Goji Berry (Lycium barbarum) Supplementation during Pregnancy Influences Insulin Sensitivity in Rabbit Does but Not in Their Offspring

This study investigated the effects of Goji berry (Lycium barbarum) dietary supplementation during pregnancy on insulin sensitivity of rabbit does and their offspring. Starting from two months before the artificial insemination, 75 New Zealand White does were fed only commercial standard diet (C) or supplemented with 1% (G1) and 3% (G3) of Goji berries. Their offspring received a standard diet but kept the nomenclature of the mother’s group. Fasting and intravenous glucose tolerance test-derived indices were estimated at 21 days of pregnancy on rabbit does and at 90 days of age on the offspring. No difference was found in the fasting indices, while the diet modulated the response to glucose load of rabbit does. In particular, G3 group had the lowest glucose concentrations 5 min after the bolus administration (p < 0.05) and, as a result, differed in the parameters calculated during the elimination phase such as the elimination rate constant (Kel), the half-life of the exogenous glucose load (t1/2), and apparent volume of distribution (Vd; for all, p < 0.05). The high dose of Goji supplementation could thus enhance the first-phase glucose-induced insulin secretion. Findings on the offspring were inconsistent and therefore a long-term effect of Goji supplementation during pregnancy could not be demonstrated. Further study on the effect of Goji on the secretory pathway of insulin could clarify its hypoglycaemic action, while different protocols are needed to investigate its potential effects on foetal programming.

The Beta-Cell Function and Glucose Profile of Newly Diagnosed Acromegalic Patients with Normal Glucose Tolerance

Objectives. Untreated acromegaly is a nature model for unveiling the diabetogenic effects of GH. CGMS can uncover more glucose profile of acromegaly. This study aimed to evaluate the insulin resistance (IR), β-cell function, and glycemic spectrum of patients with newly diagnosed acromegaly with normal glucose tolerance (NGT). Methods. This study was conducted in Huashan Hospital from January 2015 to February 2019. Eight newly diagnosed acromegalic patients without history of diabetes and eight age- and gender-matched healthy subjects were enrolled. All participants underwent oral glucose tolerance test (OGTT) and 72 h continuous glucose monitoring (CGM). Parameters on β-cell function and IR were calculated. Mean blood glucose (MBG) in 24 hours was adopted for the evaluation of the glycemic level, and standard deviation of blood glucose (SDBG) and mean amplitude of glycemic excursion (MAGE) were used for glucose fluctuation. Results. HbA1c in the acromegaly group was significantly higher than in the control. During OGTT, glucose peaked at 60 min in acromegaly and at 30 min in controls. After glucose load, the acromegaly group had significantly higher insulin levels than controls, especially in 120 min and 180 min. Both insulin sensitivity index and disposal index after glucose load of acromegaly were significantly lower than those of controls. Moreover, acromegalic subjects had significantly higher MBG than controls. Conclusions. The newly diagnosed acromegalic patients with NGT were characterized by IR and impaired β-cell function after glucose load. CGM showed that MBG of NGT acromegaly patients was higher than that of normal people.

Oral Glucose Load and Human Cutaneous Microcirculation: An Insight into Flowmotion Assessed by Wavelet Transform

Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.

Maternal Metabolites Associated with Gestational Diabetes Mellitus and a Postpartum Disorder of Glucose Metabolism

Objective To identify circulating metabolites present at ~28 weeks’ gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10-14 years later. Methods Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hr serum samples following a 75g glucose load at ∼28 weeks’ gestation from 2,290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Postpartum metabolic traits included fasting and 2-hr plasma glucose following a 75g glucose load, insulin resistance estimated by homeostasis model assessment, and disorders of glucose metabolism (prediabetes and type 2 diabetes) during the HAPO Follow-Up Study. Results Per-metabolite analyses identified numerous metabolites, ranging from amino acids and carbohydrates to fatty acids and lipids, before and 1-hr after a glucose load that were associated with GDM as well as development of a disorder of glucose metabolism and metabolic traits 10-14 years postpartum. A core group of fasting and 1-hr metabolites mediated, in part, the relationship between GDM and postpartum disorders of glucose metabolism, with the fasting and 1-hr metabolites accounting for 15.7% (7.1%-30.8%) and 35.4% (14.3%-101.0%) of the total effect size, respectively. For prediction of a postpartum disorder of glucose metabolism, addition of circulating fasting or 1-hr metabolites at ~28 weeks’ gestation showed little improvement in prediction performance compared to clinical factors alone. Conclusions The results demonstrate association of multiple metabolites with GDM and postpartum metabolic traits and begin to define the underlying pathophysiology of the transition from GDM to a postpartum disorder of glucose metabolism.

Clinical and hormonal findings in patients presenting with high IGF-1 and growth hormone suppression after oral glucose load - a retrospective cohort study

Objective: high IGF-1 and unsuppressed GH levels after glucose load confirm the diagnosis of acromegaly. Management of patients with conflicting results could be challenging. Our aim was to evaluate the clinical and hormonal evolution over a long follow-up in patients with high IGF-1 but normal GH nadir (GHn<0.4 μg/L according to the latest guidelines). Design: retrospective cohort study. Methods: we enrolled 53 patients presenting high IGF-1 and GHn<0.4 μg/L, assessed because of clinical suspicion of acromegaly or in other endocrinological contexts (e.g., pituitary incidentaloma). Clinical and hormonal data collected at the first and last visit were analyzed. Results: at the first evaluation, the mean age was 54.1±15.4 years, 34/53 were females, median IGF-1 and GHn were +3.1 SDS and 0.06 μg/L, respectively. In the whole group, over a median time of 6 years, IGF-1 and GHn levels did not significantly change (IGF-1 mean of differences -0.58, p=0.15; GHn +0.03, p=0.29). In patients with clinical features of acromegaly, the prevalence of acromegalic comorbidities was higher than in the others (median of 3 vs 1 comorbidities per patient, p=0.005), especially malignancies (36% vs 6%, p=0.03), and the clinical worsening overtime was more pronounced (4 vs 1 comorbidities at the last visit). Conclusions: in patients presenting high IGF-1 but GHn<0.4 μg/L, a hormonal progression is improbable, likely excluding classical acromegaly on its early stage. However, despite persistently low GH nadir values, patients with acromegalic features present more acromegalic comorbidities whose rate increases over time. Close clinical surveillance in this group is advised.

Characteristics and treatment responsiveness of patients with acromegaly and a paradoxical GH increase to oral glucose load

Objectives: We aimed to investigate the clinical, biochemical, histological and radiological characteristics as well as the response to somatostatin analogs (SSA) in a large cohort of acromegaly patients with a paradoxical GH response (PR) to oral glucose tolerance test (OGTT). Design: retrospective study. Methods: Of 110 patients with acromegaly included in our study, 30 (PR+; 27%) had a paradoxical GH increase of more than 25% relative to basal GH levels during OGTT. Results : At diagnosis, PR+ patients were older than PR- patients (52 ± 16 vs 44 ± 14 years, p<0.05) and had smaller pituitary tumours (40% microadenomas vs 19%, p<0.05), which were less often invasive (17 vs 35%, p<0.05), overall more secreting (IGF-1/tumoural surface: 2.35 ULN/cm² [0.28-9.06] vs 1.08 [0.17- 7.87], p=0.011), and more often hypointense on T2-weighted MRI (92 vs 48%, p=0.001). While the rate of remission after surgery was similar in the two groups (69%), a better response to SSA treatment was observed in PR+ patients, either before (IGF-1 reduction of > 50% after 3-6 months in 77 vs 49%, p=0.023) or after surgery (normalization of IGF-1 in 100 vs 44%, p=0.011). Conclusions: Our study demonstrates that in acromegaly, a paradoxical GH increase during OGTT is associated with particular features of somatotroph adenomas and with a better prognosis in terms of response to somatostatin analogs.