Hyperlipidemias: Fonseca VA

Goldfine AB, Fonseca VA. · Joslin Diabetes Center, Boston, MA 02115, USA. · Postgrad Med. · Pubmed #19494473 No free full text.

Abstract: Therapy is often required to manage the hyperglycemia, hypertension, and dyslipidemia that occur in patients with type 2 diabetes mellitus (T2DM) in order to control the risk of cardiovascular (CV) events. The importance of managing these risk factors is underscored by the recommendation from the American Diabetes Association and the American Association of Clinical Endocrinologists for treatment of these CV risk factors to target levels. However, relatively few patients achieve simultaneous control of these risk factors. As such, therapy that has positive effects on more than 1 risk factor is of potential benefit. Initially approved as a lipid-lowering agent, the bile acid sequestrant colesevelam hydrochloride (HCl) is now also approved as an adjunct therapy to improve glycemic control in patients with T2DM. This review summarizes the major findings of clinical studies that investigated the glucose-and lipid-lowering effects of colesevelam HCl when added to stable metformin-, sulfonylurea-, or insulin-based antidiabetes therapies in patients with T2DM.

Fonseca VA. · Department of Medicine, Section of Endocrinology, Tulane University School of Medicine, New Orleans, Louisiana 70112-2699, USA. · Clin Cornerstone. · Pubmed #16473262 No free full text.

Abstract: The metabolic syndrome is a cluster of cardiovascular risk factors associated with obesity. The defining components of the metabolic syndrome, according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), are elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose. The pathophysiologic basis of metabolic syndrome is complex and reflects several interrelated disturbances of glucose and lipid homeostasis. Metabolic syndrome is prevalent in the United States and developed nations, and patients with this disorder are at risk for type 2 diabetes mellitus and cardiovascular disease, underscoring the need for prompt patient identification and management. The first-line approach to control of metabolic syndrome is weight control and exercise. A wide range of pharmacologic interventions (eg, statins, antihypertensive drugs, insulin sensitizers, and thiazolidinediones) have been shown to be effective in controlling the individual components of metabolic syndrome. Obesity, which is a necessary component of metabolic syndrome, has reached epidemic proportions in the United States. Although lifestyle management or medications can control the underlying risk factors and most of the components of metabolic syndrome, long-term weight loss is difficult to achieve. Several promising pharmacologic interventions that may have an important role in the management of metabolic syndrome by treating adipose tissue-mediated metabolic disturbances are in the early stages of development.

Kunhiraman BP, Jawa A, Fonseca VA. · Section of Endocrinology, Diabetes, and Metabolism, Tulane University and Hospital, 1430 Tulane Avenue, New Orleans, LA 70112, USA. · Endocrinol Metab Clin North Am. · Pubmed #15752925 No free full text.

Abstract: A multiple risk factor approach is needed in patients who have type 2 diabetes. Because many risk factors are linked with IR, treatment with insulin sensitizers has the potential to modulate these risk factors favorably. TZDs 'have many important effects beyond lowering blood glucose. By targeting IR, they improve many cardiovascular risk factors that are associated with the IR syndrome. In particular, they increase HDL-C, have anti-inflammatory effects, improve endothelial function and fibrinolysis, and decrease carotid intimal thickness; however, no evidence-based studies on cardiovascular outcomes are available to substantiate the potential cardioprotective effects of TZDs. Several clinical trials that were designed to investigate the effect that these agents have on reducing cardiovascular events are well under way.

Fonseca VA. · Department of Medicine, and Pharmacology, Tulane University Health Sciences Center, New Orleans, Lousiana 70112, USA. · Am J Cardiol. · Pubmed #12957327 No free full text.

Abstract: Patients with diabetes have a greatly increased relative risk of developing cardiovascular disease when compared with patients without diabetes. Much of this risk is related to insulin resistance and is associated with both traditional and nontraditional cardiovascular risk factors. Therapy for diabetes must address these risk factors in an attempt to prevent and adequately treat cardiovascular disease. Pharmacologic therapy directed toward dyslipidemia and hypertension has a beneficial effect on risk factors and has been shown to decrease cardiovascular events. The effects of insulin and oral hypoglycemic agents on insulin resistance are variable, and their direct effect on cardiovascular disease is less clear. Metformin is the only oral hypoglycemic agent shown to decrease cardiovascular events independent of glycemia. The thiazolidinediones directly improve insulin resistance, decrease plasma insulin concentration, and have the potential to decrease the risk of cardiovascular disease in patients with diabetes. A number of studies have demonstrated that the thiazolidinediones produce changes in several cardiovascular risk factors associated with the insulin resistance syndrome, including lowering blood pressure, correcting diabetic dyslipidemia, improving fibrinolysis, and decreasing carotid artery intima-medial thickness. These agents bind a newly described class of receptors, peroxisome proliferator-activated receptors, which may have implications for atherosclerosis. Although these drugs increase low-density lipoprotein (LDL) cholesterol, they induce a favorable change in the LDL particle size and susceptibility to oxidation. Long-term clinical trials are being conducted to determine the effect that thiazolidinediones have on cardiovascular events in individuals with type 2 diabetes.

Gouda BP, Asnani S, Fonseca VA. · Department of Medicine, Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, LA, USA. · Compr Ther. · Pubmed #12506489 No free full text.

Abstract: The thiazolidinediones are the insulin sensitizers used in the management of Type 2 diabetes mellitus. These drugs can potentially decrease the risk of cardiovascular disease by correcting the different components of the insulin resistance syndrome.

Granberry MC, Fonseca VA. · Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, John L. McClellan Memorial Medical Center, Little Rock, USA. · South Med J. · Pubmed #9932820 No free full text.

Abstract: BACKGROUND: Insulin resistance is characterized by impaired responsiveness to endogenous or exogenous insulin. Loss of responsiveness is associated with a "clustering" of cardiovascular risk factors that includes abdominal obesity, hypertension, dyslipidemia, glucose intolerance, and hyperinsulinemia; this association is referred to as the insulin resistance syndrome (IRS). METHODS: We searched MEDLINE, using the term insulin resistance, and reviewed relevant publications. RESULTS: We review the mechanisms and clinical consequences attributed to IRS, along with patient assessment and treatment options. CONCLUSIONS: It is possible to improve insulin sensitivity by caloric restriction, weight loss, exercise, and drug therapy. Metformin and troglitazone, approved for use in the treatment of type 2 diabetes mellitus (DM), improve insulin sensitivity and lower plasma glucose concentrations. Several other medications that may improve insulin sensitivity are currently under clinical investigation. Studies are needed to determine the effect of these medications on morbidity and mortality of patients with insulin resistance and type 2 DM.

Goldberg RB, Fonseca VA, Truitt KE, Jones MR. · Lipid Disorders Clinic, Division of Endocrinology Diabetes and Metabolism, and Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Arch Intern Med. · Pubmed #18663165 links to  free full text

Abstract: BACKGROUND: Poor glycemic control is a risk factor for microvascular complications in patients with type 2 diabetes mellitus. Achieving glycemic control safely with insulin therapy can be challenging. METHODS: A prospective, 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study conducted at 50 sites in the United States and 1 site in Mexico between August 12, 2004, and December 28, 2005. Subjects had type 2 diabetes mellitus that was not adequately controlled (glycated hemoglobin level, 7.5%-9.5%, inclusive) receiving insulin therapy alone or in combination with oral antidiabetes agents. In total 287 subjects (52% men; mean age, 57 years; with a mean baseline glycated hemoglobin level of 8.3%) were randomized: 147 to receive colesevelam hydrochloride, 3.75 g/d, and 140 to receive placebo. RESULTS: Using the least squares method, the mean (SE) change in glycated hemoglobin level from baseline to week 16 was -0.41% (0.07%) for the colesevelam-treated group and 0.09% (0.07%) for the placebo group (treatment difference, -0.50% [0.09%]; 95% confidence interval, -0.68% to -0.32%; P < .001). Consistent reductions in fasting plasma glucose and fructosamine levels, glycemic-control response rate, and lipid control measures were observed with colesevelam. As expected, the colesevelam-treated group had a 12.8% reduction in low-density lipoprotein cholesterol concentration relative to placebo (P < .001). Of recipients of colesevelam and placebo, respectively, 30 and 26 discontinued the study prematurely; 7 and 9 withdrew because of protocol-specified hyperglycemia, and 10 and 4 withdrew because of adverse events. Both treatments were generally well tolerated. CONCLUSIONS: Colesevelam treatment seems to be safe and effective for improving glycemic control and lipid management in patients with type 2 diabetes mellitus receiving insulin-based therapy, and it may provide a novel treatment for improving dual cardiovascular risk factors.