Maternal Pre-Pregnancy Obesity Combined With Abnormal Glucose Metabolism Further Increases Adverse Pregnancy Outcomes in Chinese Pregnant Women

AimsOur aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes.MethodsA total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups.ResultsCompared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286–7.156]; 1.993 [1.171–3.393]; 8.495 [4.982–14.485]), preeclampsia (2.649 [1.224–5.735]; 2.129 [1.128–4.017]; 4.643 [2.217–9.727]), cesarean delivery (1.589 [1.212–2.083]; 1.328 [1.095–1.611]; 2.627 [1.908–3.617]), preterm delivery (1.899 [1.205–2.993]; 1.358 [0.937–1.968]; 2.301 [1.423–3.720]), macrosomia (2.449 [1.517–3.954]; 1.966 [1.356–2.851]; 4.576 [2.895–7.233]), and total adverse maternal outcomes (1.762 [1.331–2.332]; 1.365 [1.122–1.659]; 3.228 [2.272–4.587]) and neonatal outcomes (1.951 [1.361–2.798]; 1.547 [1.170–2.046]; 3.557 [2.471–5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone.ConclusionsMaternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice

Dietary sterols are catabolized into various substances in the intestinal tract. Dietary 3-oxo derivatives of cholesterol and plant sterols (e.g., cholest-4-en-3-one and campest-5-en-3-one) have been shown to have anti-obesity effects. In this study, we tested whether feeding cholest-5-en-3-one (5-cholestenone), a cholesterol metabolite, to db/db mice protects them from obesity-associated metabolic disorders. In db/db mice, dietary 5-cholestenone significantly alleviated hepatomegaly and elevated serum triglyceride levels; however, the effect was not sufficient to improve hepatic steatosis and obesity. On the other hand, hyperglycemia and severe hyperinsulinemia in control db/db mice were markedly attenuated in 5-cholestenone-fed db/db mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNFα), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in db/db mice. Additionally, 5-cholestenone showed an inhibitory effect on TNFα-induced nuclear factor kappa B (NFκB) activation in the NFκB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed db/db mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway.

Abnormal Glucose Metabolism Leads To Severe COVID-19 Due To Hyperinflammation: A Cross-Sectional Study

Background: We aimed to describe the clinical features of novel coronavirus disease 2019 (COVID-19) patients with or without diabetes, focusing on the effect of abnormal HbA1c levels on inflammatory reactions and disease severity.Methods: A total of 190 patients with COVID-19 were included in this cross-sectional study. Clinical and laboratory characteristics were collected and compared among moderate, severe, and critical cases, as well as among diabetes, prediabetes and nondiabetes cases. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic ability of HbA1c for disease severity. Logistic regression was used to explore the relationship between HbA1c levels and worse prognosis of COVID-19.Results: HbA1c levels at admission were significantly different in patients with moderate, severe, and critical diseases (P<0.001). The area under the curve (AUC) of HbA1c levels to distinguish between moderate and severe-critical diseases was 0.938 (95% CI 0.906–0.970). After adjustment for confounders, the results showed that the increasing odds of in-hospital deaths were associated with HbA1c levels >6.0% (42 mmol/mol) (aOR 2.971 [95% CI 1.002, 8.804], P=0.049), and the increasing odds of severe or critical COVID-19 were associated with HbA1c levels ≥5.7% (39 mmol/mol) (aOR 29.588 [95% CI 8.285, 105.457], P<0.001). In addition, HbA1c levels strongly correlated with inflammatory markers and cytokines.Conclusions: Abnormal glucose metabolism can cause a hyperinflammatory state of COVID-19, which manifests as severe disease.

Scavenging ROS Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe Cells

Dysregulated glucose metabolism in the brain is considered to be the underlying cause of Alzheimer's disease (AD). Abnormal glucose metabolism in AD is associated with decreased glucose transporter 1 (GLUT1) and GLUT3 in the brain, but the underlying mechanisms remains unclear. Here, we reported that GLUT1 expression was decreased in N2a/APP695swe cells and GLUT3 expression was not significantly changed. Flow Cytometry analysis showed a significant increase of intracellular ROS content in N2a/APP695swe cells and GLUT1 expression was upregulated after treatment with the ROS scavenger N-acetyl-L-Cysteine (NAC). Cellular glucose uptake and ATP levels were reduced following decreased GLUT1 expression and increased after upregulating GLUT1. Western blot analyses showed that phosphorylation of PI3K/Akt pathway decreased in N2a/APP695swe cells. Aβ levels decreased after upregulation of GLUT1 expression and increased after downregulation of GLUT1. After NAC treatment, PI3K/Akt pathway phosphorylation levels and GLUT1 expression were upregulated, glucose uptake and ATP contents were increased, and Aβ levels were decreased. After adding PI3K/Akt pathway inhibitor LY29004, GLUT1 expression was reduced and Aβ levels were increased. Besides, the increased glucose uptake and ATP contents by the Akt activator SC79 were hindered with the GLUT1 inhibitor WZB117. Aβ levels decreased after SC79 treatment and increased after WZB117 treatment. Overall, our data suggest that ROS reduced GLUT1 expression by inhibiting PI3K/Akt pathway activity resulting in impaired glucose metabolism and scavenging ROS prevents Aβ via activation of PI3K/Akt/GLUT1 pathway in N2a/APP695swe cells.

Glycemic Status in Acromegaly Patients Receiving Depot Long-Acting Octreotide

Background: Acromegaly is an uncommon, chronic, debilitating condition characterized by hyperinsulinism, insulin resistance, diabetes and prediabetes. One possibility for managing acromegaly's questionable influence on glucose homeostasis is the somatostatin analogues. Aim: To analyze the frequency and risk factors for impaired glucose homeostasis in acromegaly patients treated with depot long-acting octreotide (octreotide LAR), as well as the relationship between risk and treatment duration. Methods: The study included 52 Iraqi adults with acromegaly receiving octreotide LAR. Demographic, anthropometric, and clinical data were collected, as well as the duration of Octreotide LAR administration. Growth hormone, IGF-1, and adenoma size were reported retrospectively from patient data. The glycemic state was assessed and classified as DM, prediabetes, or normal. Results: The prevalence of DM was 39% and prediabetes was 40%, with the exception of being male, which was substantially related with prediabetes. DM and octreotide LAR use had a non-significant correlation. However, octreotide use altered 13% of patients from normal glycemic to prediabetes, with no correlation to treatment duration. Other than hypertension and a family history of diabetes, no other variables were found to be significant. Conclusion: Acromegaly patients have abnormal glucose metabolism, which is associated with prediabetes owing to octreotide LAR medication. Hypertension and family history of diabetes are risk factors.

PA and OA induce abnormal glucose metabolism by inhibiting KLF15 in adipocytes

Background Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Methods Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. Results KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Conclusions Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.

Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study

Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011–2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.