Publications by authors named "Michael Cobble"

Background: Elevated postprandial triglycerides reflect a proatherogenic milieu, but underlying mechanisms are unclear.

Objective: We examined differences between fasting and nonfasting profiles of directly measured lipoprotein size and subfractions to assess if postprandial triglycerides reflected increases in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and remnants, or small dense lipid depleted LDL (sdLDL) particles.

Methods: We conducted a cross-sectional analysis of 15,397 participants (10,135 fasting; 5262 nonfasting [<8 hours since last meal]) from the VITamin D and OmegA-3 TriaL.

View Article and Find Full Text PDF

Background: The VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors.

Methods: Baseline 25(OH)D was measured in 15,804 participants (mean age 68 years.

View Article and Find Full Text PDF

Background: To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes.

Results: The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.

View Article and Find Full Text PDF
Article Synopsis
  • This review analyzes three major SGLT2 inhibitor trials (DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME) and their varied cardiovascular event results.
  • DECLARE-TIMI 58 had the lowest rates of adverse cardiac events and a higher average kidney function (eGFR), which may explain its different outcomes compared to the other trials.
  • The review suggests that future studies should standardize criteria for patient selection and endpoints to make fair comparisons among SGLT2 inhibitors.
View Article and Find Full Text PDF

Context: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain.

Objective: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease (CVD).

Design: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by ANCOVA for thyroid categories or TSH quintiles on a Women's Health Study subcohort.

View Article and Find Full Text PDF

This review aims to explain risk factors, consequences, and management strategies recommended for patients with hypertriglyceridemia. A search of PubMed was performed: 'Hypertriglyceridemia'[Majr], limited to English-language and published in the 5 years up to April 2016. Abstracts of the 680 results were screened for inclusion.

View Article and Find Full Text PDF

Coronary heart disease results in a worse prognosis following a primary event in women than in men, thus demonstrating the critical importance of primary prevention in at-risk individuals beginning early in adulthood. A medical history, physical examination, laboratory determination of lipid and HbA1c levels, as well as assessment of psychosocial factors, including tobacco use, provide a good initial estimate of cardiovascular risk in women. Women with coronary ischemia often present atypically, without dramatic chest pain, but with more subtle symptoms.

View Article and Find Full Text PDF

Background: Cyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials.

View Article and Find Full Text PDF

Elimination of key risk factors such as dyslipidemia and hypertension is important for reducing cardiovascular events later in life. A medical history, physical examination, and laboratory determination of lipid and glycosylated hemoglobin levels provide a good assessment of cardiovascular risk. A statin is first-line therapy for reducing LDL-C, which is the primary lipid target in most patients.

View Article and Find Full Text PDF

The glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have become important options for the management of patients with type 2 diabetes mellitus. While the GLP-1R agonists and DPP-4 inhibitors act on the incretin system to regulate glucose homeostasis, there are important clinical differences among the five agents currently available in the U.S.

View Article and Find Full Text PDF

Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular (CV) disease; however, conclusive evidence that glycemic control leads to improved cardiovascular outcomes is lacking. Saxagliptin is a potent, selective dipeptidyl peptidase-4 inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Saxagliptin was evaluated in a series of phase III trials as monotherapy; add-on therapy to metformin, a sulfonylurea, or a thiazolidinedione; and as initial therapy in combination with metformin.

View Article and Find Full Text PDF

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression.

View Article and Find Full Text PDF

The multifactorial nature of the pathogenesis of T2DM provides an opportunity to combine treatments that act upon different mechanisms. In addition to improving insulin resistance and pancreatic β-cell dysfunction, the GLP-1 agonists and DPP-4 inhibitors improve the impaired incretin response, as well as increase insulin secretion and reduce glucagon secretion, both in a glucose-dependent manner. As a result of these multiple actions, the GLP-1 agonists and DPP-4 inhibitors lower both fasting and postprandial glucose levels.

View Article and Find Full Text PDF

The "treat to target" approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control. Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors. The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options.

View Article and Find Full Text PDF

Working closely with patients and providing ongoing education, ideally in conjunction with a diabetes care team, can help ensure that the best treatment options are selected for an individual patient and that the patient is capable of effective self-management.

View Article and Find Full Text PDF

The overall safety profiles of GLP-1 agonists and DPP-4 inhibitors are favorable, with a low incidence of hypoglycemia. This attribute, along with their weight and cardiovascular benefits, particularly with the GLP-1 agonists, make them appropriate choices in our 3 patient cases. Ongoing safety investigations with GLP-1 agonists and DPP-4 inhibitors will provide further clarity to the complete safety profiles of these agents.

View Article and Find Full Text PDF

Extensive experience from randomized clinical trials demonstrates the efficacy of GLP-1 agonists and DPP-4 inhibitors as monotherapy and in combination with metformin and other agents, although reductions in FPG and PPG, and consequently A1C, are greater with GLP-1 agonists than with DPP-4 inhibitors. This difference may result from the pharmacologic levels of GLP-1 activity that are achieved with the GLP-1 agonists and their direct action on the GLP-1 receptor. The GLP-1 agonists have attributes that would make either of them an appropriate choice in the management of all 3 patients in our case studies, while either DPP-4 inhibitor would be an appropriate choice for Case 1.

View Article and Find Full Text PDF

Heart disease is the primary cause of death in the United States. Fortunately, intervention measures can reduce the risk of cardiovascular disease (CVD) after a patient has been accurately assessed. Atherosclerotic disease, one of the driving forces behind CVD, is not always detected by traditional risk assessment.

View Article and Find Full Text PDF

According to the most recent data from the Centers for Disease Control, nearly 24 million Americans have type 2 diabetes mellitus (T2DM); of these, 6 million individuals with T2DM remain undiagnosed. At least 57 million more American adults are at high risk for developing T2DM by virtue of having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both, which constitute prediabetes. Treating T2DM remains challenging, despite the availability of effective therapies.

View Article and Find Full Text PDF

With the exception of insulin, all diabetes medications have limited glucose-lowering capacity. Therefore, as type 2 diabetes progresses, insulin is often needed to achieve near-normal glycemic targets and avoid complications. Concerns about the initiation of insulin by both clinicians and patients play a major role in poor glycemic control.

View Article and Find Full Text PDF

The roles of glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are rapidly evolving, despite limited recommendations on their use in current guidelines. This evolution is based on data from the large number of clinical trials demonstrating the clinical efficacy and favorable safety profile of these agents in individuals with type 2 diabetes mellitus (T2DM). This article focuses on factors to consider when implementing the GLP-1 receptor agonists and DPP-4 inhibitors as monotherapy or in combination with other agents in the treatment of T2DM.

View Article and Find Full Text PDF