Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart

WSTĘP. Insulina detemir jest rozpuszczalnym, długodziałającym analogiem insuliny. Cechuje się wyjątkowym, wydłużonym profilem działania, pozwalającym na zmniejszenie zmienności glikemii, związanej ze stosowaniem konwencjonalnych insulin długodziałających. W badaniu porównano insulinę detemir i insulinę NPH pod względem uzyskanej kontroli glikemii, ryzyka hipoglikemii oraz wpływu na masę ciała u chorych na cukrzycę typu 1, otrzymujących przedposiłkowe wstrzyknięcia insuliny krótkodziałającej aspart. MATERIAŁ I METODY. Do badania zakwalifikowano metodą randomizacji 448 chorych na cukrzycę typu 1, którym podawano insulinę detemir lub NPH w stosunku 2:1. Badanie typu otwartego, w którym porównywano równolegle obie grupy pacjentów, trwało 6 miesięcy i było prowadzone w 46 ośrodkach, w 5 krajach. WYNIKI. Po 6 miesiącach badania wartości hemoglobiny glikowanej (HbA1c) w obu grupach były porównywalne. Glikemia na czczo była nieco niższa u chorych leczonych insuliną detemir, jednak różnica ta nie była istotna statystycznie (&#8211;0,76 mmol/l; p = 0,097). Zmienność glikemii na czczo określana na podstawie samokontroli u poszczególnych pacjentów była mniejsza przy stosowaniu insuliny detemir niż insuliny NPH (SD 3,37 vs. 3,78 mmol/l; p < 0,001). Ryzyko niedocukrzenia było o 22% niższe w grupie leczonej insuliną detemir niż w grupie przyjmującej insulinę NPH (p < 0,05); a ryzyko nocnych niedocukrzeń (23.00-06.00) &#8212; o 34% niższe (p < 0,005). Profil glikemii w porze nocnej był bardziej stabilny i stały podczas stosowania insuliny detemir (p = 0,05). Na końcu badania u pacjentów leczonych insuliną detemir zaobserwowano istotnie niższą masę ciała (p < 0,001). WNIOSKI. Leczenie insuliną detemir wiąże się z bardziej przewidywalną kontrolą glikemii, z mniejszymi wahaniami glikemii w ciągu doby oraz istotnym zmniejszeniem ryzyka niedocukrzeń w porównaniu ze stosowaniem insuliny NPH. Zmniejszenie masy ciała podczas terapii insuliną detemir jest dodatkowym, potencjalnie korzystnym efektem. Schematy leczenia oparte na insulinie detemir mogą umożliwić lepszą kontrolę glikemii niż schematy oparte na insulinie NPH.INTRODUCTION. Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. MATERIAL AND METHODS. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS. After 6 months, comparable HbA1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (&#8211;0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300&#8211;0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P < 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001). CONCLUSIONS. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin

Insulin Detemir in the Treatment of Type 1 and Type 2 Diabetes

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia) in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime). Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients

Linkage study of fibrinogen levels: the Strong Heart Family Study

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.8 fold for 1 g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations.</p> <p>Methods</p> <p>The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program.</p> <p>Results</p> <p>Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28 cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (<it>STAT3</it>), were identified within 2 and 8 Mb of this 1 LOD drop interval respectively. A LOD score of 1.82 on chromosome 17 between 68 and 93 cM is supported by reports from two other populations with LOD scores of 1.4 and 1.95.</p> <p>Conclusion</p> <p>In a minority population with a high prevalence of cardiovascular disease, strong evidence for a novel genetic determinant of fibrinogen levels is found on chromosome 7 at 28 cM. Four other loci, some of which have been suggested by previous studies, were also identified.</p

Nécrologie: Bernardo Alberto Houssay 1887-1971

Obituario que describen las características de la personalidad de Houssay, se refiere a sus orígenes, enumera los hallazgos científicos realizados en colaboración con los numerosos estudiantes que formó, durante una obra de más cincuenta años de trabajo, resalta el impacto que le ocasionó al autor el equilibrio de la personalidad del Nobel. Menciona a la familia, las distinciones y premios que obtuvo Houssay, compartiendo desde la Sociedad de Endocrinología francesa, el dolor por su fallecimiento.Fil: Vague, Jean. French Society of Endocrinology; FranciapapelKofax Power v.3.1Fujitsu ScanSnap SV600DIR-7BAH-BioUnidad documental simpleIBYME-Biblioteca Bernardo A. Houssay-0

Predicting factors of hypoglycaemia in elderly type 2 diabetes patients: Contributions of the GERODIAB study

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores