Prediction of metabolic subphenotypes of type 2 diabetes via continuous glucose monitoring and machine learning.

The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them).

Lifestyle Profiling Using Wearables and Prediction of Glucose Metabolism in Individuals with Normoglycemia or Prediabetes.

This study examined the relationship between lifestyles (diet, sleep, and physical activity) and glucose responses at a personal level. 36 healthy adults in the Bay Area were monitored for their lifestyles and glucose levels using wearables and continuous glucose monitoring (NCT03919877). Gold-standard metabolic tests were conducted to phenotype metabolic characteristics.

Predicting Type 2 Diabetes Metabolic Phenotypes Using Continuous Glucose Monitoring and a Machine Learning Framework.

Type 2 diabetes (T2D) and prediabetes are classically defined by the level of fasting glucose or surrogates such as hemoglobin HbA1c. This classification does not take into account the heterogeneity in the pathophysiology of glucose dysregulation, the identification of which could inform targeted approaches to diabetes treatment and prevention and/or predict clinical outcomes. We performed gold-standard metabolic tests in a cohort of individuals with early glucose dysregulation and quantified four distinct metabolic subphenotypes known to contribute to glucose dysregulation and T2D: muscle insulin resistance, β-cell dysfunction, impaired incretin action, and hepatic insulin resistance.

Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans.

Dietary fibers act through the microbiome to improve cardiovascular health and prevent metabolic disorders and cancer. To understand the health benefits of dietary fiber supplementation, we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multiomic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel, and clinical measurements on healthy and insulin-resistant participants.

Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women.

Research has identified reduced circulating 25-hydroxyvitamin D [25(OH)D] in individuals with the rs7041 (c.1296T>G) T allele in the vitamin D binding protein gene ( GC); however, the effects of the T allele on vitamin D biomarkers during pregnancy and lactation are unknown. Thus, we examined the metabolic effects of GC rs7041 on vitamin D biomarkers among third-trimester pregnant ( n = 26), lactating ( n = 28), and nonpregnant/nonlactating ( n = 21) women consuming a single amount of vitamin D (511 IU/d) and related nutrients for 10-12 wk.

Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk.

Maternal vitamin D biomarkers are associated with maternal and fetal bone turnover among pregnant women consuming controlled amounts of vitamin D, calcium, and phosphorus.

Vitamin D plays a central role in calcium homeostasis; however, its relationship with bone turnover during pregnancy remains unclear due to a lack of studies that have rigorously controlled for vitamin D and other nutrients known to influence bone metabolism. Similarly, prior investigations of the effect of pregnancy on bone turnover relative to the nonpregnant state may have been confounded by varying intakes of these nutrients. Nested within a controlled intake study, the present investigation sought to quantify associations between maternal vitamin D biomarkers and biochemical markers of bone turnover among pregnant (versus nonpregnant) women and their fetuses under conditions of equivalent and adequate intakes of vitamin D and related nutrients.

Vitamin D Metabolism Varies among Women in Different Reproductive States Consuming the Same Intakes of Vitamin D and Related Nutrients.

Background: The impact of the reproductive state on vitamin D metabolism and requirements is uncertain in part because of a lack of studies with controlled dietary intakes of vitamin D and related nutrients.

Objective: We aimed to quantify the impact of the reproductive state on a panel of vitamin D biomarkers among women of childbearing age consuming equivalent amounts of vitamin D and related nutrients.

Methods: Nested within a feeding study providing 2 doses of choline, healthy pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant/nonlactating; n = 21) women consumed a single amount of vitamin D (511 ± 48 IU/d: 311 ± 48 IU/d from diet and 200 IU/d as supplemental cholecalciferol) and related nutrients (1.