Tu T. Nguyen

Hyperlipidemia and Diabetes Mellitus

The increased risk of coronary artery disease in subjects with diabetes mellitus can be partially explained by the lipoprotein abnormalities associated with diabetes mellitus. Hypertriglyceridemia and low levels of high-density lipoprotein are the most common lipid abnormalities. In type 1 diabetes mellitus, these abnormalities can usually be reversed with glycemic control. In contrast, in type 2 diabetes mellitus, although lipid values improve, abnormalities commonly persist even after optimal glycemic control has been achieved. Screening for dyslipidemia is recommended in subjects with diabetes mellitus. A goal of low-density lipoprotein cholesterol of less than 130 mg/dL and triglycerides lower than 200 mg/dL should be sought. Several secondary prevention trials, which included subjects with diabetes, have demonstrated the effectiveness of lowering low-density lipoprotein cholesterol in preventing death from coronary artery disease. The benefit of lowering triglycerides is less clear. Initial approaches to lowering the levels of lipids in subjects with diabetes mellitus should include glycemic control, diet, weight loss, and exercise. When goals are not met, the most common drugs used are hydroxymethylglutaryl coenzyme A reductase inhibitors or fibrates.

Cholesterol-Lowering Effect of Stanol Ester in a US Population of Mildly Hypercholesterolemic Men and Women: A Randomized Controlled Trial

OBJECTIVE To determine the efficacy of stanol esters in lowering cholesterol in a US population. SUBJECTS AND METHODS After a run-in phase, 318 subjects were randomized to receive one of the following margarine-like spreads containing stanol ester or placebo for 8 weeks: EU 3 G: 1 g of stanol (ester form) per 8-g serving of a European formula 3 times a day; US 3 G: 1 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; US 2 G: 0.67 g of stanol (ester form) per 8-g serving of a US reformulation 3 times a day; or placebo spread. RESULTS Mean +/- SD baseline total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 233+/-20 and 153+21 mg+/-dL, respectively. In the US 3 G group, 3 g daily of stanol esters lowered TC and LDL-C levels by 6.4% and 10.1%, respectively. There was a dose-dependent response compared with 2 g daily (US 2 G). Triglyceride and high-density lipoprotein cholesterol levels were unchanged. The incidence of adverse effects was not different from placebo. Serum vitamin A and 25-hydroxyvitamin D levels were not affected. CONCLUSIONS Stanol esters lowered TC and LDL-C levels in a mildly hypercholesterolemic US population without evidence of adverse effects. It may be a useful dietary adjunct to lower cholesterol.

The effect of the treatment of hypothyroidism and hyperthyroidism on plasma lipids and apolipoproteins AI, AII and E

OBJECTIVE Although lipid abnormalities are well described in hypothyroidism, effects on apolipoproteins are less well understood. The aim of this study was to examine the effects of thyroid dysfunction on plasma lipids and apolipoproteins.

Lipids and Lipoproteins in Women

Coronary artery disease (CAD) is the most common cause of death in women in the United States. Dyslipidemia is a risk factor for CAD in both men and women. Low levels of high-density lipoprotein (HDL) cholesterol and hypertriglyceridemia, especially in association with a dense low-density lipoprotein (LDL) phenotype, may be of greater importance in women than in men. The relationship between CAD and dyslipidemia and the therapeutic approach to disorders of lipid metabolism in women have unique features because of the effects of exogenous and endogenous hormones on lipid pathways. Estrogen decreases LDL cholesterol and Lp(a) lipoprotein and increases triglyceride and HDL cholesterol levels. Progestogens decrease triglycerides, HDL cholesterol, and Lp(a), and they increase LDL cholesterol. Thus, oral contraceptives increase plasma triglycerides, whereas the effect of these agents on LDL cholesterol and HDL cholesterol levels is related to the androgenicity and dose of progestogen. Postmenopausal hormone replacement therapy increases triglycerides and decreases LDL cholesterol. The effect of hormone replacement therapy on HDL cholesterol is influenced by the addition of progestogen. Although no primary prevention studies have analyzed lipid lowering and CAD in women, secondary prevention studies have suggested that the response to drug treatment and the benefit of lipid lowering are similar in women and in men. Hormone replacement therapy should be considered in the treatment of hypercholesterolemia in postmenopausal women; however, individualization of treatment is important to avoid adverse effects.

Effect of Thyroid Hormone Replacement on Lipoprotein(a), Lipids, and Apolipoproteins in Subjects With Hypothyroidism

OBJECTIVE To study the effect of thyroid hormone replacement on total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I and B-100, and lipoprotein(a) [Lp(a)] in subjects with hypothyroidism. MATERIAL AND METHODS In 17 patients with clinical primary hypothyroidism, studies were done before and after thyroid hormone replacement therapy. Free thyroxine and thyrotropin were determined by chemiluminescent assay. Total cholesterol and triglycerides were measured by enzymatic methods, and HDL-C was measured after dextran sulfate-MgCl2 precipitation. Apolipoprotein A-I and B-100 were assayed by immunonephelometry. For measurement of Lp(a), we used a sequential sandwich enzyme-linked immunosorbent assay. RESULTS After levothyroxine treatment, the mean concentration of thyrotropin decreased from 91.4 to 3.7 microIU/mL, and free thyroxine increased from 0.5 to 1.2 ng/ dL. Total cholesterol, triglycerides, HDL-C, low-density lipoprotein cholesterol, and apolipoprotein A-I and B-100 decreased after thyroid hormone replacement therapy. Lp(a) levels also decreased significantly (P<0.05) after treatment, from a mean of 33.4 to 25.6 mg/dL. CONCLUSION Hypothyroidism is associated with an increase in total cholesterol, triglycerides, HDL-C, apolipoprotein A-I and B-100, and Lp(a). A reduction in lipid and lipoprotein levels after thyroid hormone replacement in our study cohort resulted in a less atherogenic profile.

Predictors of Macrovascular Disease in Patients With Type 2 Diabetes Mellitus

OBJECTIVE To assess the importance of classic and nonclassic risk factors in the development of coronary artery disease (CAD) or cerebrovascular disease (CVD) in patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS In this community-based, prospective cohort study, quantitative measurements for cholesterol, triglycerides (TGs), glucose, and lipoprotein(a) detected as a sinking pre-beta-lipoprotein band on electrophoresis were obtained from 1968 through 1982 from 449 patients who were free of CAD and CVD but had type 2 DM. Demographic data and covariables obtained were age, body mass index, duration of diabetes, sex, smoking, and hypertension. The relationship of individual continuous factors to the development of CAD and CVD as well as multivariate models were evaluated with use of the Cox proportional hazards model. The primary outcome was to determine which risk factors are associated with development of CAD or CVD in patients with type 2 DM. RESULTS After a mean follow-up of 13 years, 216 CAD and 115 CVD events had developed. The hazard ratio estimates with 95% confidence intervals (CIs) for CAD after multivariate analysis were significant for age, 1.45 (95% CI, 1.27-1.67); fasting glucose levels at enrollment, 1.63 (95% CI, 1.17-2.25); smoking, 1.45 (95% CI, 1.10-1.91); and TGs, 1.49 (95% CI, 1.15-1.92). The hazard ratio estimates for CVD were significant for age, 1.95 (95% CI, 1.59-2.38); hypertension, 1.89 (95% CI, 1.30-2.74); fasting glucose levels at enrollment, 1.69 (95% CI, 1.06-2.70); and smoking, 1.57 (95% CI, 1.07-2.30). CONCLUSION In diabetic patients, age, fasting glucose levels, smoking, and TG levels are independent risk factors for development of CAD events. Age, hypertension, glucose, and smoking predicted development of CVD events.

Lipids and Lp(a) Lipoprotein Levels and Coronary Artery Disease in Subjects With Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE To determine whether increased Lp(a) lipoprotein levels are associated with either non-insulin-dependent diabetes mellitus (NIDDM) or coronary artery disease (CAD) in patients with NIDDM and to examine the relationship between Lp(a) levels and glycemic control. DESIGN We conducted a cross-sectional study of subjects with NIDDM who were participants in the Rochester Diabetic Neuropathy Study and healthy control subjects from the population of Rochester, Minnesota. MATERIAL AND METHODS Lipids and Lp(a) lipoprotein levels were compared in 227 subjects with NIDDM and 163 control subjects and, among the subjects with NIDDM, in those with (N = 96) and without (N = 131) CAD. The correlation between Lp(a) levels and glycosylated hemoglobin was investigated. RESULTS Subjects with NIDDM had higher triglyceride and lower high-density lipoprotein cholesterol levels than did control subjects. Subjects with NIDDM and CAD had higher total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and lower high-density lipoprotein cholesterol levels than did subjects with NIDDM without CAD. Subjects with NIDDM had significantly higher Lp(a) levels than did control subjects, but subjects with NIDDM and CAD did not have significantly higher Lp(a) levels than did those without CAD. Among subjects with NIDDM, the level of Lp(a) was not significantly correlated with glycosylated hemoglobin. CONCLUSION Although subjects with NIDDM have higher Lp(a) levels than do control subjects, Lp(a) does not seem to be associated with CAD in subjects with NIDDM. In this study, no association was found between Lp(a) level and glycemic control.

Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E-rich very low density lipoprotein fraction

To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.

Clomiphene-induced severe hypertriglyceridemia and pancreatitis

Clomiphene has been available for clinical use since 1960 and has been successfully used to aid fertility in women with certain anovulatory disorders. It is a synthetic estrogen analog, of the triphenylethylene derivative group, and its biochemical structure is similar to that of tamoxifen. Estrogen and tamoxifen lower total and low-density lipoprotein cholesterol and increase triglyceride and high-density lipoprotein cholesterol levels. In patients with baseline hypertriglyceridemia, these agents can induce severe hypertriglyceridemia and pancreatitis. The actions of clomiphene on lipid metabolism have not been studied, and to our knowledge, no cases of severe hypertriglyceridemia related to the use of clomiphene have been described. We report the case of a woman who developed 2 episodes of clomiphene-induced hypertriglyceridemia and pancreatitis while receiving this drug for treatment of infertility. Given the striking structural similarity between clomiphene and tamoxifen, it is likely that clomiphene is capable of inducing severe hypertriglyceridemia in patients with certain underlying lipid disorders by a mechanism similar to that of tamoxifen.

Nicotinic Acid-Induced Toxicity Associated With Cytopenia and Decreased Levels of Thyroxine-Binding Globulin

We report the occurrence of cytopenia and hypothyroxinemia attributed to decreased levels of thyroxine-binding globulin in patients receiving nicotinic acid. We describe two patients in whom hypothyroxinemia developed while they were taking nicotinic acid; these patients also had decreased levels of thyroxine-binding globulin. Results of all thyroid function tests returned to normal when use of the nicotinic acid was discontinued. In one patient, leukopenia and thrombocytopenia developed during nicotinic acid therapy alone. These conditions were reversed after the drug regimen was discontinued. In another patient, leukopenia and thrombocytopenia developed during combination nicotinic acid and lovastatin therapy. When administration of both drugs was discontinued, the hematologic abnormalities, which could have been due to either nicotinic acid or lovastatin, diminished. We suggest that cytopenia may develop in patients receiving nicotinic acid; thus, thyroid function tests should be interpreted in light of a possible decreased level of thyroxine-binding globulin.