Insulin detemir for the treatment of obese patients with type 2 diabetes

The risk for developing type 2 diabetes (T2DM) is greater among obese individuals. Following onset of the disease, patients with T2DM become more likely to be afflicted with diabetic micro- and macrovascular complications. Decreasing body weight has been shown to lower glycosylated hemoglobin and improve other metabolic parameters in patients with T2DM. Medications used to lower blood glucose may increase body weight in patients with T2DM and this has been repeatedly shown to be the case for conventional, human insulin formulations. Insulin detemir is a neutral, soluble, long-acting insulin analog in which threonine-30 of the insulin B-chain is deleted, and the C-terminal lysine is acetylated with myristic acid, a C14 fatty acid chain. Insulin detemir binds to albumin, a property that enhances its pharmacokinetic/pharmacodynamic profile. Results from clinical trials have demonstrated that treatment with insulin detemir is associated with less weight gain than either insulin glargine or neutral protamine Hagedorn insulin. There are many potential reasons for the lower weight gain observed among patients treated with insulin detemir, including lower risk for hypoglycemia and therefore decreased defensive eating due to concern about this adverse event, along with other effects that may be related to the albumin binding of this insulin that may account for lower within-patient variability and consistent action. These might include faster transport across the blood–brain barrier, induction of satiety signaling in the brain, and preferential inhibition of hepatic glucose production versus peripheral glucose uptake. Experiments in diabetic rats have also indicated that insulin detemir increases adiponectin levels, which is associated with both weight loss and decreased eating

Insulin degludec improves long-term glycaemic control similarly to insulin glargine but with fewer hypoglycaemic episodes in patients with advanced type 2 diabetes on basal-bolus insulin therapy.

The aim of the present study was to compare the long-term safety and efficacy of insulin degludec with those of insulin glargine in patients with advanced type 2 diabetes (T2D) over 78 weeks (the 52-week main trial and a 26-week extension). Patients were randomized to once-daily insulin degludec or insulin glargine, with mealtime insulin aspart ± metformin ± pioglitazone, and titrated to pre-breakfast plasma glucose values of 3.9-4.9 mmol/l (70-88 mg/dl). After 78 weeks, the overall rate of hypoglycaemia was 24% lower (p = 0.011) and the rate of nocturnal hypoglycaemia was 31% lower (p = 0.016) with insulin degludec in the extension trial set, while both groups of patients achieved similar glycaemic control. Rates of adverse events and total insulin doses were similar for both groups in the safety analysis set. During 18 months of treatment, insulin degludec + mealtime insulin aspart ± oral antidiabetic drugs in patients with T2D improves glycaemic control similarly, but confers lower risks of overall and nocturnal hypoglycaemia than with insulin glargine treatment

Importance of early insulin secretion. Comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes

WSTĘP. Badanie przeprowadzono w celu porównania wpływu nateglinidu, gliburydu i placebo na poposiłkowe zwyżki glikemii oraz wydzielanie insuliny u chorych na cukrzycę typu 2 leczonych uprzednio dietą. MATERIAŁ I METODY. Badanie przeprowadzono metodą podwójnie ślepej próby, z udziałem grupy kontrolnej. Randomizacją objęto 152 chorych z kilku ośrodków. Otrzymywali oni przez 8 tygodni nateglinid (120 mg przed posiłkiem 3 razy dziennie, n = 51) lub gliburyd (5 mg 4 razy dziennie, po 2 tygodniach dawkę zwiększano do 10 mg 4 razy dziennie, n = 50) lub placebo (n = 51). Tydzień przed rozpoczęciem badania oraz po 8 tygodniach leczenia wykonywano oznaczenie profilu glikemii, insulinemii oraz stężenia peptydu C po prowokacji w postaci pokarmów płynnych. Tydzień przed badaniem oraz po 7 tygodniach terapii na podstawie 19 pomiarów określano dzienny profil glikemii i insulinemii. Chorzy spożywali w ciągu tego okresu 3 posiłki stałe. WYNIKI. Po spożyciu pokarmów płynnych nateglinid skuteczniej zmniejszał przyrostowe pole pod krzywą (AUC, area under the curve) dla glukozy niż gliburyd (D = -4,94 vs. -2,71 mmol &#8226; h/l, p < 0,05), zaś gliburyd skuteczniej niż nateglinid obniżał stężenie glukozy w osoczu na czczo (D = -2,9 vs. -1,0 mmol/l, p < 0,001). Natomiast wzrost stężenia peptydu C wywołany przez gliburyd był większy niż w przypadku nateglinidu (D = +1,83 vs. +0,95 nmol &#8226; h/p < 0,01) i jedynie gliburyd zwiększał stężenie insuliny na czczo. Po prowokacji w formie pokarmów stałych zarówno nateglinid, jak i gliburyd zapewniały podobną całkowitą kontrolę glikemii (D 12-h AUC przyrostowe = -13,2 vs. -15,3 mmol &#8226; h/l), lecz AUC dla insuliny w przypadku nateglinidu było wyraźnie mniejsze niż w przypadku gliburydu (D 12-h AUC = +866 vs. +1702 pmol &#8226; h/l, p = 0,01). WNIOSKI. Badanie to wykazało, że nateglinid wybiórczo zwiększał wczesne wydzielanie insuliny i zapewniał lepszą kontrolę glikemii w czasie spożywania posiłków niż gliburyd, powodując jednocześnie mniejszą całkowitą ekspozycję na insulinę niż gliburyd.INTRODUCTION. This study compared the effects of nateglinide, glyburide, and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS. This randomized, double-blind, placebo-controlled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n = 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51) for 8 weeks. Glucose, insulin, and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8. At weeks &#8212; 1 and 7, 19-point daytime glucose and insulin profiles, comprising three solid meals, were measured. RESULTS. During the liquid-meal challenge, nateglinide reduced the incremental glucose area under the curve (AUC) more effectively than glyburide (D = &#8211;4.94 vs. &#8211;2.71 mmol &#8226; h/l, p < 0.05), whereas glyburide reduced fasting plasma glucose more effectively than nateglinide (D = &#8211;2.9 vs. &#8211;1.0 mmol/l, respectively, p < 0.001). In contrast, C-peptide induced by glyburide was greater than that induced by nateglinide (D = +1.83 vs. +0.95 nmol &#8226; h/l, p < 0.01), and only glyburide increased fasting insulin levels. During the solid meal challenges, nateglinide and glyburide elicited similar overall glucose control (D 12-h incremental AUC = &#8211;13.2 vs. &#8211;15.3 mmol &#8226; h/l), but the insulin AUCinduced by nateglinide was significantly less than that induced by glyburide (D 12-h AUC = +866 vs. +1,702 pmol &#8226; h/l, p = 0.01). CONCLUSIONS. This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide

Prognostic impact of abdominal lymph node involvement in diffuse large B-cell lymphoma

OBJECTIVE: The prognostic value of site of nodal involvement in diffuse large B-cell lymphomas (DLBCL) is mainly unknown. We aimed to determine the prognostic significance of nodal abdominal involvement in relation to tumour cell markers and clinical characteristics of 249 DLBCL patients in a retrospective single-centre study. METHODS: Contrast-enhanced computed tomography (CT) of the abdomen and thorax revealed pathologically enlarged abdominal lymph nodes in 156 patients, while in 93 patients there were no pathologically enlarged lymph nodes in the abdomen. In 81 cases, the diagnosis of DLBCL was verified by histopathological biopsy obtained from abdominal lymph node. RESULTS: Patients with abdominal nodal disease had inferior lymphoma-specific survival (P = .04) and presented with higher age-adjusted IPI (P &lt; .001), lactate dehydrogenase (P &lt; .001) and more often advanced stage (P &lt; .001), bulky disease (P &lt; .001), B symptoms (P &lt; .001), and double expression of MYC and BCL2 (P = .02) compared to patients without nodal abdominal involvement, but less often extranodal involvement (P &lt; .02). The worst outcome was observed in those where the abdominal nodal involvement was verified by histopathological biopsy. CONCLUSION: Diffuse large B-cell lymphomas patients with abdominal nodal disease had inferior outcome and more aggressive behaviour, reflected both in clinical and biological characteristics

Proteomic analysis of the plasma membrane-movement tubule complex of cowpea mosaic virus

Cowpea mosaic virus forms tubules constructed from the movement protein (MP) in plasmodesmata (PD) to achieve cell-to-cell movement of its virions. Similar tubules, delineated by the plasma membrane (PM), are formed protruding from the surface of infected protoplasts. These PM-tubule complexes were isolated from protoplasts by immunoprecipitation and analysed for their protein content by tandem mass spectrometry to identify host proteins with affinity for the movement tubule. Seven host proteins were abundantly present in the PM-tubule complex, including molecular chaperonins and an AAA protein. Members of both protein families have been implicated in establishment of systemic infection. The potential role of these proteins in tubule-guided cell-cell transport is discussed.</p

Similar Efficacy and Safety of Basaglar® and Lantus® in Patients with Type 2 Diabetes in Age Groups (<65 Years, ≥65 Years): A Post Hoc Analysis from the ELEMENT-2 Study

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> (<a href="https://link.springer.com/article/10.1007/s13300-018-0405-5">https://link.springer.com/article/10.1007/s13300-018-0405-5</a>).</p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p> </p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p