Obesity is associated with local T-cell abnormalities in adipose tissue. Systemic obesity-related abnormalities in the peripheral blood T-cell compartment are not well defined. In this study, we investigated the peripheral blood T-cell compartment of morbidly obese and lean subjects. We determined all major T-cell subpopulations via six-color flow cytometry, including CD8+ and CD4+ T cells, CD4+ T-helper (Th) subpopulations, and natural CD4+CD25+FoxP3+ T-regulatory (Treg) cells. Moreover, molecular analyses to assess thymic output, T-cell proliferation (T-cell receptor excision circle analysis), and T-cell receptor-β (TCRB) repertoire (GeneScan analysis) were performed. In addition, we determined plasma levels of proinflammatory cytokines and cytokines associated with Th subpopulations and T-cell proliferation. Morbidly obese subjects had a selective increase in peripheral blood CD4+ naive, memory, natural CD4+CD25+FoxP3+ Treg, and Th2 T cells, whereas CD8+ T cells were normal. CD4+ and CD8+ T-cell proliferation was increased, whereas the TCRB repertoire was not significantly altered. Plasma levels of cytokines CCL5 and IL-7 were elevated. CD4+ T-cell numbers correlated positively with fasting insulin levels. The peripheral blood T-cell compartment of morbidly obese subjects is characterized by increased homeostatic T-cell proliferation to which cytokines IL-7 and CCL5, among others, might contribute. This is associated with increased CD4+ T cells, with skewing toward a Treg- and Th2-dominated phenotype, suggesting a more anti-inflammatory set point.

In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Gauna C, Kiewiet RM, Janssen JA, van de Zande B, Delhanty PJ, Ghigo E, Hofland LJ, Themmen AP, van der Lely AJ. Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions. Am J Physiol Endocrinol Metab 293: E697-E704, 2007. First published June 19, 2007; doi:10.1152/ajpendo.00219.2007.-Acylated and unacylated ghrelin (AG and UAG) are gut hormones that exert pleiotropic actions, including regulation of insulin secretion and glucose metabolism. In this study, we investigated whether AG and UAG differentially regulate portal and systemic insulin levels after a glucose load. We studied the effects of the administration of AG (30 nmol/kg), UAG (3 and 30 nmol/kg), the ghrelin receptor antagonist [D-Lys 3 ]GHRP-6 (1 mol/kg), or various combinations of these compounds on portal and systemic levels of glucose and insulin after an intravenous glucose tolerance test (IVGTT, D-glucose 1 g/kg) in anesthetized fasted Wistar rats. UAG administration potently and dose-dependently enhanced the rise of insulin concentration induced by IVGTT in the portal and, to a lesser extent, the systemic circulation. This UAG-induced effect was completely blocked by the coadministration of exogenous AG at equimolar concentrations. Similarly to UAG, [D-Lys 3 ]GHRP-6, alone or in combination with AG and UAG, strongly enhanced the portal insulin response to IVGTT, whereas exogenous AG alone did not exert any further effect. Our data demonstrate that, in glucose-stimulated conditions, exogenous UAG acts as a potent insulin secretagogue, whereas endogenous AG exerts a maximal tonic inhibition on glucose-induced insulin release. acylated ghrelin; insulin secretion; portal vein; rat GHRELIN IS A GUT HORMONE predominantly produced in the stomach and, to a lesser extent, in other regions of the gastrointestinal tract (9,21,22). Ghrelin circulates in the bloodstream in two different forms: acylated (or n-octanoylated) and unacylated (or des-octanoylated or des-acylated) (21). Acylated ghrelin (AG) has a unique feature: a posttranslational esterification of a fatty (n-octanoic or, to a lesser extent, n-decanoic) acid on serine residue at position 3 (21). This acylation is considered necessary for AG's actions via the growth hormone secretagogue receptor type 1a (GHS-R1a), also called ghrelin receptor (GRLN-R) (7, 21). However, normally AG accounts for less than 10% of the total ghrelin in the circulation. The majority of circulating ghrelin is unacylated (UAG), which binds with high affinity to a receptor, different from GHS-R1a and yet unknown (21,25).Both AG and UAG have pleiotropic activities, including regulation of insulin secretion and glucose metabolism. It has been shown that endogenous AG and UAG are also produced in the endocrine pancreas, which also expresses the GHS-R1a (6,8,13,26,27). It has been found that endogenous AG in the pancreas inhibits the glucose-induced insulin release via the GHS-R1a (8), as demonstrated by the marked increase of insulin response to glucose after blockade of endogenous AG (i.e., v...

Objective: To investigate the effects of unacylated ghrelin (UAG) and co-administration of acylated ghrelin (AG) and UAG in morbid obesity, a condition characterized by insulin resistance and low GH levels. Design and method: Eight morbidly obese non-diabetic subjects were treated with either UAG 200 mg, UAG 100 mg in combination with AG 100 mg (Comb) or placebo in three episodes of 4 consecutive days in a double-blind randomized crossover design. Study medication was administered as daily single i.v. bolus injections at 0900 h after an overnight fast. At 1000 h, a standardized meal was served. Glucose, insulin, GH, free fatty acids (FFA) and ghrelin were measured up to 4 h after administration. Results: Insulin concentrations significantly decreased after acute administration of Comb only, reaching a minimum at 20 min: 58.2G3.9% of baseline versus 88.7G7.2 and 92.7G2.6% after administration of placebo and UAG respectively (P!0.01). After 1 h, insulin concentration had returned to baseline. Glucose concentrations did not change after Comb. However, UAG administration alone did not change glucose, insulin, FFA or GH levels. Conclusion: Co-administration of AG and UAG as a single i.v. bolus injection causes a significant decrease in insulin concentration in non-diabetic subjects suffering from morbid obesity. Since glucose concentration did not change in the first hour after Comb administration, our data suggest a strong improvement in insulin sensitivity. These findings warrant studies in which UAG with or without AG is administered for a longer period of time. Administration of a single bolus injection of UAG did not influence glucose and insulin metabolism.

Our patient was diagnosed with osteoporosis pseudoglioma syndrome/familial exudative vitreoretinopathy. Potential underlying genetic causes should be considered in pregnancy-associated osteoporosis with implications for patients and relatives. More studies regarding osteoporosis treatment preceding conception are desirable.