Fasting Insulin vs Hemoglobin A1c: Are We Getting It Right?
Recommended screening techniques for diabetes include fasting plasma glucose, oral glucose tolerance testing, glycated hemoglobin, and random plasma glucose levels.
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No primary care provider can deny the impact type 2 diabetes mellitus (T2D) has on the health of its population and the economy of the United States. The American Diabetes Association (ADA) estimates the annual cost of diagnosed diabetes at an astounding $245 billion in the United States.1 The Centers for Disease Control and Prevention estimated that 30.2 million adults — 12.2% of the US adult population — were living with diabetes in 2015, 7.2 million (23.8%) of whom were undiagnosed.2 An additional 84.1 million US adults are prediabetic, with nearly 90% unaware of their condition.2 Imagine the possible impact on patient outcomes and healthcare spending if clinicians could decrease the number of undiagnosed individuals and identify those with prediabetes much earlier.
Current ADA guidelines recommend screening for diabetes and prediabetes in adults with a body mass index (BMI) >25 kg/m2 and the presence of 1 or more risk factors.3 Recommended screening techniques include fasting plasma glucose (FPG), oral glucose tolerance testing (OGTT), glycated hemoglobin (HbA1c), and random plasma glucose levels. Standardized screening of individuals at high risk of developing T2D would ideally reduce the number of those unaware of their prediabetic or diabetic state. However, in a national survey of 1240 primary care physicians, only 52.4% reported following the current national prediabetes screening guidelines.4 This represents missed opportunities to provide early intervention and potentially prevent the progression of prediabetes to T2D.
Due to its convenience, many clinicians have come to rely exclusively on HbA1c for T2D screening. However, HbA1c offers lower sensitivity than other screening tests, and individuals have likely developed significant insulin resistance and pancreatic beta-cell dysfunction by the time it rises significantly.5 Research suggests that a state of insulin resistance occurs before the development of T2D.6 In an effort to maintain glycemic homeostasis, beta cells increase their secretion of insulin to lower blood glucose levels.7 Due to this increased workload, beta cells begin to fail. Failure of beta cells to produce enough insulin to overcome resistance leads to impaired glucose tolerance (IGT) and eventually T2D.6 Identifying prediabetes before this marked beta-cell dysfunction occurs would greatly increase the opportunity for remission or delayed progression to T2D. This pathophysiology suggests that fasting insulin levels could identify insulin resistance long before plasma glucose and HbA1c levels rise.
Current Screening Methods
The ADA and World Health Organization (WHO) offer differing criteria for a diagnosis of prediabetes, neither of which includes fasting insulin levels as a marker of T2D risk. Research has shown varying efficacy for HbA1c, FPG, and OGTT in their ability to detect prediabetes, and differing opinions exist on the best test to screen for prediabetes. Via meta-analysis, Barry et al found the pooled sensitivity of HbA1c to be 0.49 with a specificity of 0.79 and the pooled sensitivity of FPG to be 0.25 with a specificity of 0.94.8 The researchers explained that results of both these tests are highly variable depending on population and setting. Despite OGTT being widely accepted as a more accurate tool for diagnosing T2D, it is time consuming and not widely used for initial screening.8 These limitations of current screening methods underscore the need to find a more efficacious test in terms of ease of use, accuracy, and cost.
This literature review explores what the current published literature demonstrates about the fasting insulin level and whether or not it is efficacious in identifying prediabetes earlier than the traditional screening laboratory assessments (HbA1c, FPG, and 2-hour plasma glucose with OGTT). With nearly half the US adult population being either diabetic or prediabetic, the importance of accurate and early screening methods is obvious. This information will increase providers' knowledge of the efficacy of T2D screening measures and assist clinicians in identifying diabetes or prediabetes risk at its earliest stages. This could potentially increase the number of individuals identified as diabetic or prediabetic and have a profound impact on patient outcomes, disease prevention, and healthcare costs.
The Cochrane Library and EBSCOhost were utilized to search for published literature from 2013 to the present containing information about utilizing a fasting insulin level as a diagnostic tool for diabetes, prediabetes, metabolic syndrome, or insulin resistance in the adult population. Additional articles containing information about the efficacy of current diabetes screening methods or prevention strategies were also reviewed. Articles were excluded if the studies featured nonadult samples. Additionally, non-English publications were not considered.
An initial search of the Cochrane Library for the identified time period focused on articles utilizing the term fasting insulin in the title, abstract, or keywords. The search yielded 12 Cochrane Reviews. The titles and abstracts of these results were reviewed and none were found to be pertinent to the purpose of this review. Additional searches of the Cochrane Library substituted the search term with prediabetes, hyperinsulinism, plasma insulin, blood insulin, and predicting diabetes. None of these searches resulted in the discovery of articles that met the established inclusion criteria.
EBSCOhost was then utilized; the selected databases included Academic Search Complete, CINHAL, and Medline. Searches were limited to articles published from 2013 to 2018. A search for the subject term fasting insulin generated 39 results. Based on title and abstract review, 2 articles were retained due to their potential relevance to the adult population at risk for prediabetes or diabetes. A search for the subject terms blood insulin AND diabetes yielded 356 results with only 2 articles continuing to be included for review after title and abstract examination. A search for the subject terms hyperinsulinism AND prediabetes yielded 25 results; 1 publication met the criteria for inclusion. Additional independent and combined searches of keywords insulin lab, hyperinsulinemia, metabolic syndrome, plasma insulin, and insulin resistance were performed resulting in 5 more articles for inclusion.
A total of 10 articles were determined to meet inclusion criteria for this review of the literature. One article was a systematic review and the others were cross-sectional studies, randomized control trials, prospective studies, and retrospective studies.