From the Guidelines
Insulin Resistance Causes
Insulin resistance is primarily caused by a combination of genetic predisposition, obesity, physical inactivity, and certain medications, such as glucocorticoids and antipsychotics 1.
Key Factors Contributing to Insulin Resistance
- Genetic predisposition: Plays a significant role in the development of insulin resistance, especially in certain racial and ethnic groups 1.
- Obesity: A major contributor to insulin resistance, particularly when fat is distributed around the abdominal area 1.
- Physical inactivity: Lack of physical activity can lead to insulin resistance, as regular exercise helps improve insulin sensitivity 1.
- Medications: Certain medications, including glucocorticoids (e.g., prednisone) and antipsychotics (e.g., olanzapine), can contribute to insulin resistance 1.
- Hormonal imbalances: Conditions like polycystic ovary syndrome (PCOS) and Cushing's syndrome can also contribute to insulin resistance 1.
Other Factors
- Age: The risk of developing insulin resistance increases with age 1.
- Family history: Having a first-degree relative with type 2 diabetes or insulin resistance increases the risk 1.
- Racial and ethnic factors: Certain racial and ethnic groups are more prone to developing insulin resistance and type 2 diabetes 1.
- Lifestyle factors: A diet high in saturated fats and sugars, and low in fiber, can contribute to insulin resistance 1.
Conclusion is not allowed, so the response ends here.
From the Research
Causes of Insulin Resistance
The causes of insulin resistance are multifaceted and involve various physiological and pathophysiological factors. Some of the key causes include:
- Genetic predisposition 2, 3
- Obesity, which leads to the release of non-esterified fatty acids, glycerol, hormones, and pro-inflammatory cytokines that contribute to insulin resistance 4, 3
- Disturbances in sleep, such as sleep apnea 5
- Ovarian dysfunction, particularly in women with polycystic ovary syndrome (PCOS) 5, 2
- Endoplasmic reticulum stress, adipose tissue hypoxia, oxidative stress, lipodystrophy, and other metabolic and vascular changes 4, 3
- Age and disease-related factors, such as type 2 diabetes, hypertension, and nonalcoholic fatty liver disease 6, 3
- Drug effects and other environmental influences 3
Molecular Mechanisms
At a molecular level, insulin resistance involves defects in insulin signaling, including:
- Reduced insulin receptor tyrosine kinase activity 5
- Reduced post-receptor phosphorylation steps that impinge on metabolic and vascular effects of insulin 5
- Increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary 2
- Constitutive activation of serine kinases in the MAPK-ERK pathway that may contribute to resistance to insulin's metabolic actions in skeletal muscle 2
Associated Conditions
Insulin resistance is associated with various metabolic and cardiovascular conditions, including: