The Distributional Characteristics of M2 Macrophages in the Placental Chorionic Villi are Altered Among the Term Pregnant Women With Uncontrolled Type 2 Diabetes Mellitus.

Aim: No definite conclusions have been drawn regarding how prolonged exposure to hyperglycemia affects the distribution of macrophages in the placenta, especially in pregnant women with uncontrolled type 2 diabetes mellitus (T2DM). Herein, we explored the distributional characteristics of placental M2 macrophages, including hofbauer cells (HBCs) in the chorionic villi and decidual macrophages, in pregnant women with uncontrolled T2DM. Methods: Six healthy singleton pregnancies and five uncontrolled T2DM singleton pregnancies were collected. Multicolor immunofluorescence and immunohistochemistry were performed to record M1 macrophages by CD80 and CD86, the general M2 macrophages by CD163, M2a macrophages by CD163 and DG-SIGN, M2b macrophages by CD163 and CD86, and M2c macrophages by CD163 and CD206. Meanwhile, the monocyte marker of CD14 and the general macrophage marker of CD68 were also documented on placenta. Results: In the chorionic villi and decidua, the most common infiltrated macrophages was the general M2. There were only few M1 and M2b macrophages distributed in the placenta of both the healthy and uncontrolled T2DM groups. The infiltrated degree of M2c macrophages was moderate in chorionic villi and decidua. The uncontrolled T2DM and healthy pregnant women had a comparable amount of M2c macrophages infiltration in the chorionic villi (p = 0.158). Notedly, in both of the healthy and uncontrolled T2DM pregnant women, the predominant subtype of M2 macrophages in the chorionic villi was M2a, where it mainly infiltrated around vessels and syncytiotrophoblasts. The uncontrolled T2DM pregnant women had more M2a macrophage infiltration than the healthy pregnant women (p = 0.016). The M2a macrophages in the decidua of the uncontrolled T2DM group were similar to those of the normal group (p = 0.800). Meanwhile, it was in the chorionic villi but not the decidua, that the CD68+ macrophages and CD14+ M2a macrophages were also elevated in the uncontrolled T2DM group (p = 0.035 and 0.044, respectively). Conclusion: These results confirmed that the M2 macrophages exhibited increased in the chorionic villi of pregnant women with uncontrolled T2DM. The subsets of M2 macrophages in the placental decidua were similar between uncontrolled T2DM pregnant women and normal groups. It may provide a basis for exploring the functions of different subsets of macrophages in the placental chorionic villi.

Xingnaojing injection and insulin pump combined with decompression in treatment of severe craniocerebral injury with diabetes mellitus / 中华内分泌外科杂志

Objective:To investigate the clinical efficacy and adverse reactions of Xingnaojing injection combined with insulin pump in treatment of severe craniocerebral injury (STBI) complicated with diabetes mellitus.Methods:Data of 102 patients with STBI combined with diabetes mellitus admitted from Jan. 2017 to Jan. 2020 in the Surgical Intensive Care Unit of Yantaishan Hospital were prospectively analyzed. Their average age was (48.27±4.20) years. They were randomly divided into group A (34 cases, treated with simple decompression) , group B (34 cases, treated with insulin pump combined decompression) and group C (34 cases, treated with Xingnaojing injection and insulin pump combined decompression) . Fasting blood glucose (FPG) , 2 h postprandial blood glucose level (2 h PG) , interleukin 2 (IL-2) , interleukin 6 (IL-6) , serum high sensitivity C-reactive protein (hs CRP) and glasgow coma scale (GCS) was different, and the incidence of adverse reactions was recorded. SPSS 23.0 statistical software was used for data processing. The measurement data were mean±standard deviation, and t test was used; the counting data were expressed in (%) and χ 2 inspection was used. Results:After treatment, there was no significant difference in 2 h PG, FPG, IL-2, IL-6, hs CRP or GCS scores between group A and group B ( P>0.05) . After treatment, the levels of 2 h PG and FPG were (8.89±1.74) mmol/L and (7.53±1.59) mmol/L in group C, (7.30±1.62) mmol/L and (6.25±1.50) mmol/L in group A, (7.32±1.64) mmol/L and (6.29±1.56) mmol/L in group B. The levels in group C were higher than those in group A and group B ( P<0.05) . The levels of IL-2, IL-6 and hs CRP in group C were (792.74±86.58) ng/L, (8.82±1.73) ng/L and (7.95±1.44) mg/L respectively. The three indexes were (880.85±90.29) ng/L, (13.85±2.20) ng/L and (14.02±2.28) mg/L respectively in group A; (875.37±89.72) ng/L, (13.34±2.18) ng/L, and (13.37±2.26) mg/L respectively in group B. Group C was lower than group A and group B ( P<0.05) . The GCS score of group C was 11.45±2.23 (points) , and that of group A and group B were 8.09±1.52 (points) and 8.73±1.56 (points) respectively. Group C was higher than that of group A and group B ( P<0.05) . Compared with group A and group B, the incidence of adverse reactions in group C was lower, and the difference was statistically significant ( P<0.05) . Conclusion:Xingnaojing injection and insulin pump combined with decompression are of great significance in reducing adverse reactions and improving the safety of clinical treatment.

SGLT-2 Inhibitors in Type 1 Diabetes Mellitus: A Comprehensive Review of the Literature.

BACKGROUND: Sodium-Glucose Cotransporter 2 (SGTL-2) inhibitors are a new class of antidiabetics, which have been approved for the treatment of patients with Type 2 Diabetes Mellitus (T2DM). Besides their beneficial metabolic effects, they exert favourable results in cardiovascular events and risk factors along with renoprotection. However, SGLT-2 inhibitors have not been yet approved as an adjunct therapy to insulin in patients with Type 1 Diabetes Mellitus (T1DM). This review aims at presenting both clinical and experimental data that reinforce the role of SGLT-2 inhibitors as adjunctive treatment in patients with T1DM along with the main restrictions of their use, namely Diabetic Ketoacidosis (DKA). METHODS: We conducted a comprehensive research of the relevant literature regarding the off-label use of SGLT-2 inhibitors in clinical practice, presenting the major benefits and the potential risks. RESULTS: SGLT-2 inhibitors are associated with improved glycemic control, reduction in body weight, and decrease in insulin dosage, along with their beneficial cardiovascular and renal effects. However, we cannot overlook the association with increased incidence of DKA events, in the presence of well known predisposing factors. Further investigation is required, in order to establish them as adjunctive treatment in those patients. CONCLUSION: This novel class of antidiabetics seems to be a very attractive treatment option in patients with T1DM, due to their multiple beneficial effects, but the increased risk of DKA should be taken into account.

Relationship between plasma progranulin and insulin resistance in patients with type 2 diabetes mellitus and obesity / 中华内分泌代谢杂志

Objective To detect plasma progranulin (PGRN) level in subjects with newly diagnosed type 2 diabetes mellitus and to investigate the relationship of plasma PGRN level with glycolipid metabolism,inflammation,and insulin resistance.Methods Eighty patients with newly diagnosed type 2 diabetes (T2DM) and 88 subjects with normal glucose tolerance (NGT) were recruited in the study.Both of them were divided into normal weight (NW)subgroup and obesity (OB) subgroup.Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 according to the World Health Organization-Western Pacific Region diagnostic criteria(2000).Body fat parameters were measured and BMI,waist-to-hip ratio were determined.Fasting plasma PGRN and interleukin-6 (IL-6) levels were determined by ELISA,fasting plasma glucose (FPG),2 h plasma glucose after glucose loading (2hPG),HbA1C,fasting insulin (FINS),and lipids were also detected.Insulin resistance and pancreas β cell function were assessed by homeostasis model assessment (HOMA-IR,HOMA-β).Results Plasma PGRN level was significantly higher in T2DM group than that in NGT group(P＜0.01).Within groups of T2DM and NGT,plasma PGRN level in OB subgroups was higher than that in NW subgroups [(225.22 ± 34.39 vs 195.59 ± 50.47 and 183.79 ± 61.63 vs 148.69 ± 55.27) ng/ml,P＜0.05].Bivariate correlation analysis showed that plasma PGRN level was positively correlated with weight,waist circumference,BMI,systolic blood pressure,FPG,2hPG,HbA1C,triglyceride(TG),IL-6,FINS,and HOMA-IR (P＜0.05 or P＜0.01),and was negatively correlated with HOMA-β (P＜0.05).Multiple linear regression analysis showed that BMI,HbA1C,IL-6,and TG were independently related to plasma PGRN level(P＜0.05).Conclusions Plasma PGRN level was increased in patients with type 2 diabetes as well as in obesity,and was closely related with glycolipid metabolism,inflammation,and insulin resistance.

Imunoproteção de ilhotas pancreáticas microencapsuladas em biomateriais inovadores e seu potencial terapêutico no diabetes mellitus tipo 1 / Immunoprotection of pancreatic islets microencapsulated in inovative biomaterials and its therapeutic potential in type 1 Diabetes Mellitus

O transplante de ilhotas microencapsuladas constitui uma alternativa terapêutica interessante para o Diabetes Mellitus tipo 1, permitindo um melhor controle glicêmico e eliminando a necessidade de imunossupressão. Entretanto, a manutenção a longo prazo da viabilidade das células-β ainda é um desafio. No isolamento, a perda da matriz extracelular e as condições hipóxicas subsequentes afetam decisivamente a sobrevivência e funcionalidade das ilhotas. Objetivo Para diminuir o estresse sobre o enxerto, levando a um sucesso prolongado do transplante, propôs-se a adição de perfluorocarbono (PFC) ou laminina (LN), moléculas associadas respectivamente à oxigenação e interações célula-célula, ao biomaterial baseado em alginato, Biodritina, adequado ao encapsulamento celular. Metodologia Para testar a estabilidade das formulações PFC-Biodritina e LN-Biodritina, microcápsulas foram submetidas a diferentes estresses (rotacional, osmótico, temperatura e cultura) por 7 e 30 dias. A pureza do biomaterial foi avaliada pela coincubação com macrófagos murinos RAW264.7, por 3, 9 e 24h, quando a ativação dos macrófagos foi observada pela expressão gênica de IL- 1β e TNFα. Microcápsulas implantadas i.p. em camundongos foram recuperadas após 7 ou 30 dias, para análises de biocompatibilidade. A expressão de níveis de mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulina 1 e 2), proteínas (Bax, Bcl-XL e Xiap) e a atividade de Caspase3 foram avaliadas em ilhotas microencapsuladas com PFC- e LN-Biodritina, após cultura de 48h em condições de normóxia e hipóxia (<2% O2). Camundongos diabéticos foram transplantados com ilhotas encapsuladas nas diferentes formulações e os animais foram monitorados pelas variações de massa corporal, glicêmicas e pela funcionalidade do enxerto (TOTGs). As ilhotas foram recuperadas de animais normo ou hiperglicêmicos e uma análise de biocompatibilidade das cápsulas foi realizada, assim como a avaliação funcional das células-β...

Transplantation of microencapsulated islets represents an attractive therapeutical approach to treat type 1 Diabetes Mellitus, accounting for an improved glycemic control and the abolishment of immunosuppressive therapies. However, maintenance of long-term β-cell viability remains a major problem. During islet isolation, the loss of extracellular matrix interactions and the hypoxic conditions thereafter dramatically affect β-cell survival and function. Objective To lessen the burden of islet stress and achieve a better outcome in islet transplantation we tested the addition of perfluorocarbon (PFC) or laminin (LN), molecules associated respectively with oxygenation and cell-cell interaction, to Biodritin, an alginate-based material suitable for cell microencapsulation. Methodology To test the stability of PFC-Biodritin and LN-Biodritin composites, microcapsules were subjected to different stresses (rotational, osmotic, temperature and culture) for 7 and 30 days. To assess biomaterial purity microcapsules were co-incubated with RAW264.7 murine macrophage cell line for 3, 9 and 24h and macrophage activation was detected through mRNA levels of IL-1β and TNFα. Microcapsules were implanted i.p. in mice and retrieved after 7 or 30 days, for biocompatibility analyses. Gene expression at mRNA (bax, bad, bcl-2, bcl-XL, xiap, caspase 3, mcp1/ccl2, hsp70, ldh, insulin 1 and 2) and protein (Bax, Bcl-XL and Xiap) levels, together with Caspase3 activity, were evaluated in islets microencapsulated in PFC- or LN-Biodritin, upon culturing for 48h in normoxic or hypoxic (<2% O2) conditions. Diabetic mice were transplanted with PFC- or LN-Biodritin microencapsulated islets, followed by assessments of body weight, glycemia and graft function by oral glucose tolerance tests (OGTTs). Microencapsulated islets were retrieved from normoglycemic or hyperglycemic mice and biocompatibility analyses of the beads together with a functional assessment of the graft followed. After graft...

Immunological characteristics and pancreatic β-cell function in first-degree relatives of type 1 diabetes mellitus / 中华内分泌代谢杂志

Oral glucose tolerance test(OGTT)was performed in 419 first-degree relatives(FDRs)of type 1 diabetes mellitus. GADA, IA-2A, and IAA were determined by radioligand assay, and the positive rates were 7.16%, 1.43%, and 1.26%, respectively. Intravenous glucose tolerance test(IVGTT)and nateglinide-OGTT were performed in 39 controls, 11 first-degree relatives with positive autoantibody(Ab+group), 14 ones with negative autoantibody(Ab-group)during 5-7 days.The first-phase insulin release(FPIR), area under insulin release during 0-10 min [AUC0-10] of IVGTT and the value of(ΔI30/ΔG30)of nateglinide-OGTT in Ab+group were lower than those of control and(2.75±0.37 vs 3.61±1.05)mU/mmol, all P＜0.05]. The 1st min insulin release in Ab+group was lower than that of Ab-group [(3.80±0.30 vs 4.52±0.70)mU/L, P＜0.05]. The HOMA-IR was higher in Ab-group than that in control group(2.92±1.04 vs 1.96±1.22, P＜0.05). The results suggest that the positivity rates of autoantibodies in FDRs of type 1 diabetes mellitus are very close to those of Caucasian. There exist insulin secretion defects in FDRs with positive autoantibody while insulin resistance in FDRs with negative autoantibody.

Consistency of ocular coherence tomography fast macular thickness mapping in diabetic diffuse macular edema

OBJECTIVES: To investigate optical coherence tomography consistency on foveal thickness, foveal volume, and macular volume measurements in patients with and without diffuse diabetic macular edema. INTRODUCTION: Optical coherence tomography represents an objective technique that provides cross-sectional tomographs of retinal structure in vivo. However, it is expected that poor fixation ability, as seen in diabetic macular edema, could alter its results. Several authors have discussed the reproducibility of optical coherence tomography, but only a few have addressed the topic with respect to diabetic maculopathy. METHODS: The study recruited diabetic patients without clinically evident retinopathy (control group) and with diffuse macular edema (case group). Only one eye of each patient was evaluated. Five consecutive fast macular scans were taken using Ocular Coherence Tomography 3; the 6 mm macular map was chosen. The consistency in measurements of foveal thickness, foveal volume, and total macular volume for both groups was evaluated using the Pearson's coefficient of variation. The T-test for independent samples was used in order to compare measurements of both groups. RESULTS: Each group consisted of 20 patients. All measurements had a coefficient of variation less than 10 percent. The most consistent parameter for both groups was the total macular volume. DISCUSSION: Consistency in measurement is a mainstay of any test. A test is unreliable if its measurements can not be correctly repeated. We found a good index of consistency, even considering patients with an unstable gaze. CONCLUSIONS: Optical coherence tomography is a consistent method for diabetic subjects with diffuse macular edema.

OBJETIVOS: Investigar a consistência das medidas de espessura foveal, volume foveal e volume macular total feitas pela tomografia de coerência óptica em pacientes com e sem edema macular difuso diabético. INTRODUÇÃO: A tomografia de coerência óptica é uma técnica objetiva que proporciona tomografias seccionais da estrutura retiniana in vivo, entretanto, é esperado que uma baixa capacidade de fixação ocular, assim como observado nos casos de edema macular diabético, possa prejudicar os resultados deste exame.Vários autores já discutiram sobre a reprodutibilidade da tomografia de coerência óptica, entretanto, há pouca publicação deste assunto na maculopatia diabética. MÉTODOS: O estudo incluiu pacientes diabéticos sem evidências clínicas de retinopatia (grupo controle) e pacientes portadores de edema macular difuso diabético (grupo caso). Apenas um olho foi avaliado em cada paciente. Foram realizadas cinco medidas consecutivas com o protocolo "fast macular" do aparelho de tomografia de coerência óptica. Utilizou-se o mapa macular de 6 mm. A consistência das medidas de espessura foveal, volume foveal e volume macular total foi avaliada pelo teste do coeficiente de variação de Pearson. O teste T para amostras independentes foi utilizado para comparar as medidas entre os grupos. RESULTADOS: Cada grupo consistiu de 20 pacientes. Todas as medidas apresentaram um coeficiente de variação menor do que 10 por cento. O parâmetro mais consistente foi o volume macular total. DISCUSSÃO: A consistência é um quesito fundamental para qualquer teste. Caso as medidas de um determinado teste não possam ser corretamente repetidas, o resultado deste teste não pode ser considerado confiável. Nós observamos um alto índice de consistência da tomografia de coerência óptica, mesmo considerando portadores de fixação ocular instável. CONCLUSÕES: A Tomografia de coerência óptica é um teste consistente em portadores de edema macular difuso diabético.