Insulin resistance in patients with familial combined hyperlipidemia and coronary artery disease.

The minimum model modified by the administration of insulin provides an objective and relatively easily measured index of peripheral sensitivity to insulin which was significantly lower (p <0.02) in familial combined hyperlipidemia (FCH) with ischemic heart disease (IHD) than in FCH without IHD and in control subjects (1.2 +/- 0.6, 1.9 +/- 1.0, 2.9 +/- 1.2 x 10(-4) mU/L/ min, respectively). In patients with FCH, insulin resistance explains, at least in part, their metabolic alterations (hypertension, abnormal glucose tolerance, hyperinsulinemia) and elevated IHD.

Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia.

The study objective was to investigate the relationship of insulin resistance (IR) with the lipoprotein phenotype in familial combined hyperlipidemia (FCH). Thirty-seven FCH men diagnosed by clinical and biochemical criteria and classified as lipoprotein phenotype IIa (n = 9), IIb (n = 17), or IV (n = 11) were compared with a healthy control group of 30 men of similar age, body mass index (BMI), waist to hip ratio (WHR), and systolic and diastolic blood pressure. In all subjects, the plasma lipoprotein profile and baseline and post-oral glucose tolerance test (OGTT) glucose and insulin plasma values were measured. An intravenous glucose tolerance test was performed and IR was studied by the peripheral insulin sensitivity index (Si). After the OGTT, significantly higher values for insulinemia (at 0, 60, 90, and 120 minutes) and the area under the curve (AUC) of insulin secretion were observed in FCH. The AUC of insulin was greater in FCH subjects with the hypertriglyceridemic phenotype as compared with the controls and significantly lower Si levels, indicating greater IR, were found in the three FCH groups (control, 3.48 +/- 1.87 mU/L/min; FCH IIa, 2.09 +/- 1.08; FCH IIb, 1.54 +/- 0.77; FCH IV, 1.47 +/- 0.93; P < .001). The prevalence of IR (Si < 2 x 10(-4) mU/L/min) was greater in FCH, independent of the lipoprotein phenotype, as compared with the controls (P < .0001). Higher plasma glucose and insulin levels at 120 minutes and lower Si values were found in the FCH IIa group compared with the controls (P < .05), indicating a state of IR in this subgroup of normotriglyceridemic subjects. In conclusion, IR was found in the three FCH lipoprotein phenotypes, being more severe in subjects with hypertriglyceridemia. Hence, the therapeutic goals in FCH should include measures to normalize plasma lipids and improve peripheral insulin sensitivity.

A study of insulin resistance using the minimal model in nondiabetic familial combined hyperlipidemic patients.

The presence of insulin resistance in 20 male nondiabetic patients with familial combined hyperlipidemia (FCH) and 20 controls of similar age and body mass index (BMI) was investigated using the minimal model method modified by the administration of insulin and an oral glucose tolerance test. The peripheral sensitivity of insulin, expressed as the insulin sensitivity index (Si), was 1.91+/-1.05 and 2.86+/-1.19 x 10(-4) x min(-1) x mU/L in FCH patients and controls, respectively (P < .01), and the corresponding value for the peripheral utilization of glucose independently of insulin (Sg) was 1.70+/-1.13 in FCH patients and 2.35+/-0.60 x 10(-2) x min(-1) in controls (P < .02). In the FCH group, the Si value correlated significantly (P < .05) with the waist to hip ratio (WHR), plasma triglycerides (TG), free fatty acids (FFA), and the area under the curve of glucose (AUCg) and insulin (AUCi). In the control group, the correlation also reached statistical significance (P < .05) with age, BMI, WHR, blood pressure, TG, AUCg, and AUCi. Subgrouping the subjects with respect to central obesity defined as a WHR of 0.95 or greater, we observed lower Si values in obese and non-obese FCH subjects relative to controls (P < .02). The mean Si value in obese subjects was significantly lower than in non-obese FCH subgroups (1.40+/-0.79 v 2.68+/-0.95 x 10(-4) x min(-1) x mU/L, respectively, P < .01). In conclusion, a higher degree of insulin resistance relative to control values appears to be an integral part of the metabolic derangements observed in FCH, and central-trunk obesity exacerbates the insulin resistance syndrome.

[Changes in insulin secretion in familial combined hyperlipemia]. / Alteración de la secreción de insulina en la hiperlipemia familiar combinada.

BACKGROUND: We have studied the abnormalities in glucose and insulin metabolism in a group of nondiabetic subjects with familial combined hyperlipidemia (FCH) in order to ascertain the contribution of metabolic risk factors to the elevated coronary heart disease incidence observed in FCH. PATIENTS AND METHODS: The study includes 42 non-diabetic subjects (25 male and 17 women, mean age 49.1 +/- 9.3 years), diagnosed with FCH by clinical and analytical studies of the probands and first degree relatives. Forty two control subjects of similar age, sex and body weight were also studied. In both groups plasma lipids and lipoproteins, plasma glucose and insulin basal and after oral glucose tolerance test (OGTT) were studied. RESULTS: The mean age, BMI and the separation by gender was similar in the two groups. The mean systolic and diastolic blood pressures were higher (p < 0.01) in the FCH group compared with controls (145.4/90.1 and 131.5/76.3 mmHg, respectively). The levels of lipids and apo B were also higher in the FCH group. The plasma glucose values were significantly higher at 30, 60, 90 and 120 minutes during OGTT and the plasma insulin at 0, 60, 90 and 120 minutes of OGTT in FCH respect to controls. The area under the curve of the secretion of insulin was 11652.0 +/- 2281.1 and 7205.4 +/- 2289.1 pmol/l/min in FCH and controls (p < 0.01), respectively. The percentage of subjects with basal hyperinsulinemia was 66.6% in the FCH group and 9.5% in the controls (p < 0.01); at 2 hours OGTT, 78.5% and 9.5% in FCH and controls, respectively (p <0.01). The insulin secretion was significantly related with the plasma triglycerides levels, cholesterol bourded to very low density lipoproteins and systolic and diastolic blood pressure. CONCLUSIONS: Hyperinsulinism is a frequent finding in non-diabetic subjects with FCH, both with normal and abnormal glucose tolerance and could contribute to the high incidence of cardiovascular risk in these patients.

Effects of marathon running on plasma total homocysteine concentrations.

AIMS: There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24h before and after a marathon race. METHODS AND RESULTS: Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23-49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed. RESULTS: Changes in plasma folate and plasma vitamin B12 concentrations were not detected post-race, but a significant increase in plasma tHcy concentrations was demonstrated. Plasma tHcy increased 19% 24h after the race. Before the race 20% of the subjects had a plasma tHcy concentration > 10 micromol/l (cut-off point for ischaemic heart disease risk), while after the race 50% had plasma tHcy concentrations> 10 micromol/l. CONCLUSION: An increase in plasma tHcy concentrations was observed after a marathon race in non-professional not well-trained male athletes performing strong physical activity. The potential physiological or pathological implications of this finding are unknown.

[Hypertriglyceridemia and plasma insulin in combined familial hyperlipidemia]. / Hipertrigliceridemia e insulina plasmática en la hiperlipidemia familiar combinada.

UNLABELLED: Changes in insulin secretion were investigated in a group of non obese subjects with combined familial hyperlipidemia (CFH), with normal glucose tolerance, relating the observed changes with plasma triglycerides and lipoprotein phenotype. MATERIALS AND METHODS: The study was conducted with 21 subjects (16 males and 5 females; mean age: 45.9 +/- 9.1 years), diagnosed of CFH after the clinical and analytical study of patients and their first degree relatives (9 with phenotype IIa, 8 IIb, and 4 IV) and 21 healthy control subjects, of similar age, sex and body weight. In both groups, lipids, plasma lipoproteins, glucose, basal plasma insulin, and insulin after and oral glucose overload (OGO) were quantitated. RESULTS: Diastolic blood pressure was higher (p < 0.01) in CFH group compared with controls (means: 132/80 vs 123/71 mmHg, respectively). TC, TG and Apo B were also higher in the CFH group. With OGO significantly higher serum insulin levels were observed at 0, 30, 60, 90 and 120 minutes in CFH subjects compared with control group. Basal serum insulin and the area under the curve of insulin secretion after OGO was higher in subjects with triglycerides (45,579 +/- 13,056 in controls, 61,385 +/- 22,254 in CFH IIa, 70,645 +/- 17,271 IIb and 124,884 +/- 36,944 in CFH IV. Insulin secretion correlated significantly (p < 0.01) with plasma triglycerides. As conclusion, hyperinsulinism is a finding in CFH non obese subjects and with normal glucose tolerance, and has an increasing frequency in subjects with high triglycerides levels.

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

The influence 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 +/- 8.9 y (45 male, 22 female) defined as obese (BMI > or = 27 kg/m2, n = 39) or non-obese (BMI < 27 kg/m2, 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 > or = 27 kg/m2 had significantly higher systolic and diastolic blood pressure, blood glucose and insulin levels following oral glucose tolerance test than those with BMI < 27 kg/m2. Fasting plasma insulin values were also significantly higher in the BMI > or = 27kg/m2 subjects (138.5 +/- 66.6 vs 111.0 +/- 29.9 pmol/l, respectively, P < 0.05). Quantification of the area under the curve of the insulin secretion showed hyperinsulinaemia in 64.1% of patients with BMI > or = 27kg/m2 compared to 28.5% in the group with BMI < 27 kg/m2 (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 findings in patients with FCH when compared with control subjects of similar age, gender and BMI. Moreover, obesity (BMI > or = 27kg/m2) 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.