Insulin Resistance, Metabolic Syndrome X
Conditions
Keywords
fenofibrate, niacin, rosiglitazone, LDL phenotype pattern B, small, dense LDL, insulin resistance, Metabolic Syndrome
Brief summary
Lipid abnormalities in people with the Metabolic Syndrome (the Insulin Resistance Syndrome) are characterized by elevations in triglycerides and LDL cholesterol; low levels of HDL cholesterol; and small, dense LDL particles. Statins generally do not change LDL particle size, so often fenofibrate is added. This combination may still not be sufficient. Niacin is a common third drug added to the treatment regimen, but niacin can increase insulin resistance. This study compares niacin as a third drug to rosiglitazone, an insulin sensitizer.
Detailed description
The Metabolic Syndrome is characterized by an atherogenic dyslipidemia consisting of hypertriglyceridemia, modest elevations of LDL cholesterol, low levels of HDL cholesterol, and LDL phenotype pattern B (small, dense LDL particles). Statins are first line therapy, and reduce LDL cholesterol levels without affecting LDL particle size. Fenofibrate addresses the triglycerides, HDL cholesterol levels, and LDL phenotype, so is recommended as second level therapy. The third element is niacin, but for insulin resistant patients, a question has been whether niacin might be exacerbating the underlying pathophysiology of Metabolic Syndrome patients. In SNARED, niacin was compared to the insulin sensitizer rosiglitazone in study subjects already on statin and fenofibrate. All volunteers participating in SNARED exhibit LDL phenotype pattern B despite statin therapy at the time of recruitment. Comparisons of LDL phenotype at baseline are to be compared to measurements made after 4 months of statin + fenofibrate. If the LDL phenotype converts to pattern A (large LDL particles), this is a study endpoint. Otherwise, study subjcts are randomized to receive statin+fenofibrate+niacin, or statin+fenofibrate+rosiglitazone for six months, at which time lipid phenotype will again be determined..
Interventions
DRUGfenofibrate
DRUGniacin
DRUGrosiglitazone
Sponsors
GlaxoSmithKline
Kos Pharmaceuticals
Abbott
Foundation Research, Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age \>= 18 years Fasting triglycerides \> 100 mg/dL Fasting plasma glucose 110-128 mg/dL Non-pattern A LDL phenotype
Exclusion criteria
* Overt diabetes mellitus Current therapy with hypoglycemic agents Secondary causes of dyslipidemia (e.g. HRT, thyroid disease) Serum creatinine \> 2.5 mg/dL or nephrotic syndrome AST/ALT \> 3X upper limits of normal Known gallbladder disease History of gout or hyperuricemia History of peptic ulcer disease Hypersensitivity or intolerance to any of the study drugs Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The effect of treatment on Peak LDL particle size | — |
Secondary
| Measure | Time frame |
|---|---|
| traditional lipid parameters (LDL-C, HDL-C, triglycerides) | — |
| % of lipids in regions IIIa+IIIb of a gradient gel electrophoresis | — |
| The effect of treatment on: | — |
| fasting glucose | — |
| Hemoglobin A1c | — |
| LDL phenotype | — |
Countries
United States
Outcome results
None listed