Should the last be first? Questions and dilemmas regarding early short-term insulin treatment in Type 2 Diabetes Mellitus.

INTRODUCTION: Early short-term insulin treatment (STIT), defined as insulin administration shortly after diabetes diagnosis for only a brief period of time, is an alternative concept, aiming to entirely revise the perspective of type 2 diabetes (T2DM) management. AREAS COVERED: The present review intends to summarize what is already known regarding early STIT in T2DM and highlight questions and dilemmas from the clinician's point of view, with a discourse on future research agenda. EXPERT OPINION: STIT has the potential to modify the natural history of T2DM, resulting in improved drug-free remission rates by favorably affecting the underlying pathophysiology of the disease. Existing data in the field manifest significant weaknesses, mainly being the small number of trials and patients included, the lack of control groups in most studies and the wide heterogeneity between study designs and explored outcomes, which limit definitive conclusions. Therefore, before such a therapeutic strategy is incorporated into daily practice, important issues require further clarification by future trials. These issues include the optimal time point for the intervention, the ideal insulin type, the identification of patients being most likely to benefit, the STIT effects on cardiovascular and other clinical outcomes and the cost-effectiveness evaluation of this therapeutic strategy. ABBREVIATIONS: T2DM: Type 2 Diabetes Mellitus; HbA1C: Hemoglobin A1c; OHA: Oral Hypoglycemic Agents; STIT: Short-term Insulin Treatment; CSII: Continuous Subcutaneous Insulin Infusion; MDI: Multiple Daily Injections; PPG: Postprandial Plasma Glucose; FPG: Fasting Plasma Glucose; HOMA-b: Homeostasis Model Assessment of beta-cell function; TDD: Total Daily Insulin Dose; DI: Disposition Index; HOMA-IR: Homeostasis Model Assessment of Insulin Resistance; ROS: Reactive Oxygen Species; TNF: Tumor Necrosis Factor; GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent Insulinotropic Polypeptide; BMI: Body Mass Index; CV: Cardiovascular; DR: Diabetic Retinopathy; SU: Sulfonylurea; IGI: Insulinogenic Index.

Lipoprotein(a) in postmenopausal women: assessment of cardiovascular risk and therapeutic options.

INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause"). RESULTS: Only hormone replacement therapy (mainly oral estrogens) and tibolone have been specifically studied in postmenopausal women and can reduce Lp(a) concentrations by up to 44%, although evidence indicating a concomitant reduction in CVD risk associated with Lp(a) is lacking. As alternative treatments for women who cannot, or will not, take hormonal therapies, niacin and the upcoming proprotein convertase subtilisin / kexin type 9 (PCSK-9) inhibitors are effective in reducing Lp(a) concentrations by up to 30%. Statins have minimal or no effect on Lp(a). However, data for these and other promising Lp(a)-lowering therapies including mipomersen, lomitapide, cholesterol-ester-transfer protein inhibitors and eprotirome are derived from studies in the general, mainly high CVD risk, population, and include only subpopulations of postmenopausal women. CONCLUSIONS: Past, present and emerging therapies can reduce Lp(a) concentrations to a varying extent. Overall, it remains to be proven whether the aforementioned reductions in Lp(a) by these therapeutic options are translated into CVD risk reduction in postmenopausal women.