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Insulin-Like Growth Factor I
(IGF-1, Somatomedin C) in Blood Spot
Posted: Crown Point, Indiana, Friday, June 10, 2011—
What is IGF-1?
IGF-1, also known as Somatomedin C, is a polypeptide hormone similar in structure to insulin and primarily produced in the liver. It is one of the main mediators of the actions of growth hormone in promoting muscular and skeletal growth. IGF-1 is itself a powerful anabolic hormone, and it also prevents premature cell death by inhibiting apoptosis. Because of its similarity to insulin, it also weakly activates the insulin receptor and therefore has insulin-like effects when present in large quantities. Circulating IGF-1 is almost 100% bound to IGF binding proteins (IGFBP), the most abundant of these being IGFBP-3. These binding proteins stabilize IGF-1, prolonging its
half-life in the bloodstream. Blood levels of IGF-1 are low in young children, peaking during the pubertal growth spurt and then declining steadily with age. IGF-1 is stable in whole blood dried on fi lter paper and therefore can be conveniently and accurately measured in dried blood spots1.
Why Test IGF-1?
Growth hormone (GH) excess or defi ciency Growth hormone (GH) stimulates IGF-1 production in the liver, and therefore IGF-1 levels refl ect average daily levels of GH2. Unlike GH, levels of IGF-1 do not fl uctuate throughout the day. Other hormones affecting IGF-1 levels include thyroxine, cortisol and sex steroids3. The steady decline in GH production with increasing age, subsequent to the pubertal growth spurt,
tends to be associated with an age-dependent decrease in IGF-1 levels. IGF-1 testing can be useful for patients with symptoms of premature aging associated with adult GH defi ciency. It is particularly important to test for IGF-1 whenever GH supplementation is being used to treat premature aging or to improve wellbeing, so that levels are kept within the expected physiological range4,5.
Liver production of IGF-1 is affected by nutritional factors, including protein defi ciency and low insulin levels. Because of this, IGF-1 is a sensitive indicator of nutritional status, and a more useful marker than pre-albumin, retinol-binding protein or transferrin for monitoring patients with eating disorders6,7. A large study8 demonstrated that in underweight and normal weight individuals, IGF-1 levels increase as BMI increases. However, in obese individuals, particularly those with visceral adiposity, IGF-1 levels decrease as BMI increases.
Important new research using the ZRT IGF-1 dried blood spot test has demonstrated its application for assessing a young individual’s cervical skeletal maturation stage9. Until now, peak mandibular bone growth has been assessed on a largely subjective basis using inconvenient and expensive radiography, resulting in radiation exposure. With IGF-1 testing in blood spot, dentists can safely assess a patient’s cervical stage to determine whether a patient has attained or passed the peak pubertal growth, and therefore time orthodontic and other procedures more optimally.
Because of its mitogenic and anti-apoptotic actions, IGF-1 has been implicated in carcinogenesis. High IGF-1 levels have been linked with several types of cancer, including prostate, premenopausal breast, colorectal and lung cancer10. However, meta-analyses show that these associations are modest and variable between research groups11,12 and may be infl uenced by the effects of nutritional factors and BMI on IGF-1 levels13. Recent research has shown that estrogen acts synergistically with IGF-1 to enhance breast cancer cell growth in vitro14. Little is known about these relationships in vivo or if inhibitors of IGF-1 would benefi t breast cancer patients15.
The visceral obesity and related metabolic disturbances that contribute signifi cantly to cardiovascular disease and diabetes risk is frequently a result of neuroendocrine dysregulation, characterized by hormonal imbalances such as increased cortisol levels and suppressed GH secretion16. The generally lower IGF-1 levels associated with increasing obesity8 may be partly a reflection of reduced GH production. Indeed, GH therapy has been used, with promising results, to treat patients with visceral obesity in an attempt to correct endocrine abnormalities and reduce cardiometabolic risk17. While these therapies are not yet widely accepted, it is important to monitor GH supplementation by ensuring that IGF-1 levels stay within the physiological range5. In addition, it is emerging that low IGF-1 levels are also more directly involved in the pathogenesis of insulin resistance, metabolic syndrome, type II diabetes, and cardiovascular disease18. The anabolic role of IGF-1 is mediated by its involvement in increasing insulin sensitivity and peripheral glucose uptake; low IGF-1 levels are associated with poorer blood sugar control and worse cardiovascular outcomes in diabetics19. Increased muscle mass as a result of resistance exercise in sedentary postmenopausal women has been found to be linked with signifi cantly higher IGF-1 levels20,21, which may contribute to the cardiometabolic benefits of resistance training. IGF-1 is now known to have a critical role in vascular protection18,22. This is primarily mediated by IGF-1’s role in increasing nitric oxide bioavailability in the vascular endothelium18,23,24; low IGF-1 levels are therefore thought to reduce vascular protection. Measurement of IGF-1 is now suggested as an important additional marker of cardiovascular disease risk24.
Advantages of a Simple Blood Spot Test
- A simple finger stick provides the few drops of blood required, which are collected on the filter paper provided
- Convenient sample collection at home – no phlebotomist required
- Easy shipment of samples by regular mail – samples are stable for up to a month at room temperature
- Dried bloodspots carry minimal infection risk – infectious agents such as HIV are inactivated in dried blood
- Excellent correlation with serum/plasma IGF-1 levels
- IGF-1 levels are an indicator of growth hormone secretion; low values imply growth hormone defi ciency and high values are seen in acromegaly or gigantism
- Low IGF-1 levels are seen in malnutrition or anorexia, and IGF-1 can be used as a sensitive indicator to monitor nutritional repletion
- Dentists can use IGF-1 levels to assess cervical stage of patients, predict residual facial skeletal growth, and thus properly time orthodontic procedures
- In growth hormone supplementation, IGF-1 levels should be kept within the physiological range to ensure safe dosing levels
- IGF-1 can be used as an adjunct to cardiometabolic risk testing with ZRT’s CardioMetabolic Profi les; low IGF-1 levels are associated with increased risk of cardiovascular disease, especially in individuals with diabetes