The classification of diabetes and prediabetes by static glucose thresholds obscures the pathophysiological dysglycemia heterogeneity, primarily driven by insulin resistance (IR), beta-cell dysfunction, and incretin deficiency. This review demonstrates that continuous glucose monitoring and wearable technologies enable a paradigm shift towards non-invasive, dynamic metabolic phenotyping. We show evidence that machine learning models can leverage high-resolution glucose data from at-home, CGM-enabled oral glucose tolerance tests to accurately predict gold-standard measures of muscle IR and beta-cell function. This personalized characterization extends to real-world nutrition, where an individual's unique postprandial glycemic response (PPGR) to standardized meals, such as the relative glucose spike to potatoes versus grapes, could serve as a biomarker for their metabolic subtype. Moreover, integrating wearable data reveals that habitual diet, sleep, and physical activity patterns, particularly their timing, are uniquely associated with specific metabolic dysfunctions, informing precision lifestyle interventions. The efficacy of dietary mitigators in attenuating PPGR is also shown to be phenotype-dependent. Collectively, this evidence demonstrates that CGM can deconstruct the complexity of early dysglycemia into distinct, actionable subphenotypes. This approach moves beyond simple glycemic control, paving the way for targeted nutritional, behavioral, and pharmacological strategies tailored to an individual's core metabolic defects, thereby paving the way for a new era of precision diabetes prevention.

This study evaluates causal reasoning in large language models (LLMs) using 99 clinically grounded laboratory test scenarios aligned with Pearl's Ladder of Causation: association, intervention, and counterfactual reasoning. We examined common laboratory tests such as hemoglobin A1c, creatinine, and vitamin D, and paired them with relevant causal factors including age, gender, obesity, and smoking. Two LLMs - GPT-o1 and Llama-3.2-8b-instruct - were tested, with responses evaluated by four medically trained human experts. GPT-o1 demonstrated stronger discriminative performance (AUROC overall = 0.80 +/- 0.12) compared to Llama-3.2-8b-instruct (0.73 +/- 0.15), with higher scores across association (0.75 vs 0.72), intervention (0.84 vs 0.70), and counterfactual reasoning (0.84 vs 0.69). Sensitivity (0.90 vs 0.84) and specificity (0.93 vs 0.80) were also greater for GPT-o1, with reasoning ratings showing similar trends. Both models performed best on intervention questions and worst on counterfactuals, particularly in altered outcome scenarios. These findings suggest GPT-o1 provides more consistent causal reasoning, but refinement is required before adoption in high-stakes clinical applications.

Insulin resistance, a precursor to type 2 diabetes, is characterized by impaired insulin action in tissues. Current methods for measuring insulin resistance, while effective, are expensive, inaccessible, not widely available and hinder opportunities for early intervention. In this study, we remotely recruited the largest dataset to date across the US to study insulin resistance (N=1,165 participants, with median BMI=28 kg/m2, age=45 years, HbA1c=5.4%), incorporating wearable device time series data and blood biomarkers, including the ground-truth measure of insulin resistance, homeostatic model assessment for insulin resistance (HOMA-IR). We developed deep neural network models to predict insulin resistance based on readily available digital and blood biomarkers. Our results show that our models can predict insulin resistance by combining both wearable data and readily available blood biomarkers better than either of the two data sources separately (R2=0.5, auROC=0.80, Sensitivity=76%, and specificity 84%). The model showed 93% sensitivity and 95% adjusted specificity in obese and sedentary participants, a subpopulation most vulnerable to developing type 2 diabetes and who could benefit most from early intervention. Rigorous evaluation of model performance, including interpretability, and robustness, facilitates generalizability across larger cohorts, which is demonstrated by reproducing the prediction performance on an independent validation cohort (N=72 participants). Additionally, we demonstrated how the predicted insulin resistance can be integrated into a large language model agent to help understand and contextualize HOMA-IR values, facilitating interpretation and safe personalized recommendations. This work offers the potential for early detection of people at risk of type 2 diabetes and thereby facilitate earlier implementation of preventative strategies.

Insulin resistance (IR) is a key precursor to diabetes and a significant risk factor for cardiovascular disease. Traditional IR assessment methods require multiple blood tests. We developed a simple AI model using only fasting blood glucose to predict IR in non-diabetic populations. Data from the NHANES (1999-2020) and CHARLS (2015) studies were used for model training and validation. Input features included age, gender, height, weight, blood pressure, waist circumference, and fasting blood glucose. The CatBoost algorithm achieved AUC values of 0.8596 (HOMA-IR) and 0.7777 (TyG index) in NHANES, with an external AUC of 0.7442 for TyG. For METS-IR prediction, the model achieved AUC values of 0.9731 (internal) and 0.9591 (external), with RMSE values of 3.2643 (internal) and 3.057 (external). SHAP analysis highlighted waist circumference as a key predictor of IR. This AI model offers a minimally invasive and effective tool for IR prediction, supporting early diabetes and cardiovascular disease prevention.

Can a strawberry a day keep dementia away? A study published in the journal Nutrients last month suggests that could be possible. Researchers from the University of Cincinnati (UC) studied a total of 30 patients between 50 and 65 years of age who had experienced symptoms of mild cognitive decline. The participants were told to avoid eating any berry fruit -- and instead added a packet of supplement powder to their water each morning, according to a press release from UC. For half the group, the powder contained strawberries.

Machine learning shows remarkable success for recognizing patterns in data. Here we apply the machine learning (ML) for the diagnosis of early stage diabetes, which is known as a challenging task in medicine. Blood glucose levels are tightly regulated by two counter-regulatory hormones, insulin and glucagon, and the failure of the glucose homeostasis leads to the common metabolic disease, diabetes mellitus. It is a chronic disease that has a long latent period the complicates detection of the disease at an early stage. The vast majority of diabetics result from that diminished effectiveness of insulin action. The insulin resistance must modify the temporal profile of blood glucose. Thus we propose to use ML to detect the subtle change in the temporal pattern of glucose concentration. Time series data of blood glucose with sufficient resolution is currently unavailable, so we confirm the proposal using synthetic data of glucose profiles produced by a biophysical model that considers the glucose regulation and hormone action. Multi-layered perceptrons, convolutional neural networks, and recurrent neural networks all identified the degree of insulin resistance with high accuracy above $85\%$.

For many years, diabetes cases have largely been classified as either type 1 or type 2. But a new study suggests that there may actually be five different types of the disease--some of which may be more dangerous than others. A new classification system could help doctors identify the people most at risk for complications, the study authors say, and could pave the way for more personalized and effective treatments. The research article, published in The Lancet: Diabetes & Endocrinology, calls attention to the need for an updated diabetes classification system. The current system "has not been much updated during the past 20 years," the authors wrote in their paper, "and very few attempts have been made to explore heterogeneity of type 2 diabetes"--despite calls from expert groups over the years to do so. Meanwhile, they wrote, diabetes is the fastest-increasing disease worldwide, and existing treatments have been unable to stem the tide or prevent the development of chronic complications in many patients.

A team of scientists in the United Kingdom and the U.S. recently reported the discovery of pathological signs of Alzheimer's disease in dolphins, animals whose brains are similar in many ways to those of humans. This is the first time that these signs – neurofibrillary tangles and two kinds of protein clusters called plaques – have been discovered together in marine mammals. As neuroscience researchers, we believe this discovery has added significance because of the similarities between dolphin brains and human brains. The new finding in dolphins supports the research team's hypothesis that two factors conspire to raise the risk of developing Alzheimer's disease in dolphins. Those factors are: longevity with a long post-fertility life span – that is, a species living, on average, many years after the child-bearing years are over – and insulin signaling.

How stress works in the human body, to make or break us -- aeon.co Lots of research on how to manage stress which not surprisingly includes exercise but also highlights how certain stress in our lives can impact us forever. "Adverse early life experience involving poverty, abuse and neglect affects how genes are expressed, and determines how well brain regions such as the hippocampus, amygdala and prefrontal cortex develop and function during childhood into young adulthood. Indeed, the brain is continually changing with experience, which creates memories and alters brain architecture via mechanisms that are facilitated in part by circulating sex, stress and metabolic hormones and chemicals produced by the immune system. These insights have led to a new view of epigenetic changes over the life course."