Insulin resistance type 1
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Insulin Resistance in Type 1 Diabetes: An Overview
Introduction to Insulin Resistance in Type 1 Diabetes
Insulin resistance, commonly associated with Type 2 diabetes, is increasingly recognized as a significant factor in Type 1 diabetes (T1D) as well. This condition not only complicates the management of T1D but also contributes to the development of both macrovascular and microvascular complications1 2.
Pathophysiology and Measurement Challenges
Insulin Resistance Mechanisms
In T1D, insulin resistance can be attributed to several factors, including impaired muscle adenosine triphosphate (ATP) synthesis, enhanced oxidative stress, and abnormal glycogen metabolism in the liver3. Additionally, increased lipid availability in muscle tissue has been shown to contribute to insulin resistance through specific biochemical pathways3.
Measurement Difficulties
Measuring insulin resistance in T1D is complex due to the intertwined relationship between β-cell function and insulin sensitivity. This relationship complicates the interpretation of insulin secretion data, especially in the context of prevention or intervention trials2. Clinical factors such as hypertension, waist-to-hip ratio, and lipid levels have been used to develop an insulin resistance syndrome (IRS) score, which has shown a significant correlation with glucose disposal rates7.
Clinical Implications and Management Strategies
Impact on Disease Progression and Complications
Insulin resistance in T1D is an independent risk factor for the development of vascular complications. It is also implicated in the disease's progression, particularly during periods of increased physiological stress such as puberty or illness1 2. Intensive diabetes management has been associated with improved insulin sensitivity and β-cell function, highlighting the importance of addressing insulin resistance in T1D management2.
Therapeutic Approaches
Several strategies have been explored to manage insulin resistance in T1D. Lifestyle modifications and the use of metformin have shown promise in improving whole-body insulin sensitivity by 20%-60%3. Intensive insulin therapy and islet transplantation have also been effective, although they do not completely restore insulin sensitivity3. The INTIMET study is currently investigating the effects of metformin on tissue-specific insulin resistance in adults with T1D8.
Unique Features and Genetic Considerations
Tissue-Specific Insulin Resistance
Research has identified significant insulin resistance in both hepatic and skeletal muscle tissues in individuals with T1D. This resistance persists even after normalizing glucose levels through overnight insulin infusion, indicating that factors beyond hyperglycemia contribute to insulin resistance in T1D9.
Genetic Factors
Mutations in the INSR gene, which encodes the insulin receptor, can lead to severe insulin resistance syndromes that may be misdiagnosed as T1D. These cases highlight the importance of considering genetic testing in patients with atypical presentations of diabetes5.
Conclusion
Insulin resistance is a critical and often under-recognized component of Type 1 diabetes. It plays a significant role in the disease's pathogenesis and complications, necessitating targeted management strategies. Ongoing research and clinical trials are essential to better understand and address insulin resistance in T1D, ultimately improving patient outcomes.
Sources and full results
Most relevant research papers on this topic
Addressing insulin resistance in Type 1 diabetes
Insulin resistance in Type 1 diabetes contributes to the development of complications and may be treated with safe and effective measures, such as metformin.
Systematic Review
Very Rigorous Journal
Highly CitedInsulin resistance in type 1 diabetes
Insulin resistance plays a larger role in type 1 diabetes than commonly recognized, and intensive diabetes management is associated with improved insulin sensitivity and cell function.
Highly CitedInsulin resistance in type 1 diabetes mellitus.
Insulin resistance is a feature of type 1 diabetes, with lifestyle modifications and metformin increasing whole-body insulin sensitivity by 20%-60%.
Non-RCTHighly CitedInsulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis.
Insulin resistance is a prominent feature in patients with type 1 diabetes mellitus, affecting hepatic, peripheral, and adipose tissues.
Meta-Analysis
Rigorous JournalHighly Cited1136-P: Type A Insulin Resistance Masquerading as Type 1 Diabetes Mellitus
A 19-year-old male with type A insulin resistance due to a mutation in the INSR gene was initially presumed to have type 1 diabetes, but genetic testing revealed a mutation in the insulin receptor gene.
Case ReportManagement of Severe Insulin Resistance in Patients with Type 1 Diabetes
Novel strategies in insulin formulations, lifestyle modification, adjunct therapies, and surgery may help better manage severe insulin resistance in patients with type 1 diabetes.
Literature ReviewCan clinical factors estimate insulin resistance in type 1 diabetes?
Clinical risk factors can identify individuals with type 1 diabetes who are insulin resistant, and a score based on these factors can determine the extent of insulin resistance in type 1 diabetes.
Observational StudyHighly CitedInsulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double‐blind placebo‐controlled, randomised trial
Metformin may improve insulin sensitivity in adults with Type 1 diabetes, potentially reducing cardiovascular risk.
RCTRigorous JournalFeatures of hepatic and skeletal muscle insulin resistance unique to type 1 diabetes.
Insulin resistance in liver and skeletal muscle is a significant feature in type 1 diabetes, but its cause remains unidentified and unrelated to body mass index, fat, lipids, visceral fat, and physical activity.
Non-RCTHighly Cited