EFFECTS OF AN ACUTE INCREASE IN PLASMA TRIGLYCERIDE LEVELS ON GLUCOSE-METABOLISM IN MAN

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2. Opposite results were found for lipid oxidation, which remained unchanged during test 1 as compared with the control period but significantly decreased during tests 2 and 3. Hepatic glucose production was less inhibited during test 1 than during tests 2 and 3, and less so during test 2 than test 3. In conclusion, at least under these particular conditions, acute hypertriglyceridemia induced by Intralipid infusion seems to decrease forearm glucose uptake, glucose oxidation, and insulin-induced suppressibility of hepatic glucose production. Taking our results together, it seems that the triglyceride effect on carbohydrate metabolism occurs via triglyceride hydrolysis using the intracellular pathways of FFA without interference with the circulating FFA pool

Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting

Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting

In vitro starch digestibility and in vivo glucose response of gluten free foods and their gluten counterparts

Background. Recently there has been increasing interest in the production of gluten-free (GF) foods and studies on minor cereals and pseudocereals without celiac activity in order to fulfill the specific needs of people affected by celiac disease. GF bread, pasta, biscuits are usually manufactured using different combinations of thickenings and particular food processing procedures, that could affect starch digestibility. Carbohydrates, mainly starch from cereals, play an important part a balanced diet, and dietary guidelines suggest a diet with low glycemic index foods, that is to say rich in slowly digested carbohydrates. Aim. The present study was aimed at evaluating: (1) the importance of some GF food characteristics in relation to their effects on in vitro starch accessibility to digestion, in comparison with traditional gluten products; (2) the in vivo metabolic responses to GF foods. Methods. Firstly, starch digestibility of several products was evaluated in vitro. Then, an in vivo study was performed on a group of healthy volunteers. Postprandial glucose and insulin responses were evaluated after administration of three GF foods and traditional bread. Triglycerides and free fatty acids (FFA) were also evaluated. Attempts were also made to explore differences in metabolic responses to GF foods in healthy subjects with respect to celiac subjects. Results. The area under the curve (AUC) of digested starch of GF bread was slightly higher than that of the traditional counterpart. No significant difference was observed in AUCs of digested starch between GF pasta and the traditional pasta. The AUCs of digested starch of quinoa and the two samples of pasta were not statistically different. Significant differences were observed between GF bread and bread-like products. Statistic differences in glucose responses to GF pasta were observed between healthy and celiac subjects. In healthy subjects, the AUCs of glucose response after GF bread were higher than that after bread with gluten. No significant differences were observed between the AUCs of insulin responses to all products tested. Glycemic index (GI) for GF pasta was similar to GI for GF bread while GI for quinoa was slightly lower than that of GF pasta and bread. Two-way ANOVA revealed that quinoa induced lower FFA levels with respect to GF pasta. In addition, triglyceride concentrations were significantly reduced for quinoa with respect to GF bread and bread. Conclusions. Our results indicate that the different formulations and the food processing procedures used in the manufacturing of GF products may affect the rate of starch digestion both in vitro and in vivo. It may be worthwhile improving the formulation of these products. Furthemore, quinoa seem to represent a potential alternative to traditional foods, even if further and larger studies are required to demonstrate its hypoglycemic effects

Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes

OBJECTIVE - To test the hypothesis that selected abnormalities cluster in type 2 diabetic families. Offspring of patients with type 2 diabetes have a 40-60% chance of developing type 2 diabetes and an increased frequency of impaired glucose tolerance (IGT) or unknown diabetes. These offspring also show metabolic abnormalities of type 2 diabetes, such as insulin resistance, high insulin and pro-insulin, low HDL cholesterol levels, arterial hypertension, and microalbuminuria. RESEARCH DESIGN AND METHODS - We studied 87 families including at least one type 2 diabetic patient, i.e., 87 probands and 146 siblings; 60 spouses of probands with no family history of diabetes were compared with siblings. Familial clustering was evaluated by 2 methods: concordance of siblings and probands for a given abnormality (method 1) and intraclass correlation coefficients of values within each family (method 2). RESULTS - At oral glucose tolerance testing, 24 siblings had type 2 diabetes, 31 siblings had IGT, and 14 spouses had IGT (P = 0.0012 vs. siblings). With method 1, familial clustering occurred for microalbuminuria, insulin resistance, arterial hypertension, HDL cholesterol and pro-insulin levels; with method 2, familial clustering was observed for the same variables except for microalbuminuria. With both method 1 and 2, familial clustering for insulin resistance disappeared, whereas familial clustering for arterial bloodpressure, HDL cholesterol, and pro-insulin remained after correction for BMI; after further restriction of analysis to probands and to siblings with normal glucose tolerance, familial clustering for pro-insulin was observed only with method 2. CONCLUSIONS - These data indicate that siblings of diabetic patients are at high risk for selected features of type 2 diabetes

Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation

The aim of the study was to evaluate whether the cephalic phase of insulin release is still present in patients submitted to simultaneous kidney and pancreas transplantation. Subjects were five kidney-pancreas-transplanted patients (group P) and five control (group C). The experimental protocol lasted 30 minutes, and blood samples were collected at 1-minute intervals. After a 20-minute period of steady-state fasting (premeal period), subjects received a palatable standard meal (pizza). Samples were collected over the subsequent 10 minutes (meal period). No evidence of an increase in serum free insulin, serum C-peptide, and plasma glucagon during food ingestion was observed in group P whereas the test was effective in eliciting cephalic-phase insulin and glucagon release in group C. Gastric inhibitory polypeptide and somatostatin did not show any variation during the test in both groups. In conclusion, the absence of cephalic-phase insulin and glucagon release in group P could be explained by denervation of the grafted pancreas. This early alteration could contribute to the impairment in glucose tolerance frequently observed in successfully pancreas-transplanted patients

Respiratory fatigue in patients with acute cardiogenic pulmonary edema.

Evaluation of prevalence and features of respiratory fatigue (RF) in patients with acute cardiogenic pulmonary oedema (APE) Eighteen patients out of 65 consecutive APE were enrolled. All were treated with CPAP delivered by helmet added to medical therapy. RF (defined as an arterial CO 2 tension at admission higher than the expected) was diagnosed in nine patients. In these patients pH was lower (7.18 vs 7.35; P = 0.0001), base excess more negative (-9.9 vs -3.7 mEq/l; P = 0.005) and blood lactates more elevated (46.4 vs 20.8 mg/dl; P = 0.013) than in non-fatigued patients; after 3 h of treatment no more differences were found between the two groups. At admission RF patients had lower mean echocardiographic left ventricular ejection fraction (LVEF): 30.7 ± 12.4% vs 39.1 ± 12.8%. After 24 h LVEF increased significantly (P = 0.0034) in RF patients, whereas didn't in non-fatigued ones (P = 0.19). About 50% of patients with APE present respiratory fatigue. These patients are characterized by a pH <7.3 at admission; they are likely to rapidly restore normal gas exchange when treated with CPAP, and to have their LVEF improved after APE resolutio

In middle-aged siblings of patients with type 2 diabetes mellitus normal glucose tolerance is associated with insulin resistance and with increased insulin secretion : The SPIDER study

Objectives: To evaluate the frequency of impaired glucose tolerance (IGT) and of Type 2 diabetes mellitus (Type 2 DM) in siblings of patients with Type 2 DM, and to assess insulin release and insulin sensitivity in siblings with normal glucose tolerance (NGT), compared with NGT spouses of probands without family history of Type 2 DM. Design and Methods: We evaluated 87 families including 103 Type 2 DM patients (87 probands), and we carried out an oral glucose tolerance test (OGTT) in 130 siblings and in 60 spouses. Among NGT subjects, 12 siblings and 16 spouses underwent a low-dose insulin-glucose infusion test (LDIGIT) to evaluate C-peptide release and insulin sensitivity. Results: After the OGTT, 24 siblings were classified as having Type 2 DM, 31 as IGT, and only 14 spouses as IGT (P = 0.0012 vs siblings). NGT siblings (n = 75) showed higher insulin levels at 120 min than NGT spouses (n = 46) at OGTT, in spite of identical blood glucose levels; at LDIGIT, NGT siblings secreted more C-peptide and showed a lower insulin sensitivity than NGT spouses. Conclusions: These data indicate that middle-aged siblings of probands with Type 2 DM have a high frequency of IGT and Type 2 DM, and that NGT siblings have increased insulin resistance and increased insulin secretion when compared with adequate controls