nutrients Article Predicting Malnutrition Risk with Data from Routinely Measured Clinical Biochemical Diagnostic Tests in Free-Living Older Populations Saskia P. M. Truijen 1 , Richard P. G. Hayhoe 1,2 , Lee Hooper 1 , Inez Schoenmakers 1, Alastair Forbes 1 and Ailsa A. Welch 1,* 1 Department of Epidemiology and Public Health, Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK; [email protected] (S.P.M.T.); [email protected] (R.P.G.H.); [email protected] (L.H.); [email protected] (I.S.); [email protected] (A.F.) 2 School of Allied Health, Faculty of Health, Education, Medicine and Social Care, Anglia Ruskin University, Chelmsford CM1 1SQ, UK * Correspondence: [email protected]; Tel.: +44-(0)1603-591950 Abstract: Malnutrition (undernutrition) in older adults is often not diagnosed before its adverse consequences have occurred, despite the existence of established screening tools. As a potential method of early detection, we examined whether readily available and routinely measured clinical biochemical diagnostic test data could predict poor nutritional status. We combined 2008–2017 data of 1518 free-living individuals ≥50 years from the United Kingdom National Diet and Nutrition Survey (NDNS) and used logistic regression to determine associations between routine biochemical Citation: Truijen, S.P.M.; Hayhoe, diagnostic test data, micronutrient deficiency biomarkers, and established malnutrition indicators R.P.G.; Hooper, L.; Schoenmakers, I.; (components of screening tools) in a three-step validation process. A prediction model was created to Forbes, A.; Welch, A.A. Predicting determine how effectively routine biochemical diagnostic tests and established malnutrition indica- Malnutrition Risk with Data from Routinely Measured Clinical tors predicted poor nutritional status (defined by ≥1 micronutrient deficiency in blood of vitamins B6, Biochemical Diagnostic Tests in B12 and C; selenium; or zinc). Significant predictors of poor nutritional status were low concentrations Free-Living Older Populations. of total cholesterol, haemoglobin, HbA1c, ferritin and vitamin D status, and high concentrations of Nutrients 2021, 13, 1883. https:// C-reactive protein; except for HbA1c, these were also associated with established malnutrition indi- doi.org/10.3390/nu13061883 cators. Additional validation was provided by the significant association of established malnutrition indicators (low protein, fruit/vegetable and fluid intake) with biochemically defined poor nutritional Academic Editor: status. The prediction model (including biochemical tests, established malnutrition indicators and Riccardo Caccialanza covariates) showed an AUC of 0.79 (95% CI: 0.76–0.81), sensitivity of 66.0% and specificity of 78.1%. Clinical routine biochemical diagnostic test data have the potential to facilitate early detection of Received: 31 March 2021 malnutrition risk in free-living older populations. However, further validation in different settings Accepted: 25 May 2021 and against established malnutrition screening tools is warranted. Published: 31 May 2021 Keywords: micronutrient deficiency biomarker; biochemical diagnostic tests; screening tool; under- Publisher’s Note: MDPI stays neutral nutrition with regard to jurisdictional claims in published maps and institutional affil- iations. 1. Introduction Malnutrition (or “undernutrition”) is a major cause of poor health in older age and is associated with loss of body weight and skeletal muscle mass. As such, it is linked with Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. sarcopenia [1], the loss of skeletal muscle mass and function with age [2] and reduced This article is an open access article immuno-resilience [3], as well as with frailty, falls and fractures [4–6] and premature distributed under the terms and mortality [7,8]. Malnutrition is estimated to affect more than 3 million individuals in the conditions of the Creative Commons United Kingdom (UK), with more than one-third over the age of 65 years [9]. Malnutrition Attribution (CC BY) license (https:// is not only highly prevalent in hospitals [10], where, at admission, about 30% of patients creativecommons.org/licenses/by/ are at risk of malnutrition [11], but is also frequently present prior to hospital admission in 4.0/). community-dwelling older people living at home or in residential care [12,13]. Detecting Nutrients 2021, 13, 1883. https://doi.org/10.3390/nu13061883 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 1883 2 of 24 malnutrition in the community is therefore of great importance. Health and social care costs associated with the detrimental effects of malnutrition are estimated to be £23.5 billion in the UK, with costs for malnourished patients estimated to be three times higher than for others [14], due to increased visits to primary care, hospital admissions and duration of hospitalisation [8,14]. Malnutrition can be a consequence of inadequate intake of macro- or micronutrients, leading to undernutrition, protein-energy malnutrition (PEM) and/or micronutrient defi- ciency, resulting in recognisable physiological, metabolic and clinical symptoms. Micronu- trient deficiencies alone are recognised as contributing to substantial health consequences in older adults, including frailty and sarcopenia [5,15–22]. Other than an inadequate di- etary intake, impairments in nutrient absorption, transport and utilization, accompanied by clinical conditions, may also contribute to the development of malnutrition that also includes micronutrient deficiency [23]. The physiological consequences of malnutrition in older adults are often difficult to reverse. The detrimental health effects of malnutrition on individuals as well as its significant health and social care costs reinforce the need for early detection and intervention to address malnutrition. However, despite the use of “established malnutrition screening tools” (e.g., Mini Nutritional Assessment (MNA) [24], Subjective Global Assessment (SGA) [25] and Nutritional Risk Screening (NRS 2002) [26]) in community, secondary and residential care settings, malnutrition in older adults is often underdiagnosed until a critical state is reached. Moreover, these tools are used inconsistently, and nutritional intervention or treatment is not always provided [14]. In order to provide a more readily available tool for early malnutrition screening and detection of at-risk free-living individuals in the community, we investigated the potential of blood measurement data from clinical “routine biochemical diagnostic tests” to predict poor nutritional status. Routine biochemical diagnostic tests are readily available from health checks in middle and older aged individuals in primary and secondary care in many healthcare systems in Europe and the United States (US). Since these biochemical tests are performed routinely, whereas malnutrition screening is not, these biochemicals may be useful to alert to the presence of under- or malnutrition. Routinely measured bio- chemical diagnostic tests include measurements of cholesterol, haemoglobin A1C (HbA1c), creatinine and Estimated Glomerular Filtration Rate (eGFR), which are typically used to determine risk and treatment for conditions, such as cardiovascular disease, diabetes or renal failure, and are predictive of morbidity and mortality [27–29]. Certain routinely used biochemical tests have also been shown to be associated with the risk of micronutrient insufficiency [30,31] and with established malnutrition screening tools in a secondary care setting [32]. However, they have not yet been tested in a community setting. To our knowl- edge there are no previous studies that investigated both cut-off points for biochemical tests that are used in clinical practice for alerting clinicians to risk or treatment of disease, alongside cut-off points used for alerting clinicians specifically to risk of malnutrition. Our analysis used data from the National Diet and Nutrition Survey (NDNS), which measures food consumption, nutrient intakes and nutritional status of a representative sample of people living in private households in the UK. The NDNS includes data on “established malnutrition indicators”, i.e., individual components included in established malnutrition screening tools and risk factors for malnutrition (e.g., low protein intake, poor appetite and polypharmacy [33]), but did not administer complete malnutrition screening tools within the survey. Moreover, the NDNS measured “biomarkers of micronutrient deficiency” in blood, which are associated with clinically recognisable symptoms and morbidities, as well as being accepted measures of dietary intake [5,15–22]. The current study therefore investigated whether routine biochemical diagnostic tests that are routinely measured in clinical practice (e.g., HbA1c, cholesterol and eGFR) have the potential to detect and alert clinicians to the presence of an increased risk of malnutrition in free-living individuals of 50 years or older (Figure1). We validated these routine biochemical diagnostic tests firstly against directly measured micronutrient deficiency Nutrients 2021, 13, x FOR PEER REVIEW 3 of 27 Nutrients 2021, 13, 1883 have the potential to detect and alert clinicians to the presence of an increased risk of3 mal- of 24 nutrition in free-living individuals of 50 years or older (Figure 1). We validated these rou- tine biochemical diagnostic tests firstly against directly measured micronutrient defi- biomarkersciency