By Heather Davis, MS, RDN, LDN
Assessing an individual’s risk for prediabetes and, ultimately, type 2 diabetes (T2D), typically involves considering factors such as age, BMI/weight, ethnicity, family history, physical activity levels, and medical history of conditions like dyslipidemia, CVD, obstructive sleep apnea, polycystic ovarian syndrome, and gestational diabetes, among others. But what if there were other more precise methods and markers we could use to capture at-risk populations—especially earlier in life? Early detection is incredibly important for preventing diabetes and its many debilitating complications.
Nearly one in five adolescents and one in four young adults in the United States have prediabetes. Young people with prediabetes have a high T2D risk, and 8% develop young-onset T2D within three years of diagnosis. Lifestyle interventions for individuals with prediabetes can decrease T2D risk by 40% to 70%.1 With interventions involving dietary modification and physical activity acting as the most effective means for addressing these risks, it makes sense to direct efforts at those who are most in need.
Which Metabolites?
Many circulating metabolites have been shown to predict the risk of T2D and can also be impacted by lifestyle interventions. The Human Metabolome Database lists 21 unique plasma metabolites associated with T2D. These include certain amino acids, lipids, and sugar metabolites. For example, increased circulating concentrations of branched chain amino acids and aromatic amino acids have been associated with an increased risk for T2D, while increased levels of glycine, indolepropionic acid and phsophatidylcholines have been associated with a decreased risk. Some research has specifically looked at the impact of intervention studies, where N-acetyl-d-galactosamine, trimethylglycine, methionine sulfoxide, 7-methylguanine, propionylcarnitine, putrescine, and serine have been associated with regression of disease.2
In one longitudinal cohort study published in 2024 in Diabetes Care, researchers examined postprandial metabolite profiles and risk of prediabetes in Hispanic youth and young adults. This was the largest study to date to pinpoint predictive metabolites for risk of prediabetes in adolescents and young adults and the first to focus on Hispanic adolescents—a high-risk and understudied population for T2D. Authors of this study explain that since decreased metabolic flexibility and altered postprandial metabolite profiles may be present years before prediabetes develops, looking at metabolite levels after a glucose challenge may be more informative for prediabetes risk in young people than fasting metabolites.1
Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. Caprylic acid (a fatty acid) and allylphenol sulfate (a phytochemical found in fruits and vegetables), were strong contenders for potential early markers of impaired glucose tolerance (IGT) and elevated HbA1c. Taurocholic acid, a bile acid linked to gut microbiome dysbiosis, was also associated with elevated prediabetes risk in study participants, but may need more clarification in future studies. Predictive models with the two metabolites (caprylic acid and allylphenol sulfate) impressively outperformed models that included established T2D risk factors.1
Another study, coming out of Finland and published in 2025 in Scientific Reports, identified predictive metabolites most responsive to lifestyle intervention with evidence-based targets for nutrition and physical activity in individuals at high risk of T2D. Not only do some of these metabolites hold promise for early prediction of risk but they also are a potential additional tool for evaluating individual response to intervention. A standard oral glucose tolerance test was used to categorize 624 participants into those having normal glucose tolerance, isolated IGT, IGT with increased fasting glucose, and T2D. Fatty acid amides, phospholipids, amino acids, dimethylguanidinovaleric acid, and 5-aminovaleric acid betaine responded most to the lifestyle intervention. Lysophosphatidylcholines containing odd-chain fatty acids showed associations with improved glucose metabolism. Twenty-five metabolites differed between the baseline groups, responded to the intervention, and were associated with changes in glucose metabolism.2
The Finnish study also helps advance the investigation of “metabotypes.” Metabotyping, an emerging potential tool in the personalized nutrition toolbox, seeks to identify distinct groups of individuals with specific biochemical “fingerprints,” including metabolite profiles, that could signal unique responses to the same intervention, such as the same diet. In other words, different metabotypes may have different responses to the same intervention as well as different degrees of disease risk.3
Seeing the Big Picture
It’s always exciting to consider the powerful potential of improved diagnostic tools on the horizon. However, many health care providers, including RDs, may voice concern about how these and other life-changing diagnostics waiting in the wings will be accessible to the people who need them most. Although improvements in early diabetes risk detection and advancements in personalized medicine should be celebrated, one of the biggest barriers to care—having access to earlier and more sensitive diagnostics—comes down to questions of broader health care access and affordability. For vulnerable populations at higher risk for T2D and arguably in greater need of future early detection tools, inability to afford or access even basic care may be an insurmountable hurdle. With changes now taking place across the country concerning health care policy, access, and coverage, many providers are increasingly concerned about new legislation that experts at Johns Hopkins Bloomberg School of Public Health say could leave millions more without health care coverage in the coming decade.4 The majority of the planned budget cuts impact federal support for Medicaid, which helps cover medical costs for low-income families, older adults, and people with disabilities. The changes also alter who is eligible to receive Medicaid and Medicare benefits or access insurance plans—which could increase health care costs for all Americans.4 The American Medical Association points out that these policy changes will also negatively impact Medicare physician payment and medical student loans, all of which will likely worsen patient access to care.5
As key health care providers at the frontline of diabetes prevention and treatment, RDs are central to the fight for equitable care and understand that emerging diagnostics offering promise to patients are only as good as the infrastructure that enables their current and future access.
— Heather Davis, MS, RDN, LDN, editor
References
1. Goodrich JA, Wang H, Walker DI, et al. Postprandial metabolite profiles and risk of prediabetes in young people: a longitudinal multicohort study. Diabetes Care. 2024;47(1):151-159.
2. Koistinen VM, Manninen S, Tuomainen M, et al. Metabolites associated with abnormal glucose metabolism responding to primary care lifestyle intervention. Sci Rep. 2025;15:39093.
3. Palmnäs M, Brunius C, Shi L, et al. Perspective: metabotyping—a potential personalized nutrition strategy for precision prevention of cardiometabolic disease. Advances in Nutrition. 2020;11(3):524-532.
4. Rosen A. How new federal legislation will affect health care costs and access for Americans. Johns Hopkins Bloomberg School of Public Health website. https://publichealth.jhu.edu/2025/the-changes-coming-to-the-aca-medicaid-and-medicare. Published July 30, 2025. Accessed November 11, 2025.
5. Changes to Medicaid, the ACA and other key provisions of the One Big Beautiful Bill Act. American Medical Association website. https://www.ama-assn.org/health-care-advocacy/federal-advocacy/changes-medicaid-aca-and-other-key-provisions-one-big. Updated November 7, 2025. Accessed November 11, 2025.
