Clinical science
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Randomized Controlled Trial
Breaking up of prolonged sitting over three days sustains, but does not enhance, lowering of postprandial plasma glucose and insulin in overweight and obese adults.
To compare the cumulative (3-day) effect of prolonged sitting on metabolic responses during a mixed meal tolerance test (MTT), with sitting that is regularly interrupted with brief bouts of light-intensity walking. Overweight/obese adults (n=19) were recruited for a randomized, 3-day, outpatient, cross-over trial involving: (1) 7-h days of uninterrupted sitting (SIT); and (2) 7-h days of sitting with light-intensity activity breaks [BREAKS; 2-min of treadmill walking (3.2 km/h) every 20 min (total: 17 breaks/day)]. On days 1 and 3, participants underwent a MTT (75 g of carbohydrate, 50 g of fat) and the incremental area under the curve (iAUC) was calculated from hourly blood samples. ⋯ The insulin iAUC was also higher on both days in SIT (day 1: ∆151 ± 73, day 3: ∆91 ± 73 pmol·h·l(-1), P=0.01), with no effect of time (P=0.52) or time × condition (P=0.71). There was no between-treatment difference in triglycerides (triacylglycerols) iAUC. There were significant between-condition effects but no temporal change in metabolic responses to MTT, indicating that breaking up of sitting over 3 days sustains, but does not enhance, the lowering of postprandial glucose and insulin.
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Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. ⋯ Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established.