Insulin resistance refers to the bodies inability to adequately respond to secreted insulin.
Primary insulin signaling defects are genetic, or acquired, disorders in which, signaling by insulin is impaired upstream, at the level, or downstream of the insulin receptor.
Primary insulin signaling defects that occur upstream of the insulin receptor are caused by insulin antibodies that bind to circulating insulin.
Insulin antibodies impair the ability of insulin to interact with its receptor, leading to hyperglycemia.
Primary insulin signaling defects that occur at the level of the insulin receptor are caused by mutations in the receptor or by antibodies that target that receptor: these disorders manifest as an autosomal recessive syndrome, with growth and developmental disorders.
Primary insulin resistance effects that occur downstream of the insulin receptor arise from mutations involving the insulin cascade and is observed in patients with obesity and lipodystrophy.
Physiologic insulin secretion, approximates 0.4 to 1 unit per kilogram of bodyweight per day.
An exogenous insulin requirement greater than two or three units of insulin per kilogram per day is classified as severe insulin resistance.
It often occurs in conjunction with obesity, hypertension, and dyslipidemia, is part of the metabolic syndrome.
Puberty, pregnancy, and older age are risk factors associated with insulin resistance.
Fundamental abnormality of type 2 diabetes and of obesity.
It is present in most, but not all, obese and elderly individuals and even in some young and thin persons.
Overt insulin resistance contributes to beta cell destruction in the relative insulin deficit, manifest thing is hypoglycemia and leads to type two diabetes.
Approximally 10% of normal weight adults have insulin resistance.
It is a precursor to and an accelerant to other conditions such as type two diabetes, atherosclerosis, non-alcoholic fatty liver disease and probably obesity-associated cancers.
Fitness reduces the risk for insulin resistance and may be most beneficial among obese individuals.
Associated with hyperinsulinemia, a process that may promote abdominal fat storage, increased triglyceride levels referred to as the insulin resistance syndrome.
Associated with ectopic lipid deposition in skeletal muscle and liver.
Signs of insulin resistance that occur due to cross-reactivity of high circulating levels of insulin with the insulin like growth factor1 1 receptor and includes acantholysis nigricans, skin tags, and acromegaly like features.
Indulin resistance is related to physical inactivity, overweight, obesity, cardiovascular, cerebral vascular, and peripheral vascular disease.
Insulin resistance can occur in association with acute stress, and organ damage, weight gain, obesity, or starvation.
Characterized insufficient glucose response to a given concentration of insulin.
Medications may contribute to a reduced responsiveness of the glucose lowering effects of insulin and include: glucocorticoids, atypical antipsychotic meds, and antiviral therapy for HIV.
A glucogonoma, Cushing’s syndrome, and acromegaly or endocrine disorders involving hormonal hypersecretion that can lead to insulin resistance.
Severe insulin resistance defined asinsulin requirement greater than 200 units per day.
Insulin resistance predates beta cell dysfunction and plays a major role in the pathogenesis of type two diabetes, although impaired beta cell function is ultimately responsible for progression to hyperglycemia.
Contributing factors are obesity, metabolic syndrome, stress, amd glucocorticoid exposure.
The combined presence of impaired fasting glucose and elevated triglycerides is a better predictor of insulin resistance and impaired fasting glucose alone.
Triglyceride to high density lipoprotein cholesterol ratio, especially 3.5 or higher, strongly related to insulin resistance, and is a major factor in the metabolic syndrome, and is a strong picture of coronary heart disease, cardiovascular disease, and all cause mortality.
Adipose tissue stores lipids in the form of triglycerides, slowly releasing them into the bloodstream when insulin is low.
In insulin-resistant adipose tissue-obesity and type 2 diabetes-more triglycerides are broken down into FFAs and released into the bloodstream, promoting uptake by the liver.
Autoimmunity is a rare cause severe insulin resistance and is associated with a high mortality.
Type B insulin resistance results from autoantibody formation against the insulin receptor and has a reported mortality rate of 54% at10 years.
Patients with type B insulin resistance develop severe insulin resistance and blood sugar derangements.
Type B insulin resistance most commonly noted in black females and is manifested by weight loss, diffuse acanthosid nigricans, and hyperandrogen in females.females.
Type B insulin resistance on rheumatologic conditions.
Type B insulin resistance distinguished by a low triglyceride level and a adiponectin level of greater than 7 mg/L.
Insulin resistance in type 2 diabetes, triglyceride levels are often elevated and adiponectin is low.
Studies suggest that systemic insulin resistance or high circulating levels of insulin is accompanied by brain insulin resistance.
Metabolic derangements may affect brain structure and function and promote neurodegenerative disorders: in dementia free older adults, raised serum insulin and insulin resistance are related to worse cognitive function seven years later. (Hooshmand B).
The mechanism linking inflammation with insulin resistance is believed to be partly a result of excess glucose- and free fatty acid–induced stress to insulin-sensitive tissues, particularly adipose and liver, leading to the production of inflammatory cytokines such as TNFα, interleukin-1β, and IL-6, which further promote inflammation in other tissues, including muscle and islet cells.
Following carbohydrate ingestion, glucose is deposited primarily in muscle and the liver as glycogen, and impairment in insulin responsiveness in these organs results in fasting and postprandial hyperglycemia.
Insulin-resistant skeletal muscle is not as efficient at taking up glucose from the bloodstream after a meal.
Markers include high circulating levels of C-peptide and insulin like growth factor binding protein 1 (IGFBP1).
Markers of high circulating levels of C-peptide and insulin like growth factor binding protein1 (IGFBP1) directly associated with risk of colorectal cancer.
Magnesium supplementation increases insulin sensitivity among healthy patients and type 2 diabetics.
Noted with burns, trauma, sepsis, surgery and pain.
Associated with acanthosis nigricans.
Prevalence in 10-25% of the population, depending on the body weight of the population.
Weight loss increases insulin sensitivity and is proportional to the degree of weight loss, and can range from 20% to 200%.
A few weeks of exercise can enhance insulin sensitivity by ~20% in previously sedentary obese adults, independent of weight loss.
Physical activity is associated with improved insulin sensitivity, and physical inactivity is associated with an increased insulin resistance.
Elevated levels of insulin in the portal circulation increase free androgen levels and enhance LH stimulated ovarian androgen secretion accounting for androgen excess in polycystic ovary syndrome.
Associated with hypertension indicating that patients with essential hypertension have higher fasting and postprandial insulin levels than normotensive patients.
Associated with puberty.
90 minutes of aerobic exercise combined with 60 minutes of resistance exercise over 3 days per week is optimum to reduce insulin resistance and improve function on previously sedentary older abdominally obese adults (Davidson).
Aerobic exercising increases insulin sensitivity of muscle and improvement in glucose homeostasis.
Inactivity may cause the conversion of skeletal muscle myofibers to convert to the fast switch phenotype, making such fibers less able to perform sustained aerobic and contributing to an insulin resistant state.
Lipid accumulation in muscle and liver are related to insulin resistance and promote nonalcoholic fatty liver disease, atherogenic dyslipidemia and hepatic lipogenesis.
This inefficient glucose uptake in muscle with insulin resistance promotes the redistribution of consumed carbohydrates from glucose destined for use in glycogen stores in the skeletal muscles to being used as a substrate for de novo lipogenesis in the liver.
There is a strong relationship between intramyocellular lipid content and insulin resistance in muscle.
Pseudoresistance is a mimic of insulin resistance and is related to poor adherence to insulin therapy, excessive carbohydrate consumption, when insulin is administered subcutaneously where scar tissue or soft tissue edema is present, and the use of expired or not stored properly insulin.