- Understanding the underlying risk factors and strategies to manage insulin resistance will help prevent potential long-term health consequences associated with insulin resistance in type 1 diabetes.
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