Serum C18:1-Cer as a Potential Biomarker for Early Detection of Gestational Diabetes

We hypothesized that sphingolipids may be early biomarkers of gestational diabetes mellitus (GDM). Here, 520 women with normal fasting plasma glucose levels were recruited in the first trimester and tested with a 75 g oral glucose tolerance test in the 24th–28th week of pregnancy. Serum sphingolipids concentrations were measured in the first and the second trimester by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS) in 53 patients who were diagnosed with GDM, as well as 82 pregnant women with normal glucose tolerance (NGT) and 32 non-pregnant women. In the first trimester, pregnant women showed higher concentrations of C16:0, C18:1, C22:0, C24:1, and C24:0-Cer and lower levels of sphinganine (SPA) and sphingosine-1-phosphate (S1P) compared to non-pregnant women. During pregnancy, we observed significant changes in C16:0, C18:0, C18:1, and C24:1-Cer levels in the GDM group and C18:1 and C24:0-Cer in NGT. The GDM (pre-conversion) and NGT groups in the first trimester differed solely in the levels of C18:1-Cer (AUC = 0.702 p = 0.008), also considering glycemia. Thus, C18:1-Cer revealed its potential as a GDM biomarker. Sphingolipids are known to be a modulator of insulin resistance, and our results indicate that ceramide measurements in early pregnancy may help with GDM screening.

A Randomized Controlled Clinical Trial of Lifestyle Intervention and Pioglitazone for Normalization of Glucose Status in Chinese with Prediabetes

Aims. Prediabetes has been proved as an important risk factor of both diabetes and cardiovascular disease (CVD). Previous studies have shown that both lifestyle intervention and pioglitazone may delay the development of diabetes in patients with prediabetes. However, no study has ever explored whether these interventions could revert prediabetes to normal glycemic status as the primary outcome. Interventions that may revert prediabetes back to normal glucose status would be of great clinical importance. Materials and Methods. We conducted a randomized, multicenter, 2 × 2 factorial designed study to examine whether intensive lifestyle intervention and/or pioglitazone could revert prediabetes to normal glucose tolerance. The participants were followed up for three years unless they reverted to normal glucose state or developed diabetes at the annual oral glucose tolerance test (OGTT). Reversion to normal glucose tolerance was confirmed on the basis of the results of OGTT. Results. In our study, 1945 eligible patients were ultimately randomized into four groups. In this three-year follow-up study, overall, 60.0%, 50.3%, 56.6% and 65.1% reverted back to normoglycemic state over 3 years of follow-up in the conventional lifestyle intervention plus placebo, intensive lifestyle intervention plus placebo, conventional lifestyle intervention plus pioglitazone, and intensive lifestyle intervention plus pioglitazone groups, respectively. Compared to the conventional lifestyle intervention plus placebo group, all the other three groups did not show any significant benefit in terms of reverting back to normoglycemic state. Conclusion. In our study, for patients with prediabetes, neither intensive lifestyle intervention nor pioglitazone had led to a higher reversion rate to normal glucose state. Trail registration.http://www.chictr.org.cn: ChiCTR-PRC-06000005.

Vitamin D Status in Prediabetes and its Different Categories

Objectives: Data regarding vitamin D level and status among categories of prediabetes are scarce in the literature. This study is aimed to determine the level and status of vitamin D among adults with prediabetes and its different categories. Materials and methods: This crosssectional study was carried out in 111 newly detected adults with prediabetes according to American Diabetes Association 2018 criteria and 74 matched healthy control (normal glucose tolerance). People with prediabetes were categorized into impaired glucose tolerance, impaired fasting glucose and their combination group. Participants were recruited consecutively from the Department of Endocrinology, BSMMU to measure serum 25 hydroxyvitamin D by high performance liquid chromatography and serum intact parathormone, calcium, albumin and phosphate by chemiluminescent enzyme-labeled immunometric assay. Results: Vitamin D level and status were not significantly different between people with prediabetes & control and also in different categories of prediabetes. Severe vitamin D deficiency was significantly higher in people with prediabetes (27.5% vs 10%, p= 0.05). There were no associations between different blood glucose levels with vitamin D among adults with prediabetes. Conclusions:Vitamin D was not associated with prediabetes or its categories. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 120-128

Do Pregnancy Outcomes of Women With False-Positive Early Gestational Diabetes Mellitus Differ From Those of Women With Normal Glucose Tolerance?

Background: To investigate whether false-positive early gestational diabetes mellitus (GDM) women can be managed similarly as normal glucose tolerance (NGT) women.Methods: This retrospective study was conducted at a tertiary care center in Japan. Pregnancy and neonate outcomes of 117 singleton pregnancies with false-positive early GDM and 1774 singleton pregnancies with NGT who delivered after 22 weeks of gestation were compared. GDM was diagnosed according to the IADPSG criteria (patients having one or more of the following: fasting plasma glucose ≥ 92 mg/dL and a 75 g oral glucose tolerance test (OGTT) value ≥180 mg/dL at 1 h, or ≥153 mg/dL at 2 h). Pregnant women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria on the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation.Results: Maternal age, pre-pregnancy BMI, and gestational weight gain were significantly higher in the false-positive GDM group than the NGT group. No significant differences were found in pregnancy outcomes, including gestational age, birth weight, large for gestational age rate, and cesarean delivery rate. Except for neonatal hypoglycemia rate, no significant differences were found in neonatal outcomes.Conclusions: There were no clinically significant differences between early GDM false-positive women exhibiting GDM patterns only during early pregnancy and NGT women. False-positive early GDM women can be managed similarly as NGT women, suggesting that WHO diagnostic guidelines, applying the IADPSG criteria during early pregnancy, need revision.

Liraglutide Inhibits Osteoclastogenesis and Improves Bone Loss by Downregulating Trem2 in Female Type 1 Diabetic Mice: Findings From Transcriptomics

BackgroundThe mechanisms of bone fragility in type 1 diabetes (T1D) are not fully understood. Whether glucagon-like peptide-1 receptor (GLP-1R) agonists could improve bone quality in T1D context also remains elusive.AimsWe aimed to explore the possible mechanisms of bone loss in T1D and clarify whether liraglutide has effects on bone quality of T1D mice using transcriptomics.MethodsFemale streptozotocin-induced diabetic C57BL/6J mice were randomly divided into four groups and received the following treatments daily for 8 weeks: saline as controls, insulin, liraglutide, and liraglutide combined with insulin. These groups were also compared with non-STZ-treated normal glucose tolerance (NGT) group. Trunk blood and bone tissues were collected for analysis. Three tibia from each of the NGT, saline-treated, and liraglutide-treated groups were randomly selected for transcriptomics.ResultsCompared with NGT mice, saline-treated T1D mice manifested markedly hyperglycemia and weight loss, and micro-CT revealed significantly lower bone mineral density (BMD) and deficient microarchitectures in tibias. Eight weeks of treatment with liraglutide alone or combined with insulin rescued the decreased BMD and partly corrected the compromised trabecular microarchitectures. Transcriptomics analysis showed there were 789 differentially expressed genes mainly mapped to osteoclastogenesis and inflammation pathways. The RT-qPCR verified that the gene expression of Trem2, Nfatc1, Trap, and Ctsk were significantly increased in the tibia of T1D compared with those in the NGT group. Liraglutide treatment alone or combined with insulin could effectively suppress osteoclastogenesis by downregulating the gene expression of Trem2, Nfatc1, Ctsk, and Trap.ConclusionsTaken together, increased osteoclastogenesis with upregulated expression of Trem2 played an important role in bone loss of T1D mice. Liraglutide provided protective effects on bone loss in T1D mice by suppressing osteoclastogenesis.

Reduced Lung Function and Progression to Prediabetes: A Prospective Study

Objective: Prediabetes is a state that people have blood glucose levels higher than normal but still not in diabetes range. There is a close relationship between impaired lung function and diabetes mellitus (DM). Reduced lung function can be present before the clinical evidence of diabetes or insulin resistance. Materials and Methods: The total number of subjects in this longitudinal study was 503 and compared with apparently healthy Kashmiri adults. All the subjects, at the time of their first visit, underwent Fasting Plasma Glucose (FPG) estimation, 2- hour oral glucose tolerance test (OGTT) and spirometry (FVC, FEV1 & FEV1/FVC). Those subjects who had normal glucose tolerance (NGT) were retested for glycemic status and spirometric values after a follow-up period of 2-18 (mean=10) months. Results: Out of total 503 subjects on follow up 483 (96%) had NGT and 20 (4%) had prediabetes. Percent predicted forced vital capacity (FVC) and % predicted forced expiratory volume in 1st second (FEV1) were significantly lower (P-value< 0.001) while as % predicted FEV1/FVC was significantly higher (P-value< 0.001) in prediabetes as compared to NGT group. Conclusion: Results of our study point out a predominantly restrictive pattern of lung dysfunction in the prediabetes group as compared to the NGT group.

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.

Evidence That Hypothalamic Gliosis Is Related to Impaired Glucose Homeostasis in Adults With Obesity

Objective: Preclinical research implicates hypothalamic glial cell responses in the pathogenesis of obesity and type 2 diabetes. The current study sought to translate such findings into humans by testing if radiologic markers of gliosis in the mediobasal hypothalamus (MBH) were greater in persons with obesity and impaired glucose homeostasis or type 2 diabetes. <p>Research Design and Methods: Using cross-sectional and prospective cohort study designs, we applied a validated, quantitative magnetic resonance imaging (MRI) approach to assess gliosis in 67 adults with obesity and normal glucose tolerance, impaired glucose tolerance, or type 2 diabetes. Assessments of glucose homeostasis were conducted via oral glucose tolerance tests (OGTT) and β-cell modeling. </p> <p> Results: We found significantly greater T2 relaxation times (a marker of gliosis by MRI), that were independent of adiposity, in the impaired glucose tolerance and type 2 diabetes groups as compared to the normal glucose tolerance group. Findings were present in the MBH, but not control regions. Moreover, positive linear associations were present in the MBH but not control regions between T2 relaxation time and glucose area under the curve during an OGTT, fasting glucose concentrations, hemoglobin A1c, and visceral adipose tissue mass, whereas negative linear relationships were present in the MBH for markers of insulin sensitivity and β-cell function. In a prospective cohort study, greater MBH T2 relaxation times predicted declining insulin sensitivity over one year. </p> Conclusions: Findings support a role for hypothalamic gliosis in the progression of insulin resistance in obesity and, thus, type 2 diabetes pathogenesis in humans.