Influence of obesity on plasma lipoproteins, glycaemia and insulinaemia in patients with familial combined hyperlipidaemia

Abstract

The in¯uence of obesity on blood pressure and plasma lipoproteins, glucose and insulin levels was investigated in patients with familial combined hyperlipidaemia (FCH). Sixty seven FCH patients mean age 49.0 AE 8.9 y (45 male, 22 female) de®ned as obese (BMI ! 27 kg/m 2 , n 39) or non-obese (BMI`27 kg/m 2 , n 28) were compared with control subjects matched for age, gender and body weight. Blood pressure, plasma lipoproteins, glucose and insulin were measured at baseline and following standard oral glucose load. The analysis indicate that FCH subjects with BMI ! 27 kg/m 2 had signi®cantly higher systolic and diastolic blood pressure, blood glucose and insulin levels following oral glucose tolerance test than those with BMI`27 kg/m 2 . Fasting plasma insulin values were also signi®cantly higher in the BMI ! 27 kg/m 2 subjects (138.5 AE 66.6 vs 111.0 AE 29.9 pmol/l, respectively, P`0.05). Quanti®cation of the area under the curve of the insulin secretion showed hyperinsulinaemia in 64.1% of patients with BMI ! 27 kg/m 2 compared to 28.5% in the group with BMI`27 kg/m 2 (P`0.01). Plasma insulin values were positively related to triglyceridaemia. There were no differences in the plasma lipid values between the two FCH groups. We conclude that fasting and post-glucose stimulated plasma insulin levels are frequent ®ndings in patients with FCH when compared with control subjects of similar age, gender and BMI. Moreover, obesity (BMI ! 27 kg/m 2 ) exacerbates the hyperglycaemia, hyperinsulinaemia and blood pressure values in these FCH subjects. These factors, together with lipid abnormalities, can predispose to the elevated risk of cardiovascular disease observed in FCH subjects.

Subclasses of Low-Density Lipoprotein and Very Low-Density Lipoprotein in Familial Combined Hyperlipidemia: Relationship to Multiple Lipoprotein Phenotype

“…Subjects with FCHL present with a complex phenotype whose expression is influenced by genetic, metabolic, and environmental factors. [3][4][5][6] Affected FCHL relatives are viscerally obese, 2,4,7 hyperinsulinemic, 3 insulin-resistant, 5,7 and can show a number of abnormalities in lipid metabolism: hypercholesterolemia and/or hypertriglyceridemia, elevated apolipoprotein B (apoB) levels, small dense low-density lipoprotein (sd LDL), and decreased plasma high-density lipoprotein (HDL) cholesterol concentrations.…”

Impaired Free Fatty Acid Suppression During Hyperinsulinemia Is a Characteristic Finding in Familial Combined Hyperlipidemia, but Insulin Resistance Is Observed Only in Hypertriglyceridemic Patients

“…[11][12][13] This observation indicates that overweight is only a modifying factor for insulin sensitivity in FCHL. 14 A defect in insulin action in adipose tissue is likely to play a significant role in FCHL because insulin's suppressive effect on free fatty acid (FFA) levels is impaired in FCHL patients. 10,12,15 High FFA levels may in turn lead to both a decrease in insulin-stimulated glucose uptake in adipose tissue and skeletal muscle, according to the scheme proposed by Randle et al, 16 and to an increase in the synthesis of lipoproteins in the liver.…”

A Major Gene Effect on Fasting Insulin and Insulin Sensitivity in Familial Combined Hyperlipidemia

“…Because patients with FCHL have several components of the metabolic syndrome, e.g., hypertriglyceridemia (2,3), postprandial lipemia (33), high prevalence of small, dense LDL particles (14,34,35), low HDL cholesterol levels (36,37), and central obesity (38), it is not surprising that these patients also have hyperinsulinemia (33,37) as a result of insulin resistance (4 -6). Our earlier studies suggested that insulin resistance also is present in young relatives of FCHL patients who are at risk to develop FCHL.…”