Differentiating Familial Chylomicronemia Syndrome From Multifactorial Severe Hypertriglyceridemia by Clinical Profiles.

Context: Differentiation between familial chylomicronemia syndrome (FCS, type 1 hyperlipoproteinemia), a rare metabolic disorder, and the more common multifactorial severe hypertriglyceridemia (sHTG, type 5 hyperlipoproteinemia) is challenging because of their overlapping symptoms but important in patient management.

Objective: To assess whether readily obtainable clinical information beyond triglycerides can effectively diagnose and differentiate patients with FCS from those with sHTG, based on well-curated data from two intervention studies of these conditions.

Methods: The analysis included 154 patients from two phase 3 clinical trials of patients with sHTG, one cohort with genetically confirmed FCS (n = 49) and one with multifactorial sHTG (n = 105).

Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome.

Background: Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels.

Achievement of Target A1C <7.0% (<53 mmol/mol) by U.S. Type 2 Diabetes Patients Treated With Basal Insulin in Both Randomized Controlled Trials and Clinical Practice.

Objective: Many patients with type 2 diabetes do not reach glycemic goals despite basal insulin treatment. This study assessed the achievement of a target A1C <7.0% (<53 mmol/mol) after initiation of basal insulin in two settings.

Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study.

Background: Familial chylomicronemia syndrome (FCS) is a rare metabolic disorder caused by mutations in lipoprotein lipase (LPL) or genes required for LPL functionality and is characterized by hyperchylomicronemia that results in recurrent episodes of acute pancreatitis. Owing to the rarity of FCS, there are few case series describing the phenotypic variability in FCS patients in detail.

Objective: To provide baseline characteristics in the largest study population to date of patients with FCS.

Antisense Inhibition of Protein Tyrosine Phosphatase 1B With IONIS-PTP-1B Improves Insulin Sensitivity and Reduces Weight in Overweight Patients With Type 2 Diabetes.

Objective: To evaluate safety and efficacy of IONIS-PTP-1B, a second-generation 2'--methoxyethyl antisense inhibitor of protein tyrosine phosphatase 1B, as add-on therapy in overweight patients with type 2 diabetes inadequately controlled with metformin with or without sulfonylurea therapy.

Research Design And Methods: In this phase II, double-blind, randomized, placebo-controlled, multicenter trial, overweight and obese patients (BMI ≥27 kg/m) with type 2 diabetes (HbA ≥7.5% [58 mmol/mol] and ≤10.

Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.

Background: Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins.

Methods: We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1.

Lixisenatide reduces glycaemic variability in insulin-treated patients with type 2 diabetes.

Chronic hyperglycaemia and glucose variability are associated with the development of chronic diabetes-related complications. We conducted a pooled analysis of patient-level data from three 24-week, randomized, phase III clinical trials to evaluate the impact of lixisenatide (LIXI) on glycaemic variability (GV) vs placebo as add-on to basal insulin. The main outcome GV measures were standard deviation (s.

Are patients on basal insulin attaining glycemic targets? Characteristics and goal achievement of patients with type 2 diabetes mellitus treated with basal insulin and physician-perceived barriers to achieving glycemic targets.

Aims: To investigate treatment patterns and achievement of glycemic targets in patients with type 2 diabetes mellitus treated with basal insulin in a real-world setting, and to determine physicians' beliefs and practices regarding these patients.

Methods: This study had two components; a retrospective analysis using a US claims database of patient and treatment data, and a survey of physicians' beliefs and practices.

Results: A total of 39,074 patients treated with basal insulin were included in this analysis.

Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes.

Objective: To determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes.

Research Design And Methods: A randomized, double-blind, placebo-controlled trial was performed in 15 adult patients with type 2 diabetes (HbA1c >7.5% [58 mmol/mol]) and hypertriglyceridemia (TG >200 and <500 mg/dL).

How well do glucose variability measures predict patient glycaemic outcomes during treatment intensification in type 2 diabetes?

Aim: Despite links to clinical outcomes in patients with type 2 diabetes mellitus (T2DM), the clinical utility of glycaemic variability (GV) measures is unknown. We evaluated the correlation between baseline GV, and glycated haemoglobin (HbA1c) attainment and hypoglycaemic events during treatment intensification in a large group of patients.

Methods: Patient-level data from six 24-week clinical trials of T2DM patients undergoing treatment intensification with basal insulin or comparators (N = 1699) were pooled.

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results.

Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.

FASTING VERSUS POSTPRANDIAL HYPERGLYCEMIA AS A TREATMENT TARGET TO LOWER ELEVATED HEMOGLOBIN A1C.

Objective: Postprandial hyperglycemia (PPHG) may need addressing when glycemic control cannot be maintained in patients with type 2 diabetes mellitus. We investigated whether glycated hemoglobin A1c (A1c) levels ≥7.0% can indicate postprandial defects warranting prandial therapy after optimized basal insulin therapy.

Sensitivity of Traditional and Risk-Based Glycemic Variability Measures to the Effect of Glucose-Lowering Treatment in Type 2 Diabetes Mellitus.

Background: Here we assess associations between glycemic variability (GV) measures and outcomes from glucose-lowering therapy in patients with type 2 diabetes (T2DM) to identify the metrics most sensitive to treatment response.

Methods: Data from 1699 patients in 6 previously reported studies in adults with T2DM treated with basal insulin and/or oral glucose-lowering drugs were included in a post hoc meta-analysis. Using 7-point blood glucose (BG) profiles we compared the GV metrics standard deviation (SD), mean amplitude of glycemic excursion (MAGE), mean absolute glucose (MAG), low and high BG risk indices (LBGI, HBGI), and average daily risk range (ADRR).

Type 2 diabetes mellitus treatment patterns in U.S. nursing home residents.

Background: The prevalence of type 2 diabetes mellitus (diabetes) in nursing home residents (NHRs) is increasing, concurrently with obesity and other comorbid conditions. NHR would benefit greatly from antidiabetic medications that would improve glycemic control and give a lower risk of hypoglycemia but that do not contribute to weight gain in obese individuals.

Objective: To examine the prescription patterns to NHRs with diabetes, including the use of newer injectable therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists.

How well do glucose variability measures predict patient glycaemic outcomes during treatment intensification in type 2 diabetes?

Aim: Despite links to clinical outcomes in patients with type 2 diabetes mellitus (T2DM), the clinical utility of glycaemic variability (GV) measures is unknown. We evaluated the correlation between baseline GV, and glycated haemoglobin (HbA1c) attainment and hypoglycaemic events during treatment intensification in a large group of patients.

Methods: Patient-level data from six 24-week clinical trials of T2DM patients undergoing treatment intensification with basal insulin or comparators (N=1699) were pooled.

Prandial insulin versus glucagon-like peptide-1 added to basal insulin: comparative effectiveness in the community practice setting.

Background: Real-world data on emerging combination approaches for type 2 diabetes mellitus (T2DM) management are limited. The objective of the current study was to document the characteristics and clinical outcomes of patients with T2DM initiating prandial insulin or a glucagon-like peptide-1 (GLP-1) receptor agonist while on basal insulin.

Methods: This was a retrospective analysis of an electronic medical records database of patients with T2DM managed in a community practice setting in the United States.

Patterns of postprandial hyperglycemia after basal insulin therapy: individual and regional differences.

Background: Treatment of postprandial hyperglycemia could be needed when basal insulin added to oral therapy does not maintain glycated haemoglobin (HbA1C ) targets in type 2 diabetes mellitus. Knowing individual and regional patterns of postprandial hyperglycemia in this setting might improve therapeutic decisions.

Methods: Patient-level self-monitored blood glucose data were pooled from six studies of insulin glargine for patients with HbA1C  ≥ 7.

Adding Rapid-Acting Insulin or GLP-1 Receptor Agonist to Basal Insulin: Outcomes in a Community Setting.

Objective: To evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.

Methods: Data were extracted retrospectively from a U. S.

Contributions of basal and prandial hyperglycemia to total hyperglycemia in older and younger adults with type 2 diabetes mellitus.

Objectives: To evaluate the relative contributions of basal and prandial components to total hyperglycemia in older and younger adults with type 2 diabetes mellitus.

Design: Participant-level data were pooled from six randomized studies of 24 weeks or longer treatment with insulin glargine or an active comparator.

Setting: Prospective, randomized Phase 3 or 4 controlled trials.

Efficacy and safety of insulin glargine compared to other interventions in younger and older adults: a pooled analysis of nine open-label, randomized controlled trials in patients with type 2 diabetes.

Objective: Elderly patients with type 2 diabetes mellitus (T2DM) present therapeutic challenges related to co-morbidities, treatment adherence, and safety. This study examines the efficacy and safety of insulin glargine compared to other glucose-lowering interventions in younger and older adults.

Methods: In this pooled analysis of 24-week data from nine prospective open-label, multicenter, phase 3/4, two-arm, parallel-group, randomized controlled trials, patients with T2DM aged 18-80 years received insulin glargine (used as a basal insulin regimen) or comparators (including rosiglitazone, pioglitazone, insulin lispro, insulin lispro 75/25, NPH insulin, NPH insulin 30/70, and lifestyle/dietary measures).

Comparing the effects of insulin glargine and thiazolidinediones on plasma lipids in type 2 diabetes: a patient-level pooled analysis.

Background: The prevalence of dyslipidaemia and the risk of cardiovascular disease are elevated in patients with type 2 diabetes. This analysis compared the effects of insulin glargine versus thiazolidinediones (TZDs) on lipid profiles.

Methods: Patient-level data were pooled from two randomized clinical studies.

Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes.

Objective: To determine the relative contributions of basal hyperglycemia (BHG) versus postprandial hyperglycemia (PPHG) before and after treatment intensification in patients with glycated hemoglobin A(1c) (A1C) >7.0% while on prior oral therapy.

Research Design And Methods: Self-measured, plasma-referenced glucose profiles and A1C values were evaluated from participants in six studies comparing systematically titrated insulin glargine with an alternative regimen (adding basal, premixed, or prandial insulin, or increasing oral agents).

Comparison of methods for delivering a lifestyle modification program for obese patients: a randomized trial.

Background: Physicians frequently prescribe medications for weight loss but offer minimal lifestyle counseling despite the additional benefits of combining both interventions.

Objective: To compare 5 methods of delivering a lifestyle modification program to obese patients receiving sibutramine.

Design: Randomized, 6-month, open-label study.

Effects of cholesteryl ester transfer protein inhibition on apolipoprotein A-II-containing HDL subspecies and apolipoprotein A-II metabolism.

This study was designed to establish the mechanism responsible for the increased apolipoprotein (apo) A-II levels caused by the cholesteryl ester transfer protein inhibitor torcetrapib. Nineteen subjects with low HDL cholesterol (<40 mg/dl), nine of whom were also treated with 20 mg of atorvastatin daily, received placebo for 4 weeks, followed by 120 mg of torcetrapib daily for the next 4 weeks. Six subjects in the nonatorvastatin cohort participated in a third phase, in which they received 120 mg of torcetrapib twice daily for 4 weeks.