Daily Rhythms of Plasma Melatonin, but Not Plasma Leptin or Leptin mRNA, Vary between Lean, Obese and Type 2 Diabetic Men

Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM). We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45–65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO), nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01) and lean controls (p<0.05). Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001) effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual’s 24-hour mean, plasma leptin showed significant (p<0.001) diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05) of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither obesity nor T2DM changed 24-hour rhythms of plasma leptin relative to cycle mean, or expression of subcutaneous adipose leptin gene expression, compared with lean subjects

Anerkennung informell erworbener Kompetenzen aus bildungspolitischer und wirtschaftswissenschaftlicher Perspektive

Ausgehend von einer Skizzierung bildungspolitischer Entwicklungen zur Anerkennung informellen Lernens werden als in der Bildungspraxis wirksam gewordene Ansätze die Europass-Initiative und das ProfilPASS-System vorgestellt. Im zweiten Abschnitt des Beitrages werden als theoretische Bezugspunkte zunächst die Neue Institutionenökonomik und die Bildungsproduktionsfunktion entfaltet, auf die beiden Ansätze bezogen und auf dieser Grundlage weiterführende Überlegungen angestellt. (DIPF/Orig.

Spine surgery in pregnant women: a multicenter case series and proposition of treatment algorithm

Purpose!#!Spinal diseases requiring urgent surgical treatment are rare during pregnancy. Evidence is sparse and data are only available in the form of case reports. Our aim is to provide a comprehensive guide for spinal surgery on pregnant patients and highlight diagnostic and therapeutic aspects.!##!Methods!#!The study included a cohort of consecutive pregnant patients who underwent spinal surgery at five high-volume neurosurgical centers between 2010 and 2017. Perioperative and perinatal clinical data were derived from medical records.!##!Results!#!Twenty-four pregnant patients were included. Three underwent a preoperative cesarean section. Twenty-one patients underwent surgery during pregnancy. Median maternal age was 33 years, and median gestational age was 13 completed weeks. Indications were: lumbar disk prolapse (n = 14; including cauda equina, severe motor deficits or acute pain), unstable spine injuries (n = 4); intramedullary tumor with paraparesis (n = 1), infection (n = 1) and Schwann cell nerve root tumor presenting with high-grade paresis (n = 1). Two patients suffered transient gestational diabetes and 1 patient presented with vaginal bleeding without any signs of fetal complications. No miscarriages, stillbirths, or severe obstetric complications occurred until delivery. All patients improved neurologically after the surgery.!##!Conclusion!#!Spinal surgical procedures during pregnancy seem to be safe. The indication for surgery has to be very strict and surgical procedures during pregnancy should be reserved for emergency cases. For pregnant patients, the surgical strategy should be individually tailored to the mother and the fetus

Diurnal rhythms of plasma leptin concentrations.

<p>(a) Analysis of absolute concentration revealed a significant effect of group (<i>p</i><0.001; 2-way repeated measures ANOVA) but not of time or time x group interaction. *<i>p</i><0.05 lean vs type 2 diabetic subjects. (b–c) Following normalisation of each individual’s raw data to their own mean concentration, the group values were calculated and fitted with a cosinor curve. Normalised data are expressed relative to (b) external time of day and (c) endogenous circadian time, estimated using DLMO where 360°  =  time of DLMO. The DLMO of two participants in the type 2 diabetic participant group could not be calculated due to the absence of a peak in the melatonin profile; their data were thus excluded. Statistical analysis showed a significant effect of time (<i>p</i><0.001; 2-way repeated measures ANOVA) but not for group or interaction in both (b) and (c). (a–b) The light-dark conditions are indicated by the bars below the x-axes. In all panels, diamonds, solid red line  =  lean subjects (n = 8); square, dashed blue line  =  obese non-diabetic subjects (n = 10); triangle, dotted black line  =  type 2 diabetic subjects (n = 7).</p

Differences in amplitude, but not onset time, of nocturnal plasma melatonin concentration.

<p>(a) Data in the top panel represent mean ± SEM of plasma melatonin concentrations over 25 hours. Diamonds, solid red line  =  lean subjects (n = 8); squares, dashed blue line  =  obese non-diabetic subjects (n = 10); triangles, dotted black lines  =  type 2 diabetic subjects (n = 7). The light-dark conditions are indicated by the bar below the x-axis. There was a significant (<i>p</i>0.001; 2-way repeated measures ANOVA) effect of time, group and time x group interaction. Nocturnal melatonin concentrations were significantly higher in the obese non-diabetic group (⁺<i>p</i><0.05, vs lean, **<i>p</i><0.01 vs type 2 diabetic subjects). (b) Data in the bottom panel represent mean ± SEM of the dim light melatonin onset (DLMO) in each group. There was no significant (<i>p</i>>0.05, 1-way ANOVA) difference between the group averages. Lean  =  lean healthy participant group; ow  =  obese non-diabetic group; T2DM  =  type 2 diabetic group.</p

Expression of leptin mRNA in white adipose biopsies.

<p>(a) Data represent mean ± SEM of leptin mRNA in 6-hourly serial biopsies. There was a significant effect of group (<i>p</i><0.05; 2-way repeated measures ANOVA), but not of time or time x group interaction. There were no significant (<i>p</i>>0.05; Bonferroni post-hoc test) pair wise differences in leptin mRNA expression between the subject groups. The light-dark conditions are indicated by the bars below the x-axis. Diamonds, solid red line  =  lean subjects (n = 8); squares, dashed blue line  =  obese non-diabetic subjects (n = 10); triangles, dotted black line  =  type 2 diabetic group (n = 7). The average leptin mRNA expression for each subject was significantly (<i>p</i><0.05) correlated with both (b) average plasma leptin concentrations and (c) subjects’ BMI. (d) The average plasma leptin concentration for each subject was significantly (<i>p</i><0.001) correlated with subjects’ BMI.</p

Acrophase (peak time) and amplitude of the leptin rhythms determined by cosinor analysis.

<p>A cosine wave was fitted to each individual leptin profile. There was no significant (<i>p</i>>0.05; 1-way ANOVA) effect of group on either the acrophase (peak time) or amplitude of the rhythms. The acrophase of the leptin rhythm was also corrected to the dim light melatonin onset (DLMO).</p

Pre-screen participant data.

*<p><i>P</i><0.05 compared to lean participants; ⁺<i>P</i><0.05 compared to obese non-diabetic participants (1-way ANOVA with Bonferroni post-hoc test).</p