Vildagliptin therapy reduces postprandial intestinal triglyceride-rich lipoprotein particles in patients with type 2 diabetes

Peer reviewe

Drift-dependent changes in iceberg size-frequency distributions

Although the size-frequency distributions of icebergs can provide insight into how they disintegrate, our understanding of this process is incomplete. Fundamentally, there is a discrepancy between iceberg power-law size-frequency distributions observed at glacial calving fronts and lognormal size-frequency distributions observed globally within open waters that remains unexplained. Here we use passive seismic monitoring to examine mechanisms of iceberg disintegration as a function of drift. Our results indicate that the shift in the size-frequency distribution of iceberg sizes observed is a product of fracture-driven iceberg disintegration and dimensional reductions through melting. We suggest that changes in the characteristic size-frequency scaling of icebergs can be explained by the emergence of a dominant set of driving processes of iceberg degradation towards the open ocean. Consequently, the size-frequency distribution required to model iceberg distributions accurately must vary according to distance from the calving front

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

LETTERS TO THE EDITOR

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65729/1/j.1752-7325.1980.tb01869.x.pd

Immunohistochemical Characterisation of GLUT1, MMP3 and NRF2 in Osteosarcoma.

Osteosarcoma (OSA) is an aggressive bone malignancy. Unlike many other malignancies, OSA outcomes have not improved in recent decades. One challenge to the development of better diagnostic and therapeutic methods for OSA has been the lack of well characterized experimental model systems. Spontaneous OSA in dogs provides a good model for the disease seen in people and also remains an important veterinary clinical challenge. We recently used RNA sequencing and qRT-PCR to provide a detailed molecular characterization of OSA relative to non-malignant bone in dogs. We identified differential mRNA expression of the solute carrier family 2 member 1 (SLC2A1/GLUT1), matrix metallopeptidase 3 (MMP3) and nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2) genes in canine OSA tissue in comparison to paired non-tumor tissue. Our present work characterizes protein expression of GLUT1, MMP3 and NRF2 using immunohistochemistry. As these proteins affect key processes such as Wnt activation, heme biosynthesis, glucose transport, understanding their expression and the enriched pathways and gene ontologies enables us to further understand the potential molecular pathways and mechanisms involved in OSA. This study further supports spontaneous OSA in dogs as a model system to inform the development of new methods to diagnose and treat OSA in both dogs and people

Genetic variation in stromal proteins decorin and lumican with breast cancer: investigations in two case-control studies.

INTRODUCTION: The stroma is the supportive framework of biologic tissue in the breast, consisting of various proteins such as the proteoglycans, decorin and lumican. Altered expression of decorin and lumican is associated with breast tumors. We hypothesized that genetic variation in the decorin (DCN) and lumican (LUM) genes may contribute to breast cancer. METHODS: We investigated associations of 14 common polymorphisms in the DCN and LUM genes with 798 breast cancer cases and 843 controls from Mayo Clinic, MN, USA. One polymorphism per gene with the strongest risk association in the Mayo Clinic sample was genotyped in 4,470 breast cancer cases and 4,560 controls from East Anglia, England (Studies of Epidemiology and Risk Factors in Cancer Heredity (SEARCH)). RESULTS: In the Mayo Clinic sample, six polymorphisms were associated with breast cancer risk (P trend <or= 0.05). The association with LUM rs2268578, evaluated further in SEARCH, was positive, although the odds ratios (OR) were weaker and not statistically significant. ORs were 1.4 (95% confidence interval [CI], 1.1 to 1.8) for heterozygotes and 2.2 (95% CI, 1.1 to 4.3; P2 df = 0.002) for homozygotes in the Mayo Clinic sample, and were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.4 (95% CI, 1.0 to 2.1; P2 df = 0.13) for homozygotes in the SEARCH sample. In combined analyses, the ORs were 1.1 (95% CI, 1.0 to 1.2) for heterozygotes and 1.6 (95% CI, 1.2 to 2.3; P2 df = 0.005) for homozygotes. Positive associations for this polymorphism were observed for estrogen receptor-positive tumors in both the Mayo Clinic sample (OR for heterozygotes = 1.5, 1.1 to 1.9 and OR for homozygotes = 2.5, 1.2 to 5.3;P2 df = 0.001) and the SEARCH sample (OR for heterozygotes = 1.0, 0.9 to 1.1 and OR for homozygotes = 1.6, 1.0 to 2.5; P2 df = 0.10). In combined analyses, the ORs were 1.1 (95% CI, 0.9 to 1.2) for heterozygotes and 1.9 (95% CI, 1.3 to 2.8; P2 df = 0.001) for homozygotes. CONCLUSIONS: Although LUM rs2268578 was associated with breast cancer in the Mayo Clinic study, particularly estrogen receptor-positive breast cancer, weaker and modest associations were observed in the SEARCH sample. These modest associations will require larger samples to adequately assess the importance of this polymorphism in breast cancer

Die Weltwirtschaft im Wandel: Symposium 1975

Seit einigen Jahren verstärkt sich der Eindruck, daß die Weltwirtschaft in einem raschen Wandel begriffen ist. Die Entwicklungsländer fordern eine neue Weltwirtschaftsordnung. Auf die weltweite Hochkonjunktur ist eine scharfe und recht lange anhaltende Rezession gefolgt; aber noch immer dominieren inflationäre Tendenzen. Den Konjunktureinbruch überlagert hat die Vervielfachung des Ölpreises Ende 1973. Sie wurde von vielen Beobachtern als Beginn einer Phase mit zunehmendem Rohstoffmangel und nie gekannten Ungleichgewichten in den Zahlungsbilanzen gedeutet. Von den vielfach geäußerten Befürchtungen haben sich manche als übertrieben erwiesen; denn viele Schwierigkeiten konnte der Markt viel besser als erwartet und ziemlich geräuschlos bewältigen. Gleichwohl erscheint es geraten, die alten und die neuen Probleme der Weltwirtschaft ständig zu beobachten. Vom 23. -27. Juni, traf sich in Kiel eine Gruppe unabhängiger Ökonomen aus Japan, Nordamerika und der Europäischen Gemeinschaft in der Absicht, die Situation der Weltwirtschaft zu analysieren und Vorschläge für wirtschaftspolitische Maßnahmen auf nationaler und internationaler Ebene auszuarbeiten. Das Institut für Weltwirtschaft war Gastgeber. Das Kieler Symposium ist ein Glied in einer Reihe trilateraler Konferenzen über weltwirtschaftliche Fragen, die von der Brookings Institution in Washington, dem Japan Economic Research Center in Tokio und dem Institut für Weltwirtschaft gemeinsam veranstaltet werden. Die Ergebnisse werden jeweils in englischer, japanischer und deutscher Sprache veröffentlicht; frühere Berichte in der deutschen Fassung sind als Kieler Diskussionsbeiträge Nr. 31 "Welthandel und Strukturanpassung in den Industrieländern" und Nr. 36 "Weltrohstoffversorgung: Konflikt oder Kooperation?" erschienen. --

Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer

The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n=case 192, controls 96)], breast cancer patients [ABC (n=case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2–5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI