Executive Summary
Type II Diabetes Mellitus (T2DM) accounts for chronic hyperglycemia and the body’s inability to efficaciously use insulin, resulting in a condition known as “insulin resistance.”6 Insulin is a hormone which regulates blood sugar levels in the body by entering the blood and absorbing glucose from consumed fat and carbohydrates for use as a source of energy by the body.6 In T2DM, liver, fat tissue, and muscle cells are unable to utilize this insulin appropriately, resulting in insufficient insulin secretion by insulin-producing beta-cells in the pancreas.6 Although a genetic component is inherent to the development of T2DM, various lifestyle/environmental risk factors, such as physical inactivity, poor diet, and consumption of tobacco, account for clinical manifestation of T2DM.
From Bench to Bedside (FBtB) needs to decide upon its research and advocacy funding allocation for the upcoming year. T2DM patient advocates have been vocal in requesting the finest risk assessments to predict T2DM, and FBtB needs to focus on this request for risk identification when deciding upon its investments. Although genome-wide association studies, genetic testing, and genome risk assessments have been highly anticipated by the medical community as risk predictors of T2DM development, clinical use of these tools, which measure genetic variants that are associated with T2DM risk, have demonstrated their unreliability and narrow utility in terms of motivating lifestyle modification after identification of individuals at high T2DM risk. Instead of allocating research and advocacy funding to T2DM genomic testing, FBtB is recommended to fund translation of the Finnish Risk Assessment Score (FINRISK) and biochemical testing models (blood glucose level and oral glucose tolerance assessments), as well as lifestyle counseling, into clinical practice. These tools are currently more accurate at identifying T2DM, comprehensive in terms of genetic and environmental risk factor screening, and inexpensive than genomic testing procedures.
Problem statement
FBtB needs to decide upon its advocacy and research funding allocation for next year and, as the FBtB Board of Directors chooses how to invest its resources to aid in T2DM disease prediction and identification, it must consider the clinical value of T2DM genomic testing and risk assessment. In genomic testing for T2DM, individuals are given a score based on their genetic information that indicates their T2DM risk. Applied use of genomic testing has highlighted its limitations and drawn into question its effectiveness over standard metabolic clinical tools used to predict individual T2DM risk.1,2,3,4,5 FBtB must allocate their research and advocacy funding for the prediction/identification of T2DM thoughtfully to ensure successful translation of their selected risk assessment tool in the clinical setting.
Evidence and Potential Solutions
Initially termed “non-insulin dependent diabetes” or “adult-onset” diabetes, T2DM was renamed due to rising disease incidence among youths; despite this increase in T2DM in young populations, disease onset is later in life than in patients with Type I Diabetes Mellitus, which is characterized by the destruction of pancreatic beta-cells.6 T2DM accounts for approximately 95% of all diagnosed cases of diabetes.6 Various individuals at high risk of developing T2DM include: the elderly, African American and Hispanic/Latino populations, those with a history of gestational diabetes, and individuals whom are obese or have reduced glucose breakdown.6 Clinicians typically advise T2DM patients to take medications and insulin to regulate their blood glucose levels, to exercise regularly, and to adhere to a nutritional alimentary plan in order to lose extraneous weight.2,6 It is imperative that individuals at high risk of T2DM are informed of their disease status and the possibility of pre-diabetic symptoms; T2DM is linked to an increased risk of cardiovascular disease, as well as optical, renal, and nerve complications.6
Despite high initial hopes regarding the predictive use of T2DM genomic risk assessments, recent findings have shown that they are currently of little clinical utility. Because of their low specificity and sensitivity, they are, as of now, translationally insignificant and have not been shown to greatly heighten success of T2DM prediction and identification.2,4 T2DM genetic risk assessments account for identifiable T2DM risk variants within an individual’s genome; these genetic risk variants, known as single-nucleotide polymorphisms (SNPs), account for only 10-15% of T2DM’s genetic inheritance.2,4 Because most T2DM associated SNPs are selected from a narrow region on an individual’s chromosome, are not based on an individual’s genes, and only account for genetic variants of individuals of European descent, they are not considered “causal” and are not encompassing of all populations.2,4,5 In addition, their value at identifying subgroups of individuals whom are potentially at high risk for T2DM—based on family history, sex, age, and weight—is of insignificant value.2,5 Furthermore, statistical analyses of T2DM genetic risk assessments have demonstrated that they accurately predict T2DM in only 54-63% of cases, and not all genetic variants tested via T2DM genomic assessments are relevant in regard to the clinical manifestation of the disease.2,4 Because individuals with a genetic predisposition to T2DM may not develop the disease due to maintenance of healthy lifestyle habits, genetic testing alone is unreliable in predicting individuals who will develop the disease.1 In summary, T2DM genome-wide association studies and risk assessments confer no advantage in identifying individuals at high risk of disease development.
Because individual development of T2DM is based on both nature and nurture, and thus one’s environment as well as his/her genetic composition, genetic risk assessments alone are not sufficient to adequately predict T2DM or to influence healthy behavioral changes in individuals at risk. In contrast, non-invasive clinical testing of metabolic risk factors, such as elevated glucose levels and obesity, have been of specific use in predicting T2DM, and this may result from the hereditary component of T2DM risk factors themselves.1,2,4 In this vein, FINRISK is a screening instrument that records age, weight, height, waist circumference, body mass index (BMI), physical activity, history of hyperglycemia and drug treatments used to reduce high blood sugar levels, as well as daily intake of fruits and vegetables.2,3 Total risk of T2DM development and future antihyperglycemic drug use is then determined; FINRISK assigns a numeric value to each of the aforesaid T2DM risk factors and scores an individual on a range of 0-20, with 20 indicating highest risk of T2DM.3 Once an individual with a high FINRISK score is identified, he/she is suggested to undergo clinical tests, including assessment of fasting blood glucose levels and oral glucose tolerance, to measure biochemical indicators of T2DM.2,3 FINRISK has demonstrated widespread clinical effectiveness at predicting T2DM in recent years, and it is a relatively inexpensive and non-invasive tool that encompasses a variety of natural and nurtured risk factors that have been shown to significantly influence T2DM development in individuals.1 Following identification of high T2DM risk individuals, recent findings have shown that primary lifestyle interventions to prevent disease incidence are advantageous and have been proven to reduce individual BMI, weight, and other risk factors.7
Recommendations
- FBtB is recommended to allocate its research and advocacy funding to implementation of FINRISK within clinical communities, and to supplement use of the FINRISK assessment by providing clinicians with the tools to conduct blood glucose level and oral glucose tolerance testing. These techniques at predicting T2DM have been consistently reliable, especially when paired, to predict T2DM development among individuals with high FINRISK scores, which indicate an individual’s high risk of T2DM based on non-invasive clinical probing alone.
- It is not recommended that FBtB should invest in an effort to advocate for translational research into genetic risk scores as predictors of T2DM risk in the clinical setting. Until causal genes and numerous additional genetic variants linked to T2DM are identified, as well as genetic variants that account for various racial/ethnic populations, genomic testing as a risk predictor of T2DM will remain an expensive, ineffective method of identifying T2DM risk.
- Although the majority of FBtB’s research and advocacy funding should be allocated to providing practitioners with FINRISK assessments and biochemical testing, it is suggested that some funding be allocated to providing funding for lifestyle counseling in clinics to instigate positive, risk-reducing behavioral change among those identified as high risk individuals.