Gene expression profile following an oral unsaturated fat load in abdominal obese subjects.

PURPOSE: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. METHODS: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. RESULTS: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. CONCLUSIONS: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.

BACKGROUND: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity. METHODS: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology. RESULTS: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis. CONCLUSIONS: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

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.

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.

[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.

Effect of olive and sunflower oils on low density lipoprotein level, composition, size, oxidation and interaction with arterial proteoglycans.

The atherogenicity of low density lipoproteins (LDL) may be modulated by its serum levels, structure and affinity for components of the intima, all properties that can be altered by diet. Linoleic acid-rich diets (n-G, 18:2) reduce the levels of LDL whereas those rich in oleic (n-9,18:1) are considered 'neutral'. However, LDL enriched in linoleic acid have been reported to be more vulnerable to free radical-mediated oxidation than those enriched in oleic, a potentially atherogenic property. The effect of dietary fats on other properties of LDL that may also modulate atherogenesis, such as size and capacity to interact with intima components, are not well established. We explored here how a change from an olive oil-rich diet (OO) to a sunflower oil-rich one (SFO) affects these parameters in a community with a traditional Mediterranean diet. Eighteen free-living volunteers were placed for 3 weeks on a diet with 31% of caloric intake as sunflower oil and then shifted for an additional 3 weeks to a diet in which OO provided 30.5% of the calories. The LDL after SFO had a fatty acids ratio of (18:2 + 18:3 + 20:4) to (16:0 + 16:1 + 18:0 + 18:1) of 1.06 +/- 0.11 compared to 0.73 +/- 0.06 after the OO period. Serum LDL was significantly lower after SFO than after OO. Unexpectedly, copper-catalyzed oxidation of LDL from the SFO period was significantly less than that of the particles from the OO period. The resistance to oxidation of LDL of the SFO and OO period related to alterations in content of the antioxidants alpha-tocopherol, beta-carotene and retinol, in addition to changes in size and fatty acids composition. In vitro binding of LDL to human arterial proteoglycans was also significantly lower for the SFO-LDL than the OO-LDL, a result that can also be attributed to the larger size of the SFO-LDL. Therefore, three properties of LDL: circulating levels, oxidizability, and affinity with intima proteoglycans, that may modulate its atherogenicity, were shifted in a favorable direction by diets rich in linoleic acid and natural antioxidants.

[Course of cardiac autonomic neuropathy in diabetic patients++ depending on the degree of metabolic control]. / Evolución de la neuropatía autónoma cardíaca en diabéticos según el grado de control metabólico.

Thirty-one diabetic subjects, 19 males and 12 females, with a mean age of 40.5 +/- 14.0 years, 17 of whom were insulin dependent (IDDM) and 14 non-insulin dependent (NIDDM) treated with insulin and diet, were followed for a period of six months. Patients were diagnosed of diabetic autonomic cardiopathy (without other neuropathy causes, nor use of drugs except for insulin) by the alteration of at least 2 of the 5 cardiovascular tests (tCV) performed. Patients underwent an educational diabetes program and self-control, and after 6 months of treatment they were divided into two groups according to the degree of metabolic control. In group 1, in which there was a good control with mean blood sugar levels of 108 +/- 12 mg/dl (5.9 +/- 0.6 mmol/l) and triglycerides of 101 +/- 21 (1.1 +/- 0.2 mmol/l), an improvement in tCV was observed: Valsalva coefficient of 1.16 +/- 0.13 and 1.22 +/- 0.13 (initial and final respectively) (p less than 0.001), with and improvement in 56% of cases; E/I (expiration/inspiration) ratio increased from 1.13 +/- 0.11 to 1.21 +/- 0.11, improving 53% of cases (p less than 0.001); 30/50 index (RR in 30/RR beat in beat 15 after orthostatism) (n.s.); difference in systolic arterial pressure after standing (p less than 0.001) and increase in diastolic arterial pressure with isometric muscular exercise (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Infection in diabetes: the relation to the degree of metabolic control and protein malnutrition]. / Infección en la diabetes: relación con el grado de control metabólico y la malnutrición proteica.

Sixty-one diabetic patients, followed for two years, were divided in two groups for evaluation. One group consisted of the patients who had a bacterial or fungal infection, and the other those in whom no infection had been recorded. The association of the infection with the degree of metabolic control and with the presence or absence of protein malnutrition were assessed. The group of patients with infection was positively correlated with malnutrition and poor metabolic control. In the group with infections, the prevalence of protein malnutrition was 77% while in the patients without infection it was 36%. 11% of patients with sugar blood level lower than 140 mg/dl (7.7 mmol/l) had infections, whereas 79% of those with sugar blood levels higher than 200 mg/dl (11.1 mmol/l) had infections. We emphasize the relevance of hyperglycemia and protein malnutrition as predisposing factors of infection in diabetes and the need to assess the nutritional status in those patients.

[Protein malnutrition in insulin-dependent or type I diabetes mellitus. Relationship with the degree of metabolic control]. / Malnutrición proteica en la diabetes mellitus insulinodependiente o tipo I. Relación con el grado de control metabólico.

Fifty-eight insulin-dependent diabetic (IDDM) patients with a disease duration of more than three years were evaluated and divided in three groups depending on the mean sugar blood levels in a three month follow-up. In the first group sugar blood level was lower than 7.7 mmol/l, in the second group it was between 7.7 and 11.1 mmol/l, and in the third group it was higher than 11.1 mmol/l. The nutritional status was evaluated. Protein malnutrition was found in 50% of the evaluated subjects, with a significant relation between the degree of metabolic control and the prevalence of protein malnutrition. In group I (sugar blood level less than 7.7 mmol/l) the prevalence of malnutrition was 31%, whereas in groups II and III (greater than 7.7 mmol/l) it was 54% and 61%, respectively. We discuss the importance to evaluate the nutritional status in diabetic patients, as protein malnutrition is a significant cause of general morbidity and mortality, which can be added to those attributable to diabetes itself.

[Hyperplasia of the pancreatic islets or nesidioblastosis in adults? Apropos 2 cases]. / Hiperplasia de islotes pancreáticos o nesidioblastosis del adulto? A propósito de dos casos.

Nesidioblastosis is an anatomopathological situation defined as the transformation or the exocrine ductal epithelium into endocrine tissue which can be hormonally active or inactive. In this study we present two cases which to our knowledge fulfil criteria for nesidioblastosis. Both patients were male (73 and 45 years, respectively) who were admitted to our department because they presented hypoglycemia. Blood examination revealed the existence of an hyperinsulinism although axial computerized tomography, pancreatic echocardiography and selective angiography of the celiac arterial trunk failed to demonstrate the presence of the tumor in either of the two cases. Due to the persistence of the clinical picture in the first case and to the intolerance to the diazoxide in the second patient, a subtotal pancreatectomy was performed in both cases. The surgical procedure involved removal of the 80% and 75% of the head and body respectively. Both patients are presently free of symptoms although the first patient in under diazoxide therapy due to persistent hypoglycemia (more spaced crisis).

[Cardiovascular risk factors in patients surviving a myocardial infarction]. / Factores de riesgo cardiovascular en pacientes sobrevivientes a infarto de miocardio.

We studied the risk factors of coronary disease in 52 patients (46 male and 6 female) survivors of myocardial infarction (MI). We found that a group of patients under 40 years old had predominant lipid alteration (100%) being hypercholesterolemia (CT greater than or equal to 260 mg/dl), the decrease of HDL-C levels (less than or equal to 35 mg/dl) and the increase of the atherogenic index (CT/HDL-C greater than or equal to 6) being the most frequent. At the same time, we observed an important association between several risk factors, such as tobacco consumption (58.5%), sedentary life (56.1%), lipid alterations (hypercholesterolemia: 46.3%, decrease of HDL-C: 41.4%, increase of atherogenic index: 60.9%) in the group of patients under 40 years old. These data show that the alterations of lipid metabolism are risk factors frequently observed in young patients with ischemic cardiac disease.