LDLR promoter variant and exon 14 mutation on the same chromosome are associated with an unusually severe FH phenotype and treatment resistance.

Familial hypercholesterolemia (FH) is the most common form of autosomal-dominant hypercholesterolemia, and is caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Heterozygous FH is characterized by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular disease, whereas homozygous FH results in more severe LDL cholesterol elevation with death by 20 years of age. We present here the case of an African-American female FH patient presenting with a myocardial infarction at the age of 48, recurrent angina pectoris and numerous coronary artery stents.

Patient-important outcomes in registered diabetes trials.

Context: Concerns about the safety and efficacy of diabetes interventions persist, in part because randomized clinical trials (RCTs) have not measured their effect on patient-important outcomes, ie, death and quality of life (morbidity, pain, function).

Objective: To systematically determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes.

Data Sources: On November 10, 2007, we searched primary RCT registries ClinicalTrials.

Pilot study of combined therapy with ω-3 fatty acids and niacin in atherogenic dyslipidemia.

Background: Niacin and ω-3 fatty acids (ω-3 FA) are both nutrients that reduce serum triglyceride and raise high-density lipoprotein cholesterol (HDL-C) levels when used at pharmacological doses. The possibility that these two agents, given in combination, might have additive effects on these lipid parameters has not been examined previously. In addition, the combination might prevent the rise in low-density lipoprotein (LDL)-C levels frequently seen with ω-3 FA treatment.

Glycemic variation and hypoglycemia in patients with well-controlled type 1 diabetes on a multiple daily insulin injection program with use of glargine and ultralente as basal insulin.

Objective: To evaluate glycemic variation and hypoglycemia in patients with well-controlled type 1 diabetes receiving multiple daily insulin injections during glargine and Ultralente use as basal insulin in a clinical trial.

Methods: Twenty-two patients (12 men and 10 women; median age, 43 years), with a hemoglobin A1c level <7.8%, were randomized in a crossover design to receive either insulin glargine or Ultralente insulin as basal insulin for 4 months each, with insulin aspart as prandial insulin.

Waking up from the DREAM of preventing diabetes with drugs.

The current epidemic of diabetes makes a drug to prevent it attractive. But despite promotion of recent research evidence, , , and argue that we are not there yet

Comparison of apolipoprotein-B/apolipoprotein-AI in subjects with versus without the metabolic syndrome.

Recent studies have suggested that the apolipoprotein-B (apo-B)/apolipoprotein-AI (apo-AI) ratio predicts cardiovascular risk better than any of the cholesterol indexes. The aim of the present study was to assess if the apo-B/apo-AI ratio is related to the metabolic syndrome and its components. Data were analyzed from 2,964 subjects (mean age 48 years; 1,516 men, 1,448 women) from the National Health and Nutrition Examination Survey III with apolipoprotein data who were evaluated for the metabolic syndrome and its components.

Low-density lipoprotein cholesterol lowering in the prevention of CHD: how low should we go?

The past 12 years have seen the publication of numerous randomized placebo-controlled studies using statins to lower low-density lipoprotein cholesterol (LDLC) to assess the efficacy of cholesterol lowering on cardiovascular events. Initial studies predominantly evaluated mortality or nonfatal myocardial infarctions and coronary heart disease (CHD) death in patients with known or presumed established coronary disease and moderately elevated to very elevated serum cholesterol concentrations. Subsequent investigations studied a broader spectrum of cardiovascular events as a composite primary end point in both primary and secondary prevention strategies in subjects with lower mean entry serum LDLC concentrations.

The effect of high dose simvastatin on, platelet size in patients with, type 2 diabetes mellitus.

Statins reduce coronary heart disease risk by altering blood lipids and other mechanisms. One of the possible other mechanisms is through an effect on thrombosis. We assessed the effect of simvastatin 80 mg daily versus placebo given in a single blind crossover fashion on platelet size in response to standard ex vivo stimuli, a surrogate for platelet activation, in 12 subjects with type 2 diabetes and mixed dyslipidemia.

Rationale, design, and methods for glycemic control in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial.

A major therapeutic question in considering accelerated atherogenesis in patients with type 2 diabetes mellitus is whether reducing insulin resistance, as a proximal defect of a host of proatherogenic abnormalities including hyperglycemia, will be superior for decreasing mortality and coronary artery disease (CAD) risk compared with treating hyperglycemia to overcome insulin resistance with insulin-providing agents. This question is highly relevant, since earlier targeted glycemic control trials utilizing conventional glucose-lowering strategies that increase insulin levels have generally failed to reduce CAD risk despite markedly reducing microvascular risk. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial seeks to determine whether primarily using an insulin-sensitizing strategy for treatment of type 2 diabetes is superior when compared with primarily using an insulin-providing strategy with regard to cardiovascular outcomes.

The effect of high-dose simvastatin on free fatty acid metabolism in patients with type 2 diabetes mellitus.

Statins improve all major lipid fractions, reduce coronary heart disease risk, and may have a minor effect on glucose tolerance. A reduction in free fatty acid flux and concentrations could be partly responsible for these effects. We measured nocturnal and postprandial plasma palmitate concentrations and rate of appearance (R(a)) on 2 occasions in 12 obese dyslipidemic subjects with type 2 diabetes mellitus, using a single-blind, crossover format (placebo followed by simvastatin, 80 mg/d), and also on 1 occasion in 6 untreated control subjects.

The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus.

Statins decrease triglycerides (TGs) in addition to decreasing low density lipoprotein-cholesterol. Although the mechanism for the latter effect is well understood, it is still unclear how TG decrease is achieved with statin therapy. Because hypertriglyceridemia is common in obese patients with type 2 diabetes mellitus, we studied triglyceride-rich lipoprotein triglyceride (TRL-TG) turnover in 12 such subjects using stable isotopically labeled glycerol.

Randomized controlled clinical trial of glargine versus ultralente insulin in the treatment of type 1 diabetes.

Objective: Multiple daily insulin injection programs are commonly accompanied by considerable glycemic variation and hypoglycemia. We conducted a randomized crossover design clinical trial to compare glargine with ultralente insulin as a basal insulin in type 1 diabetes.

Research Design And Methods: To determine whether the use of glargine insulin as a basal insulin would result in a comparable HbA1c and less glycemic variation and hypoglycemia than ultralente insulin, 22 individuals (aged 44 +/- 14 years [+/-SD], 55% men) with type 1 diabetes who were experienced with multiple daily insulin injections and had an HbA1c of <7.

Systemic and forearm triglyceride metabolism: fate of lipoprotein lipase-generated glycerol and free fatty acids.

Little is known about the fate of the lipolytic products produced by the action of lipoprotein lipase (LPL) on circulating triglyceride-rich lipoproteins in humans. We studied eight lean, healthy male subjects after an overnight fast. Subjects received infusions of lipid emulsions containing triolein labeled with (3)H on both the glycerol backbone and the fatty acid portion of the molecule; (14)C glycerol and (14)C oleate were coinfused to quantify the systemic and forearm release of (3)H glycerol and (3)H oleate resulting from LPL action.