Measuring adiponectin levels to assess type 2 diabetes risk

Approximately seven percent of the United States population is affected by diabetes, and millions are at risk of developing the condition. One in three adults has prediabetes, and 90 percent of them don’t know they have it.^1,2 Fifty percent of people with diabetes die of cardiovascular disease (CVD,) and diabetes is the leading cause of newly diagnosed adult blindness for people between the ages of 20 and 74.^3,4 Early risk assessment is extremely important, as type 2 diabetes can have detrimental long-term consequences, including damage to kidneys, nerves, eyes, and heart, and places an ever-increasing burden on healthcare systems.⁴

Adiponectin and diabetes

Adiponectin is a protein hormone with anti-inflammatory and insulin-sensitizing properties that plays an important role in a number of metabolic processes such as glucose regulation and fatty acid oxidation. Adiponectin levels are inversely correlated with abdominal visceral fat (AVF),⁵ which is the fat that develops around the abdominal cavity, close to many vital organs including the liver, intestines, and pancreas. This visceral fat plays a potentially dangerous role, affecting how hormones function, with high levels having been shown to be a strong indicator of type 2 diabetes, metabolic syndrome, and CVD. Research has found that this type of fat also secretes retinol-binding protein 4 (RBP4), which has been found to increase insulin resistance.

A study published in JAMA,⁵ involving meta-analysis of 13 prospective studies with a total of more than 14,500 participants and 2,623 cases of type 2 diabetes, demonstrated a correlation between increasing adiponectin levels and a declining risk of the disease, across diverse populations. This study highlighted the potential of adiponectin as a risk biomarker.

Traditional methods of measuring risk

Non-biochemical ways in which a patient’s risk of developing type 2 diabetes is evaluated include the consideration of various factors such as gender, age, family history, body mass index (BMI), waist size, and blood pressure. In particular, BMI (the measurement of weight kg/height m2) is commonly used to determine whether a patient is overweight or obese. However, this has proved to be unreliable as a diabetes marker, and it has its limitations when other factors are taken into account, such as age, sex and race. There is a
significant need for a more accurate method of early risk assessment.

With regard to clinical testing, routine tests used to assess risk of type 2 diabetes include measuring fasting plasma glucose (FPG), but this has been shown to have poor specificity; many individuals are identified as having impaired fasting glucose, but their absolute risk of conversion to diabetes is only five percent to 10 percent per year.^6-8 Another common test is the oral glucose intolerance test (OGTT), which is more accurate but is rarely used in practice due to the length of time it takes to perform and because drinking the “Glucola” is unpleasant enough for many patients that it negatively affects compliance. Additionally, oral glucose intolerance can be detected only when the underlying disease has been progressing for many years, which makes the test inadequate for early risk assessment and prevention.⁹

Automated adiponectin assay vs. ELISA

In those contexts it becomes increasingly clear that measuring adiponectin levels is the most accurate way to assess prediabetes. But to become a routine test, it must become one that can be easily used by clinical laboratories. Traditionally, adiponectin has only been available in an enzyme linked immunosorbent assay (ELISA) format, but new research has contributed to the development of adiponectin in an automated format. This means that adiponectin can help to improve efficiencies and facilitate expansion of laboratories and their testing capabilities. ELISAs for clinical testing are notably time- and personnel-consuming, but moving from ELISA to an automated biochemistry method can help to avoid this, as well as increase confidence in clinical results by reducing the risk of error and contamination. Adding automated adiponectin to a routine testing panel can ensure accurate and early diagnosis of prediabetes for a larger population of patients.

Other applications for adiponectin testing

In addition to measuring risk of type 2 diabetes, the measurement of adiponectin levels can also be used to identify women at risk of developing gestational diabetes (GD) in early pregnancy. Interestingly, a study found that women who had a lower adiponectin concentration measured on average six years before pregnancy were associated with a five-fold increased risk of developing GD.^6,10 BMI is often used to assess the risk of developing GD, and women with a BMI of over 30 are urged to maintain a healthy weight before they become pregnant. However, some women develop GD regardless of their BMI, which emphasizes the need for adiponectin testing to ensure a safe and healthy pregnancy for both mother and baby.

To conclude, the need for measuring adiponectin levels has never been greater given the prevalence of the disease and the limitations of traditional means of risk assessment. Early risk assessment is not only vital because of the health implications of diabetes and its complications, but also because, economically, diabetes and its complications bring substantial costs not only for people with diabetes and their families, but for health systems and national economies, both through direct medical expenses and loss of work and wages. It is clear that an improved method for assessing risk, along with a convenient format for routine clinical use, would enable physicians to accurately evaluate more individuals, and as a consequence, lower the percentage of the global population with the disease in the future through lifestyle changes. Such adiponectin assays are for research use only and not for use in diagnostic procedures in the U.S. at present; stay tuned.

References

1. Blonde L. State of diabetes care in the United States. Am J Manag Care. 2007;13 (Suppl. 2):S36–S40.
2. U.S. CDC. About prediabetes and type 2 diabetes. 2016.
3. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Diabetes in America. 3rd Edition. 2016.
4. WHO Media Centre. Diabetes – The problem.
5. Li S, Shin HJ, Ding EL, van Dam, RM. Adionectin levels and risk of type 2 diabetes – a systematic review and meta-analysis. JAMA. 2009;302(2):179-188.
6. Genuth S, Alberti KG, Bennett P, et al. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26(11):3160-3167.
7. Gerstein HC, Santaguida P, Raina P, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. 2007;78(3):305-312.
8. Nichols GA, Hillier TA, Brown JB. Progression from newly acquired impaired fasting glucose to type 2 diabetes. Diabetes Care. 2007;30(2):228-233.
9. Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet. 2008;371(9614):736-743.
10. Hedderson M., Darbinian J, Havel PJ, et al. Low prepregnancy adiponectin concentrations are associated with a marked increase in risk for development of gestational diabetes mellitus. Diabetes Care. 2013;36(12):3930-3937.