Trends in glycaemic control and drug use in males and females with type 2 diabetes: Results of the Australian National Diabetes Audit from 2013 to 2019.

AIM: To investigate temporal changes in glycaemic control and the use of antihyperglycaemic therapies in females and males with type 2 diabetes from 2013 to 2019. METHODS: Data from adult patients with type 2 diabetes (n = 11 930; 44.9% females, mean [SD] age of 62.9 [12.9] years) were analysed from the 2013 to 2019 biennial cross-sectional Australian National Diabetes Audit. RESULTS: Mean HbA1c remained similar throughout the years examined and between the sexes (7.8%-8.3%, 62-67 mmol/mol; P > .05). The number of antihyperglycaemic agents used by both sexes increased from 2013 to 2019 (P < .001), with more agents used by males (P = .014). From 2013 to 2019, there were increasing proportions of both sexes using dipeptidyl peptidase-4 inhibitors (females: 11.7%-25.7%, P = .045; males: 11.6%-29.5%, P = .036) and glucagon-like peptide-1 receptor agonists (females: 5.9%-15.3%; males: 4.9%-11.1%; P = .043 for both). Sodium-glucose co-transporter-2 inhibitors were not available in 2013; however, their use increased substantially from 2015 to 2019 in both females (4.9%-26.3%, P = .013) and males (4.7%-32.2%, P = .019). CONCLUSIONS: From 2013 to 2019, mean HbA1c levels remained unchanged despite a concurrent increase in the number of antihyperglycaemic medications used. Overall, there was a trend towards preferencing newer agents with some differences in treatment regimens relating to sex and renal function.

Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans.

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species-in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

Rethinking good cholesterol: a clinicians' guide to understanding HDL.

Low HDL cholesterol dyslipidaemia affects about half of people with type 2 diabetes and represents a major independent risk factor for atherosclerotic cardiovascular disease. The "good cholesterol" label was coined decades ago on the basis of a presumed causal role of HDL cholesterol in atherosclerotic cardiovascular disease. However, this view has been challenged by the negative results of several studies of HDL cholesterol-raising drugs, creating a paradox for clinicians regarding the value of HDL cholesterol as a risk biomarker and therapeutic target, and seemingly contradicting decades of evidence substantiating an inverse relation between HDL cholesterol and cardiovascular disease risk. We seek to resolve this issue by revisiting the history of the HDL hypothesis, chronicling how this paradox is ultimately rooted in the progressive erroneous blurring of the distinction between HDL and HDL cholesterol. We describe the compositional complexity of HDL particles beyond their cholesterol cargo and focus on their role in lipid transport. We discuss the evidence regarding novel HDL functions, including effects on glucose metabolism, and speculate on the implications for type 2 diabetes. HDL cholesterol is an imperfect biomarker of a highly complex and multifunctional lipid transport system, and we should now consider how new HDL markers more causally linked to cardiovascular complications could be adapted for clinical use. In the absence of a superior alternative, HDL cholesterol generally has value as a component of primary cardiovascular disease risk prediction models, including in people with type 2 diabetes. However, to avoid prognostic overgeneralisations, it is high time that the good cholesterol label is dropped.

Brown adipose tissue and lipid metabolism: New strategies for identification of activators and biomarkers with clinical potential.

Development of therapeutic agents directed towards increasing brown adipose tissue (BAT) energy expenditure to combat obesity and its comorbidities is currently an area of intense research. Both preclinical and clinical studies have suggested a potentially significant role for BAT in regulating whole body energy expenditure as well as glucose and lipid metabolism. Lipids, particularly long chain fatty acids (LCFAs), are recognized as integral substrates in mediating the primary heat-producing functions of BAT, and to date thought to be principally sourced from stored intracellular lipid droplets. While this prior understanding is not disputed, recent evidence has demonstrated the importance of lipids derived from the circulation, including those from dietary sources and from tissue lipolysis, especially white adipose tissue lipolysis. Moreover, recent studies have shed further light on a potential role for BAT as an autocrine, paracrine and endocrine organ, with lipids as key signaling molecules. Advances in metabolomics have enabled high-resolution exploration of biomolecules that may be associated with various physiological processes and potentially pathological states. Such approaches have led to several novel lipid species recently being associated with BAT function and dysfunction. Further exploration of the circulating lipidome will likely reveal additional novel BAT biomarkers that can inform development of BAT-directed therapies. This review will address current progress and new strategies to identify and characterize BAT-associated lipids which may represent both novel activators and/or activity biomarkers with both research and clinical utility.