c-peptide and Hypercholesterolemia

To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.. The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52-week placebo-controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post-hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety.. A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL-C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new-onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab- and placebo-treated patients.. Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab- and placebo-treated patients within the glycaemic subgroups examined.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Blood Glucose; C-Peptide; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glycated Hemoglobin; Humans; Hypercholesterolemia; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Treatment Outcome; Triglycerides

To test the efficacy of hormone replacement therapy (HRT) and dietary therapy, compared to dietary therapy, in lowering LDL cholesterol levels among postmenopausal women.. A prospective parallel randomized study of sequential 17 beta-oestradiol and norethisterone acetate or placebo for 48 weeks.. A University outpatient lipid clinic.. A total of 76 postmenopausal women, aged 43-60 years, with LDL cholesterol levels > or = 4.2 mmol 1-1, treated with a lipid-lowering diet.. Levels of lipids, lipoproteins, apolipoproteins, fibrinogen and glucose tolerance.. Adherence to the diet was similar in both groups. Total and LDL cholesterol levels were reduced by 14% (95% CI, 11-17%) and 19% (95% CI, 14-23%), respectively, in the HRT group vs. 3% (95% CI, 0-7%) and 5% (95% CI, 0-11%) in the diet group. HRT reduced the levels of apolipoprotein B and lipoprotein(a). Levels of HDL cholesterol, HDL2, HDL3, triglycerides, lipoprotein populations and apolipoproteins AI and AII remained unchanged. No adverse effects on glucose tolerance or on fibrinogen levels were observed. The reduction in LDL cholesterol was positively correlated with initial levels of LDL cholesterol and negatively correlated with body mass index.. HRT is effective in reducing elevated LDL cholesterol levels, and should be considered in the treatment of hyperlipidaemic postmenopausal women, in addition to dietary therapy.

Topics: Adult; Blood Glucose; C-Peptide; Cholesterol, LDL; Combined Modality Therapy; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hypercholesterolemia; Insulin; Lipids; Middle Aged; Norethindrone; Norethindrone Acetate; Postmenopause; Prospective Studies; Single-Blind Method; Treatment Outcome

Glucose intolerance or diabetes mellitus, hyperlipidemia, obesity and hypertension may have a close interrelation based on insulin resistance. We selected 28 impaired glucose tolerance (IGT) patients with hyperlipidemia. The IGT patients demonstrated hypertriglyceridemia associated with hyperinsulinemia, a typical manifestation of insulin resistance. Administration of bezafibrate at 400 mg/day for 4 weeks to the IGT patients with hypertriglyceridemia resulted in an improvement of the plasma glucose level and insulin response to 75 g oral glucose loading associated with a concomitant decrease in non-esterified fatty acids. The ratio of the level of serum C-peptide to that of insulin after a 75 g oral glucose tolerance test (OGTT) was augmented after 4 weeks of bezafibrate administration. However, reduction of the cholesterol level with pravastatin did not alter these parameters. These results suggest that treatment to reduce the level of serum triglycerides, but not that of cholesterol, may have a beneficial effect for improving insulin resistance even in the non-obese subjects with IGT and decreasing the risk of coronary heart disease.

Topics: Bezafibrate; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypercholesterolemia; Hyperlipidemias; Insulin; Male; Middle Aged; Pravastatin

It has been suggested that the metabolic consequences of a given diet may depend in part on the frequency with which meals are eaten. To investigate the effects of meal frequency on plasma lipid metabolism, 16 free-living hypercholesterolaemic men and women consumed their usual diet as 3 or 9 meals/day in random order for 4 weeks. Dietary macronutrient intake and body weight remained similar on the 2 regimens. Fasting plasma lipids were measured after 2, 3 and 4 weeks on each regimen and there were no significant differences in the fasting concentrations of plasma total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-I and B and the ratio of total: LDL and LDL:HDL cholesterol (HDL-C) on the two diets. The mean (+/- S.D.) fasting total cholesterol was 6.73 +/- 0.74 and 6.81 +/- 0.88 mmol/l on 3 and 9 meals/day, respectively and LDL-C was 4.77 +/- 0.66 and 4.87 +/- 0.78 mmol/l, respectively. There was also no significant variation in the response of plasma triglycerides or serum insulin to a high fat meal following a 3 week adaptation to regimens of 3 and 9 meals/day. Finally the 24 h urinary output of C-peptide was similar on each diet. The consumption of isoenergetic diets as 3 and 9 meals/day did not influence fasting plasma lipid levels, C-peptide excretion or the plasma triglyceride response to a high fat meal of a group of free living hypercholesterolaemic subjects.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Creatinine; Cross-Over Studies; Dietary Fats; Eating; Female; Humans; Hypercholesterolemia; Insulin; Lipids; Male; Middle Aged; Time Factors; Triglycerides

Aim    To study the adipokine profile in young people with hypercholesterolemia and low-density lipoproteins (LDL) and to evaluate the relationship between concentrations of LDL cholesterol (LDL-C) and metabolic hormones in men and women younger than 45 years. Material and methods    This study included 304 subjects (group 1, 56 men with LDL-C concentration <2.1 mmol/l; group 2, 87 men with LDL-C concentration ≥4.2 mmol/l; group 3, 90 women with LDL-C concentration <2.1 mmol/l; and group 4, 71 women with LDL-C concentration ≥4.2 mmol/l). Serum concentrations of total cholesterol (C), triglycerides (TG), high-density lipoprotein C, and glucose were measured by an enzymatic assay with ThermoFisher Scientific kits and a KonelabPrime 30i biochemical analyzer. LDL-C was calculated using the Friedewald's formula. Concentrations of amylin, C-peptide, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), glucagon, interleukin 6, insulin, leptin, monocyte chemotactic protein 1 (MCP-1), pancreatic polypeptide (PP), peptide YY (PYY), tumor necrosis factor alpha (TNF-α), adiponectin, adipsin, lipocalin-2, plasminogen activator inhibitor 1 (PAI-1), and resistin were measured by multiplex analysis (Human Metabolic Hormone V3 and Human Adipokine Panel 1 panels).Results    The groups differed in traditional cardiometabolic risk factors. In the male and female patient groups with LDL-C ≥4.2 mmol/l, the prevalence of impaired fasting glucose, incidence of insulin resistance, TG, and TC were higher than in subjects with LDL-C <2.1 mmol/l. The odds for the presence of LDL hypercholesterolemia (LDL-C ≥4.2 mmol/l) were significantly associated with increased concentrations of C-peptide and lipocalin-2 in men and with increased concentrations of lipocalin-2 and decreased concentrations of GLP-1 in women (р<0.05).Conclusion    Increased concentrations of LDL-C in young people were associated with changes in the adipokine profile and with the presence of metabolic syndrome components. These results were confirmed by changes in blood concentrations of metabolic markers that characterize disorders of metabolic processes.

Topics: Adipokines; Adolescent; C-Peptide; Cholesterol, LDL; Female; Glucagon-Like Peptide 1; Glucose; Humans; Hypercholesterolemia; Hyperlipidemias; Lipocalin-2; Male; Triglycerides

The aim of the presented study is to evaluate metabolic features in adolescents with polycystic ovary syndrome (PCOS) in comparison with age- and BMI-matched subjects. Forty-three adolescents with PCOS according to ESHRE criteria were prospectively evaluated and compared with 48 control subjects. Blood sampling was done in the early follicular phase of menstrual cycle, between 1st and 5th day, for plasma glucose, total and high-density lipoprotein (HDL)-cholesterol, triglycerides, insulin and C peptide. The diagnosis of metabolic syndrome was done according to IDF adolescent criteria. Adolescents with PCOS have increased low-density lipoprotein (LDL)-cholesterol (p < 0.002), decreased HDL-cholesterol (p <0.0007) and increased C peptide levels (p < 0.02) in comparison with healthy adolescents. Total cholesterol, triglycerides, fasting blood glucose, fasting insulin, HOMA-IR, waist-to-hip ratio, systolic and diastolic blood pressure did not differ between the groups. There was no difference when we compared the prevalence of adolescents with at least one feature of metabolic syndrome between PCOS (17 from 43) and healthy controls (27 from 48). In conclusion, adolescents with PCOS have less favourable blood lipid profiles with higher LDL-cholesterol and lower levels of HDL-cholesterol and are more insulin resistant than their healthy counterparts having higher fasting C peptide levels.

Topics: Adolescent; Adult; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Czech Republic; Female; Follicular Phase; Humans; Hypercholesterolemia; Insulin Resistance; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Prevalence; Prospective Studies; Young Adult

We investigated the possible causes of diabetes in a young child who presented with hyperglycemia associated with severe hypertriglyceridemia (>166 mmol/l), hypercholesterolemia (>38 mmol/l) and fasting chilomicrons.. The patient did not have any of the HLA and autoantibody markers typically associated with type 1 diabetes. A glucose clamp failed to demonstrate insulin resistance (peripheral glucose utilization rate (M)=4.3 mg/kg per min) and there was no family history of type 2 diabetes or maturity onset diabetes in youth. Both fasting and stimulated C-peptide levels, including those in response to i.v. glucagon, were below the limit of detection. This is consistent with loss of beta-cell function. The family history did not reveal the existence of relatives with lipid abnormalities, coronary heart disease, and pancreatitis. We did not find any abnormality of plasma apoCII, lipoproteinlipase and hepatic lipase activities. The patients had a epsilon3/epsilon3 apoE genotype and she rapidly cleared an oral fat load after normalization of plasma lipids.. The mild hyperglycemia seems an unlikely explanation for both the severe hypertriglyceridemia and chylomicronemia. A more plausible explanation is transient lipoproteinlipase deficiency. This rare condition, occasionally associated with a high-fat diet, could have caused the rapid and dramatic hypertriglyceridemia observed in this patient, which in turn might have led to the beta-cell destruction by direct lipid toxicity.

Topics: Autoantibodies; Autoimmunity; C-Peptide; Child; Chylomicrons; Diabetes Mellitus, Type 1; Fasting; Female; Glucagon; Glucose Clamp Technique; Humans; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Islets of Langerhans; Lipoprotein Lipase

The objective of the study reported here was to induce obesity in the female Göttingen minipig to establish a model of the human metabolic syndrome. Nine- to ten-month-old female Göttingen minipigs received a high-fat high-energy (HFE) diet or a low-fat, low-energy (LFE) diet. The energy contents derived from fat were 55 and 13 %, respectively. After 5 weeks, animals were subjected to dual energy x-ray absorptiometry (DEXA) scanning, intravenous glucose tolerance testing (IVGTT), and 6-h growth hormone profile recording. After treatment, mean body weight of pigs of the LFE group was 21.0 +/- 0.4 kg, and was 26.8 +/- 0.2 kg in pigs of the HFE group (P < 0.0001). The DEXA scanning indicated that the fat content of the LFE group was 10.0 +/- 1.2 % versus 15.2 +/- 0.7 % in the HFE group (P < 0.003). Triglycerides concentration was significantly (P < 0.05) increased in pigs of the HFE group (0.24 +/- 0.03 mM), compared with that in pigs of the LFE group (0.13 +/- 0.04 mM). Preprandial plasma glucose and insulin concentrations were not affected, but insulin area under the curve during IVGTT was significantly high in the obese animals. Growth hormone (GH) secretion was low in both groups of pigs. The obese minipig shares some of the metabolic impairments seen in obese humans, and may thus serve as a model of the metabolic syndrome.

Topics: Absorptiometry, Photon; Animals; Area Under Curve; Blood Glucose; C-Peptide; Diet, Fat-Restricted; Dietary Fats; Disease Models, Animal; Fasting; Female; Fructosamine; Glucose Tolerance Test; Growth Hormone; Humans; Hypercholesterolemia; Hypertriglyceridemia; Insulin; Insulin Secretion; Insulin-Like Growth Factor I; Lipids; Metabolic Syndrome; Obesity; Pituitary Gland, Anterior; Species Specificity; Swine, Miniature

The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001).. Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio.. In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Topics: Administration, Oral; Adult; Age Factors; Aged; Albuminuria; Blood Glucose; Body Constitution; Body Mass Index; C-Peptide; Comorbidity; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Hyperinsulinism; Hypertension; Hypertriglyceridemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Italy; Male; Middle Aged; Obesity; Prevalence; Risk Factors