No abstract

BACKGROUND Obesity-linked metabolic syndrome (MetS) is associated with a dyslipidemic profile that includes hypertriglyceridemia and low plasma high-density lipoprotein cholesterol (HDL-C). HDL initiates reverse cholesterol transport (RCT) via macrophage cholesterol efflux (MCE). Some hypothesize that dyslipidemic patients have impaired RCT. MCE to patient plasma, a metric of HDL function, inversely correlates with atherosclerotic burden. Paradoxically, MCE to plasma of hypertriglyceridemic subjects is higher than that to normolipidemic (NL) plasma. OBJECTIVE Although weight-loss reduces dyslipidemia, its effect on MCE to the plasma of obese, MetS patients is unknown. Thus, we tested the hypothesis that reducing dyslipidemia with weight-loss reduces the MCE capacity of MetS plasma to that of NL plasma. METHODS Cholesterol efflux (MCE) from THP-1 macrophages to plasma from NL controls and to obese, MetS patients before and after weight-loss was measured. RESULTS MCE to plasma of obese, MetS patients was higher than that to control plasma (p=0.006). Weight-loss in MetS patients (mean = −9.77 kg) reduced dyslipidemia, insulin resistance and systolic blood pressure. HDL-C was unchanged and apolipoprotein A-I decreased with weight-loss. Weight-loss in MetS patients normalized MCE (p<0.001) to that of NL subjects. MCE correlated with apolipoprotein B levels (r2 = 0.13 – 0.38). Chromatography showed that macrophage cholesterol initially associates with HDL but accumulates in apolipoprotein B-containing lipoproteins at later times. CONCLUSIONS While the initial acceptor of macrophage cholesterol efflux is HDL, the elevated apo B lipoproteins are a cholesterol sink that increase MCE in MetS patients. Weight loss results in decreased apo B-lipoproteins and decreased MCE to plasma of MetS patients.

No abstract

OBJECTIVE Continuous glucose monitoring (CGM) parameters may identify individuals at risk for progression to overt type 1 diabetes. We aimed to determine whether CGM metrics provide additional insights into progression to clinical stage 3 type 1 diabetes. RESEARCH DESIGN AND METHODS One hundred five relatives of individuals in type 1 diabetes probands (median age 16.8 years; 89% non-Hispanic White; 43.8% female) from the TrialNet Pathway to Prevention study underwent 7-day CGM assessments and oral glucose tolerance tests (OGTTs) at 6-month intervals. The baseline data are reported here. Three groups were evaluated: individuals with 1) stage 2 type 1 diabetes (n = 42) with ≥2 diabetes-related autoantibodies and abnormal OGTT; 2) stage 1 type 1 diabetes (n = 53) with ≥2 diabetes-related autoantibodies and normal OGTT; and 3) negative test for all diabetes-related autoantibodies and normal OGTT (n = 10). RESULTS Multiple CGM metrics were associated with progression to stage 3 type 1 diabetes. Specifically, spending ≥5% time with glucose levels ≥140 mg/dL (P = 0.01), ≥8% time with glucose levels ≥140 mg/dL (P = 0.02), ≥5% time with glucose levels ≥160 mg/dL (P = 0.0001), and ≥8% time with glucose levels ≥160 mg/dL (P = 0.02) were all associated with progression to stage 3 disease. Stage 2 participants and those who progressed to stage 3 also exhibited higher mean daytime glucose values; spent more time with glucose values over 120, 140, and 160 mg/dL; and had greater variability. CONCLUSIONS CGM could aid in the identification of individuals, including those with a normal OGTT, who are likely to rapidly progress to stage 3 type 1 diabetes.