Stümvoll, Michael

Abstract Aims We explored the manifestations of individual weight loss (WL) response to long-term lifestyle interventions on cardiometabolic risk. Methods and results We pooled data from three large long-term lifestyle WL-intervention trials: 24-month DIRECT (ClinicalTrials.gov: NCT00160108; n = 322; 87% adherence), 18-month CENTRAL (ClinicalTrials.gov: NCT01530724; n = 278; 86% adherence), and 18-month DIRECT PLUS (ClinicalTrials.gov: NCT03020186; n = 294; 89% adherence). We analyzed longitudinal changes in cardiometabolic risk markers, including anthropometrics, blood biomarkers, and magnetic-resonance-imaging-assessed fat depots, and measured DNA-methylation, proteomics, and metabolomics. Among trial completers (n = 761, mean age = 50.4 years; 89% men, baseline body-mass-index = 30.1 kg/m2), mean WL was −3.3 kg (−3.5%). We classified participants as Successful-WL (36%) with relative-WL > 5%, WL-Resistant (28%) who did not lose or gained weight, and Moderate-WL (36%) with WL between 0% and 5%. Successful-WL achieved the greatest improvements in multiple health indicators. However, the WL-Resistant also showed some significant improvements, with increased high-density-lipoprotein-cholesterol (HDLc) and decreased leptin and visceral fat (P < 0.05 vs. baseline). Overall, each 1 kg sustained lifestyle-induced WL was associated with improvements in lipid markers and insulin resistance [HDLc (+1.44%), triglycerides (−1.37%), insulin (−2.46%), HOMA-IR (−2.71%), leptin (−2.79%)] and intrahepatic-fat regression (−0.49 absolute-units)] and modest but significant change in systolic and diastolic blood pressures (−0.26% and −0.36%). We identified 12 significant methylation sites that are associated with Successful-WL (FDR < 0.05; AUC = 0.73). Conclusion While only ∼one-third of individuals achieved long-term WL, the Moderate-WL and WL-Resistant individuals could benefit improvements in visceral adiposity and cardiometabolic risk by shifting towards a healthy lifestyle pattern, beyond WL. Site-specific DNA methylation may predict an individual's likelihood of successful WL. Registration NCT00160108, NCT01530724, NCT03020186.

Abstract Aim To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). Methods In a 4‐week, randomized crossover‐controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%‐8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw‐fresh‐aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4‐day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. Results Forty patients (adherence rate = 88.5%; 743 person‐intervention‐days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two‐thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P < .001) and delayed the time‐to‐peak by 20.0% (112.5 [interquartile range: 75‐135] vs. 90 [60‐105] min; P < .001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P < .001; decline slope: −6.1 vs. water: −7.9 mg/[dL h]; P < .01). Mean postprandial net incremental area‐under‐the‐glucose‐curve was lowered by 20.1% with Mankai compared with water ( P = .03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high‐density lipoprotein cholesterol ratio in the Mankai group (−0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P = .05). Conclusions Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case‐study evidence for plant‐based treatments in T2D to complement a healthy lifestyle and pharmacotherapy.