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Tag: type 2 diabetes

Finding Common Ground for Glycated Haemoglobin Test Targets

In March of this year, the American College of Physicians (ACP) issued a guidance statement on HbA1c targets for adults with type 2 diabetes (T2D), which have been the subject of debates and discussions in the medical community. At the center of this debate is ACP’s recommendation for a target HbA1c goal between 7-8% to maintain optimal glucose control, which is higher than what’s recommended by the American Diabetes Association (ADA) or the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE).

ADA recommends a goal of <7% for HbA1c, even advocating more stringent goals (such as <6.5%) for certain patients with a low risk of hypoglycemia. The AACE/ACE guidelines recommend keeping glycated hemoglobin levels at ≤ 6.5% for most patients with low-risk of side effects.

The statement from ACP also recommends the individualization of T2D therapy, deintensification of therapy for patients that achieve HbA1c levels of less than 6.5%, and controlling symptoms rather than focusing on specific HbA1c goals in patients with a life expectancy of less than 10 years (such as patients aged 80 or older, that reside in a nursing home, or with chronic conditions – including dementia, cancer, end-stage kidney disease, severe COPD, or congestive heart failure). One of the main ideas behind this statement is to balance the benefits of lowering blood glucose with potential risks, such as important side effects (like hypoglycemia and weight gain), costs, and overall patient burden.

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Inflammation and risk of T2DM: Insights from the CANTOS trial

Data from several studies have suggested that persistent low-grade inflammation has an important role in the pathophysiology of many cardiometabolic conditions. Inflammatory markers, such as interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) have been associated with increased risk of cardiovascular adverse events, as well as insulin resistance and hyperglycemia. Canakinumab is a human monoclonal antibody that targets interleukin-1 (IL-1), which is upstream of IL-6 and hs-CRP, thereby decreasing IL-1 signaling and consequent inflammation. Last year, the authors of the CANTOS trial demonstrated that treatment with canakinumab led to the reduction of cardiovascular events independent of lipid levels in patients with prior myocardial infarction and high levels of hs-CRP (≥2 mg/L). The results of this landmark trial served as important proof-of-concept to support the inflammation hypothesis in the pathophysiology of atherothrombosis.

Because inflammation has been shown to play a role in insulin resistance, defective insulin secretion, and the development of type 2 diabetes in pre-clinical experiments and observational studies, authors of the CANTOS trial also tested the hypothesis that canakinumab treatment reduces the risk of incident type 2 diabetes (T2D). A key secondary endpoint of the CANTOS trial was to assess the effect of canakinumab in reducing the progression of prediabetes to diabetes by measuring the rates of new-onset T2D in prediabetic patients. To do so, the trial enrolled a total of 10,061 patients, out of which 4,057 (40.3%) had baseline diabetes, 4,960 (49.3%) had pre-diabetes, and 1,044 (10.4%) were normoglycemic. Results from this highly anticipated study were recently published in the Journal of the American College of Cardiology by Everett and colleagues.

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