Diet and Meal Pattern Determinants of Glucose Levels and Variability in Adults with and without Prediabetes or Early-Onset Type 2 Diabetes: A Pilot Study.

This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (ß = -2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (ß = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (ß = 0.9, SE = 0.4, p = 0.02) and GV (ß = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.

Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

Time-restricted eating to improve cardiometabolic health: The New York Time-Restricted EATing randomized clinical trial - Protocol overview.

Re-aligning eating patterns with biological rhythm can reduce the burden of metabolic syndrome in older adults with overweight or obesity. Time-restricted eating (TRE) has been shown to result in weight loss and improved cardiometabolic health while being less challenging than counting calories. The New York Time-Restricted EATing study (NY-TREAT) is a two-arm, randomized clinical trial (RCT) that aims to examine the efficacy and sustainability of TRE (eating window ≤10 h/day) vs. a habitual prolonged eating window (HABIT, ≥14 h/day) in metabolically unhealthy midlife adults (50-75 years) with overweight or obesity and prediabetes or type 2 diabetes (T2D). Our primary hypothesis is that the TRE will result in greater weight loss compared to HABIT at 3 months. The efficacy of the TRE intervention on body weight, fat mass, energy expenditure, and glucose is tested at 3 months, and the sustainability of its effect is measured at 12 months, with ambulatory assessments of sleep and physical activity (ActiGraph), eating pattern (smartphone application), and interstitial glucose (continuous glucose monitoring). The RCT also includes state-of-the-art measurements of body fat (quantitative magnetic resonance), total energy expenditure (doubly-labelled water), insulin secretion, insulin resistance, and glucose tolerance. Adherence to self-monitoring and reduced eating window are monitored remotely in real-time. This RCT will provide further insight into the effects of TRE on cardiometabolic health in individuals with high metabolic risk. Sixty-two participants will be enrolled, and with estimated 30% attrition, 42 participants will return at 12 months. This protocol describes the design, interventions, methods, and expected outcomes. Clinical trial registration:NCT04465721 IRB: AAAS7791.

Nonalcohol fatty liver disease: balancing supply and utilization of triglycerides.

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is defined as the abnormal accumulation of lipids in the liver, called hepatic steatosis, which occurs most often as a concomitant of the metabolic syndrome. Its incidence has surged significantly in recent decades concomitant with the obesity pandemic and increasing consumption of refined carbohydrates and saturated fats. This makes a review of the origins of NAFLD timely and relevant. RECENT FINDINGS: This disorder, which shares histologic markers found in alcoholic fatty liver disease, was named NAFLD to distinguish it from the latter. Recently, however, the term metabolic-associated fatty liver disease (MAFLD) has been suggested as a refinement of NAFLD that should highlight the central, etiologic role of insulin resistance, obesity, and diabetes mellitus. The complexity of the pathways involved in the regulation of hepatic triglyceride synthesis and utilization have become obvious over the past 10 years, including the recent identification of monogenic causes of metabolic-associated fatty liver disease. These include PNPLA3, transmembrane 6 superfamily member 2, GCKR, membrane-bound O-acyltransferase 7 suggest targets for new therapies for hepatic steatosis. SUMMARY: The current review can serve as a guide to the complex pathways involved in the maintenance of hepatic triglyceride levels as well as an introduction to the most recent discoveries, including those of key genes that have provided opportunities for new and novel therapeutics.

Hypertriglyceridemia-Causes, Significance, and Approaches to Therapy.

Hypertriglyceridemia (HTG) is a common metabolic disorder with both genetic and lifestyle factors playing significant roles in its pathophysiology. HTG poses a risk for the development of cardiovascular disease (CVD) in the population at large and for pancreatitis in about two percent of individuals with extremely high levels of triglycerides (TG). This manuscript summarizes the mechanisms underlying the development of HTG as well as its management, including emerging therapies targeted at specific molecular pathways.