In Focus
Research in brief APOC3 and lipid metabolism
Results from a new study suggest that a marker of reverse cholesterol transport is inversely related to the incidence of cardiovascular events. Researchers used data for HDL cholesterol efflux capacity for 2924 individuals at baseline from the population-based Dallas Heart Study cohort, and followed up participants for a median of 9·4 years, during which 132 individuals had a cardiovascular event. Cholesterol efflux capacity was not related to many markers of cardiovascular risk, including high-sensitivity C-reactive protein, hypertension, diabetes, and smoking. However, higher quartiles of cholesterol efflux capacity were associated with a lower risk of cardiovascular events, even after adjustments for traditional cardiovascular risk factors, HDL cholesterol level, and HDL particle concentration (hazard ratio [HR] for fourth vs first quartile: 0·33, 95% CI 0·19–0·55).
A small study provides some insight into the pathophysiology of the autosomal recessive, familial chylomicronemia syndrome, a disorder typified by insufficient functional liproprotein lipase activity. In an open-label study researchers investigated the effect of ISIS 304801, an inhibitor of apolipoprotein C-III (APOC3) mRNA, given for 85 days, in three individuals with familial chylomicronemia syndrome. APOC3 affects lipid regulation through lipoprotein lipase dependent and— possibly—independent mechanisms. Triglyceride concentrations fell from 15·9, 23·5, and 23·1 mmol/L at baseline to 7·0, 3·3, and 8·3 mmol/L at follow-up. Triglyceride concentration was associated with APOC3 concentration (r=0·866, p<0·001).
Thyroid function and adverse outcomes Results from a new study challenge the appropriateness of present cutoffs for reference ranges for thyroid function tests in people aged 65 years and older. Using data from the US Cardiovascular Health Study cohort, researchers examined incidence of adverse outcomes for 2843 people aged 65 years or older with thyroid function test results in the euthyroid range. During follow-up, higher concentrations of free T4 were associated with increased risk of atrial fibrillation (adjusted HR for a one unit increase in free T4: 1·04, 95% CI 1·01–1·08; p=0·02), heart failure (1·04, 1·00–1·07; p=0·03), and composite cardiovascular disease (1·03, 1·00–1·06; p=0·02). Thyroid-stimulating hormone (TSH) concentration was negatively associated with composite cardiovascular disease (adjusted HR for a one unit increase in TSH: 0·94, 0·88–1·00; p=0·04).
Type 2 diabetes and hip fracture risk People with type 2 diabetes might have a 20% higher risk of hip fracture than their unaffected counterparts, even at early stages of disease, suggest authors of a new study. Using data from a population based cohort study, researchers compared the rate of hip fracture incidence in people with newly diagnosed type 2 diabetes (n=58 483) and matched controls (n=113 448) followed up for a median of 2·63 years. The incidence rate of hip fracture in people with type 2 diabetes was 2·7 per 1000 person-years versus 2·4 per 1000 person-years in controls. The sub-hazard ratio was 1·20 (95% CI 1·06–1·35) after adjustments for potential confounders, including oral corticosteroids, history of fracture, and BMI. Analysis suggested that some of the increase in risk of hip fracture could be due to the presence of other disorders that disproportionately affect people with type 2 diabetes, including chronic kidney disease and cardiovascular disease.
www.thelancet.com/diabetes-endocrinology Vol 3 February 2015
Screening for congenital adrenal hyperplasia The benefits of health-care professionals screening neonates for congenital adrenal hyperplasia are shown in research from the New Zealand Newborn Metabolic Screening Programme, which spans 20 years and has included 1 175 973 newborn babies. 28 female neonates and 16 male neonates were diagnosed with congenital adrenal hyperplasia between 1994 and 2013, resulting in a rate of 2·2 cases per annum. 21 of 44 cases were identified through screening alone, with tests occurring at a mean age of 3·3 (SD 1·4) days, and treatment started at 12 (SD 6·7) days. 23 of 44 cases were suspected clinically in advance of screening results; these neonates were all identified as having abnormal virilisation, were mainly female (n=22), and were treated earlier than neonates identified through screening alone (p <0·0001).
Rituximab in Graves’ orbitopathy The role of β-cell depletion in management of Graves’ orbitopathy is shown in a randomised trial. The study included euthyroid adults with moderate-to-severe Graves’ orbitopathy who were randomly assigned to intravenous methylprednisolone every week for 12 weeks (cumulative dose of 7·5 mg) or rituximab (two 1000 mg doses or one 500 mg dose after protocol amendment). The study was terminated early because of the occurrence of disease reactivation in 5 of 16 individuals in the methylprednisolone group. The primary endpoint of disease inactivation was significantly different between the rituximab and methylprednisolone groups (100% [15/15] vs 68·7% [11/16]; p=0·043).
Dr Mark J Winter/Science Photo Library
HDL cholesterol efflux capacity
Published Online January 15, 2015 http://dx.doi.org/10.1016/ S2213-8587(14)70199-8 For more on HDL cholesterol efflux capacity see N Engl J Med 2014; published online Nov 18. http://dx.doi.org/10.1056/ NEJMoa1409065 For more on thyroid function and adverse outcomes see J Clin Endocrinol Metab 2014; published online Dec 16. http://dx.doi.org/10.1210/ jc.2014-3586 For more on APOC3 and lipid metabolism see N Engl J Med 2014; published online Dec 4. http://dx.doi.org/10.1056/ NEJMoa1400284 For more on type 2 diabetes and hip fracture risk see Osteoporos Int 2014; published online Dec 9. http://dx.doi. org/10.1007/s00198-0142986-9 For more on screening for congenital adrenal hyperplasia see J Clin Endocrinol Metab 2014; published online Dec 12. http:// dx.doi.org/10.1210/jc.20143168 For more on rituximab in Graves’ orbitopathy see J Clin Endocrinol Metab 2014; published online Dec 15. http://dx.doi.org/10.1210/ jc.2014-3014
Seema Kang 101