Te recuerdo Amanda (y Antonio J.) / I remember you Amanda (and Antonio J.)

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Development of a new fear of hypoglycemia scale: FH-15.

Hypoglycemia is the most common adverse event associated with insulin treatment in diabetes. The consequences of hypoglycemia can be quite aversive and potentially life threatening. The physical sequelae provide ample reason for patients to fear hypoglycemia and avoid episodes. For these reasons, our purpose in this study was to develop a new measure that explores specific fear of hypoglycemia (FH) in adult patients with type 1 diabetes and to examine its psychometric properties. The instrument developed to assess FH was initially made up of 20 items, of which 18 were negative and 2 were positive, assessed on a 5-point Likert scale (1-5). This scale was completed by 229 patients with type 1 diabetes. Additionally, a structured interview and a closed question called subjective fear of hypoglycemia were included as diagnostic criteria. A factor analysis employing the principal-components method and promax rotation was carried out, resulting in a new scale composed of 15 items. Three factors (fear, avoidance, and interference) were obtained and explained 58.27% of the variance. The scale showed good internal consistency (Cronbach's α = .891) and test-retest reliability (r = .908, p < .001), as well as adequate concurrent and predictive validity. The cutoff score that provided the highest overall sensitivity and specificity was set at 28 points. The Fear of Hypoglycemia 15-item scale (FH-15) demonstrated good reliability and validity. This study suggests that the new instrument may serve as a valuable measure of specific FH for use in research and clinical practice.

Effects of milk enriched with omega-3 fatty acid, oleic acid and folic acid in patients with metabolic syndrome.

BACKGROUND & AIMS: Patients with metabolic syndrome (MS) have increased cardiovascular risk factors. Dietary modifications mainly polyunsatturated fatty acids intake, can improve them. The present study was performed to assess the effects of enriched milk with omega-3 and oleic fatty acids, folic acid and vitamin E, in these patients. METHODS: We performed a randomized, placebo-controlled and open clinical trial, among 72 patients with MS for 3 months. Thirty-six of them consumed 500 cm(3) per day of semi-skimmed milk (control group), and the others consumed 500 cm(3) per day of enriched milk (test group). Daily supplements in this group were 5.7 g of oleic acid, 0.2g of omega-3 fatty acid, 150 microg of folic acid and 7.5mg of vitamin E. Serum for total and HDL cholesterol, triglycerol, Apo B, glucose, insulin, hs-CRP, homocysteine and fatty acids contents in serum phospholipids, was obtained at the beginning and at the end of the study. LDL cholesterol was calculated by Friedewald formula. RESULTS: Four patients in the test group, and two in the control group dropped out. In the test group a decrease in serum total cholesterol (-6.2%, P=0.006), LDL cholesterol (-7.5%, P=0.032), triglycerol (-13.3%, P=0.016), Apo B (-5.7%, P=0.036), glucose (-5.3%, P=0.013), and homocysteine (-9.5%, P=0.00) was observed. Any of these parameters changed in the control group. CONCLUSIONS: Dietary supplementation with 500 cm(3) of enriched milk with omega-3 fatty acid, oleic acid and folic acid, reduces serum tryglicerides, total and LDL cholesterol, Apo B, glucose and homocysteine in patients with MS. This milk is well tolerated and accepted by the patients.

Structure-function analysis of the alpha5 and the alpha13 helices of human glucokinase: description of two novel activating mutations.

It was recently described that the alpha5 and the alpha13 helices of human pancreatic glucokinase play a major role in the allosteric regulation of the enzyme. In order to understand the structural importance of these helices, we have performed site-directed mutagenesis to generate glucokinase derivatives with altered residues. We have analyzed the kinetic parameters of these mutated forms and compared them with wild-type and previously defined activating mutations in these helices (A456V and Y214C). We found two new activating mutations, A460R and Y215A, which increase the affinity of the enzyme for glucose. Our results suggest that substitutions in the alpha5 or the alpha13 helices that favor the closed, active conformation of the enzyme, either by improving the interaction with surrounding residues or by improving the flexibility of the region defined by these two helices, enhance the affinity of the enzyme for glucose, and therefore its performance as a glucose phosphorylating enzyme.

Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation.

Glucokinase (GK) is a glycolytic key enzyme that functions as a glucose sensor in the pancreatic beta-cell, where it governs glucose-stimulated insulin secretion (GSIS). Heterozygous inactivating mutations in the glucokinase gene (GCK) cause a mild form of diabetes (maturity-onset diabetes of the young [MODY]2), and activating mutations have been associated with a mild form of familial hyperinsulinemic hypoglycemia. We describe the first case of severe persistent hyperinsulinemic hypoglycemia due to a "de novo" mutation in GCK (Y214C). A baby girl presented with hypoglycemic seizures since the first postnatal day as well as with inappropriate hyperinsulinemia. Severe hypoglycemia persisted even after treatment with diazoxide and subtotal pancreatectomy, leading to irreversible brain damage. Pancreatic histology revealed abnormally large and hyperfunctional islets. The mutation is located in the putative allosteric activator domain of the protein. Functional studies of purified recombinant glutathionyl S-transferase fusion protein of GK-Y214C showed a sixfold increase in its affinity for glucose, a lowered cooperativity, and increased kcat. The relative activity index of GK-Y214C was 130, and the threshold for GSIS predicted by mathematical modeling was 0.8 mmol/l, compared with 5 mmol/l in the wild-type enzyme. In conclusion, we have identified a de novo GCK activating mutation that causes hyperinsulinemic hypoglycemia of exceptional severity. These findings demonstrate that the range of the clinical phenotype caused by GCK mutations varies from complete insulin deficiency to extreme hyperinsulinemia.