Release of the angiogenesis inhibitor angiostatin in patients with proliferative diabetic retinopathy: association with retinal photocoagulation

Aims/hypothesis. Proliferative diabetic retinopathy is a major debilitating disease causing most cases of blindness in humans in the Western world. Photocoagulation is the established therapy of proliferative diabetic retinopathy, although the molecular mechanisms of its effects are still not known. Recently angiostatin has been characterized as a potent inhibitor of neovascularization. Apart from a possible down-regulation of angiogenic cytokines, release of angiostatin could initiate the anti-angiogenic effects of retinal photocoagulation.¶Methods. We investigated the regulation of angiostatin and the angiogenic cytokines vascular endothelial growth factor and basic fibroblast growth factor in vivo by comparing vitreal concentrations of 18 control patients and 34 patients with proliferative diabetic retinopathy with and without previous photocoagulation. Concentrations of basic fibroblast growth factor and angiostatin were additionally measured in serum, while vascular endothelial growth factor is known to be regulated locally in the eye. Cytokines were measured by immunological methods.¶Results. Angiostatin could be detected in 2 out of 18 control patients and in 25 out of 34 diabetic patients (p < 0.00 001). Most importantly, production of angiostatin in human vitreous correlated significantly with previous retinal photocoagulation (p < 0.0001) in patients with proliferative diabetic retinopathy. Only two patients (one control and one diabetic) had detectable serum concentrations of angiostatin. Additionally patients with proliferative diabetic retinopathy and with previous photocoagulation had significantly lower concentrations of vascular endothelial growth factor (0.9 ± 0.1 ng/ml; p < 0.0001) than diabetic patients without previous photocoagulation (4.0 ± 0.8 ng/ml). The investigation of vitreal and serum basic fibroblast growth factor concentrations yielded no significant differences between the groups.¶Conclusion/interpretation. Angiostatin is not a regularly expressed angiogenesis inhibitor in human vitreous. The alterations we observed suggest that local release of angiostatin and down-regulation of vascular endothelial growth factor mediate the therapeutic effects of retinal photocoagulation in proliferative diabetic retinopathy. [Diabetologia (2000) 43: 1404–1407]     

Regulation of glucose transporter (GLUT 3) and aldose reductase mRNA in bovine retinal endothelial cells and retinal pericytes in high glucose and high galactose culture

Summary The regulation of GLUT-3 and aldose reductase mRNA in retinal endothelial cells and retinal pericytes was studied in response to variations in the extracellular concentration of hexoses. In physiological concentrations of glucose (5 mmol/l), an increase in the level of GLUT-3 mRNA was observed in cultured cells compared to the level of mRNA found in the absence of glucose. In contrast, there was little change in the level of GLUT-3 mRNA when the cells were cultured in the presence of 5 mmol/l galactose. In high concentrations of glucose, there was a decline in GLUT-3 mRNA indicating that the GLUT-3 mRNA is regulated by the extracellular concentration of glucose. In contrast, at both 5 mmol/l and 25 mmol/l glucose, the level of aldose reductase mRNA was increased. Furthermore, there were differences in the magnitude of the increase of aldose reductase mRNA between bovine retinal pericytes and bovine retinal endothelial cells with a greater increase being observed in the pericytes. We propose that this demonstration of a facultative glucose transporter system within retinal cells, and in particular the specific response to different hexoses and the known distinct kinetic parameters of the transporter system in specific cell types, highlights the heterogeneity of hexose transport mechanisms in retinal cells. Thus, hypergalactosaemia as a model system for the study of diabetic retinopathy should be used with caution.     

芍药苷对脂多糖诱导的THP-1细胞炎症因子分泌和ABCA1表达的影响

目的观察芍药苷(PF)对脂多糖(LPS)诱导的THP-1细胞炎症因子和三磷酸腺苷结合盒转运体A1(ABCA1)表达的影响。方法用含PF(10-8、10-7、10-6、10-5、10-4mol/L)培养基预处理细胞0.5 h,再用含LPS(1mg/L)培养基共同培养细胞24 h。ELISA检测细胞培养液上清中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)水平,Western blot检测细胞中ABCA1蛋白的表达。结果与对照组比较,LPS组细胞上清液中IL-1β、IL-6、IL-8和TNF-α的水平显著性升高(P0.05),ABCA1蛋白表达显著性下调(P0.05)。与LPS组比较,LPS+PF(10~(-6)、10~(-5)和10~(-4)mol/L)组上清液中IL-1β、IL-6、IL-8和TNF-α的水平显著性降低(均P0.05),ABCA1蛋白表达显著性上调(P0.05),呈现浓度依赖性。结论芍药苷抑制LPS诱导的THP-1细胞炎症因子分泌和ABCA1表达下调。     

Evaluation of a combination digital retinal camera with spectral-domain optical coherence tomography (SD-OCT) that might be used for the screening of diabetic retinopathy with telemedicine: A pilot study

Aims

Pilot study to determine whether an instrument combining a non-mydriatic retinal camera and spectral domain optical coherence tomography (SD-OCT) is effective for screening patients with diabetic retinopathy (DR).

Prevalence of sleep apnoea in patients with type 1 diabetes and its association with comorbidities and diabetic complications: A French nationwide prospective study

Aim

To investigate sleep apnoea prevalence, factors influencing severity, and associations between sleep apnoea severity and micro-/macrovascular complications in a large population of patients with type 1 diabetes.

Materials and methods

This French multicentre prospective cohort study was conducted between July 2016 and June 2020. Adults with type 1 diabetes using an insulin pump were eligible. Home care provider nurses collected demographic and clinical data and set up oximetry to determine the oxygen desaturation index (ODI). No, mild–moderate and severe sleep apnoea were defined as ODI <15 events/h, 15 to <30 events/h and ≥30 events/h, respectively. Univariate and multivariate analyses were performed to identify factors associated with sleep apnoea, and associations between sleep apnoea severity and micro-/macrovascular complications were determined using logistic regression.

Results

Of 769 participants, 12.4% and 3.4% had mild-to-moderate or severe sleep apnoea, respectively. Factors significantly associated with sleep apnoea on multivariate analysis were age, sex, body mass index (BMI) and hypertension. After adjustment for age, sex and BMI, presence of severe sleep apnoea was significantly associated with macrovascular complications (odds ratio vs. no sleep apnoea: 3.96 [95% confidence interval 1.43-11.11]; P < 0.01), while mild-to-moderate sleep apnoea was significantly associated with presence of diabetic retinopathy (odds ratio 2.09 [95% confidence interval 1.10-3.74]; P < 0.01).

Conclusion

Sleep apnoea is a significant comorbidity in patients with type 1 diabetes, especially with respect to diabetic complications. This highlights the need for sleep apnoea screening and management in these individuals.     

Long-acting insulin analogues and the risk of diabetic retinopathy among patients with type 2 diabetes: A population-based cohort study

Aim

To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes.

Methods

Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin.

Results

There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR.

Conclusions

Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.     

Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.

AIMS: To evaluate serum levels of vascular endothelial growth factor (VEGF) in a large group of children, adolescents and young adults with Type 1 diabetes mellitus to investigate whether increased VEGF concentrations are associated with long-term glycaemic control and microvascular complications. METHODS: The study involved 196 patients with Type 1 diabetes mellitus (age range 2-24 years, onset of diabetes before the age of 12 years, duration of disease longer than 2 years), without clinical and laboratory signs of microvascular complications; they were divided into three groups (group 1 - n = 37, age < 6 years; group 2 - n = 71, age 6-12 years; group 3 - n = 88, age > 12 years). Fifty-three adolescents and young adults (age 16.1-29.7) with different grades of diabetic retinopathy and microalbuminuria were also selected (group 4). A total of 223 healthy controls were matched for age and sex with each group of patients with diabetes mellitus. RESULTS: VEGF serum levels were significantly increased in pre-school and pre-pubertal children with diabetes as well as in pubertal patients compared to controls. VEGF concentrations were markedly increased in adolescents and young adults with microvascular complications compared with both healthy controls and diabetic patients without retinopathy or nephropathy. Multivariate analysis showed that elevation of VEGF in serum was an independent correlate of complications. One-year mean HbA1c values were significantly correlated with VEGF concentrations (r = 0.372; P < 0.01). Children with HbA1c levels greater than 10% had significantly higher VEGF concentrations when compared with matched patients whose HbA1c levels were lower than 10%. In poorly controlled diabetic children (HbA1c > 10%), long-term (2 years) improvement of glycaemic control (aiming at HbA1c < 7%) resulted in a significant reduction of VEGF levels. CONCLUSIONS: VEGF serum concentrations are increased in prepubertal and pubertal children with diabetes. Glycaemic control influences VEGF serum levels. Severity of microvascular complications is associated with marked increase of VEGF concentrations in the serum of these patients.     

人脐血干细胞移植对心肌梗死大鼠血管新生和血管内皮生长因子、促血管生成素-1表达的影响

目的观察人脐血干细胞(hUCBSC)经静脉移植对心肌梗死(MI)大鼠血管新生和血管内皮生长因子(VEGF)、促血管生成素(Ang-1)表达的影响。方法雄性Sprague-Dawley大鼠40只,随机分为3组:(1)假手术组(10只):大鼠麻醉后开胸,将结扎线通过前降支动脉(LAD),不结扎,然后关胸;(2)对照组(15只):大鼠麻醉后开胸,结扎LAD,制备MI模型成功(经肉眼观察和心电图证实)后,经尾静脉注射0.9%生理盐水0.5 mL;(3)移植组(15只),大鼠麻醉后开胸,结扎LAD,制备MI模型后,经尾静脉注射hUCBSC 0.5 mL(含干细胞2×107/mL,由北京市脐血干细胞库提供)。术后4周行超声心动图检查和心导管检查,并取心脏组织行HE染色、抗Ⅷ因子免疫组化染色,观察心肌病理改变、肌毛细血管密度(MCD)的变化。同时用免疫组化和RT-PCT的方法检测VEGF、Ang-1及其mRNA的表达。结果与对照组相比,术后4周时移植组左室射血分数较对照组明显改善(55.35%±11.23%比40.23%±10.87%,P<0.01),左室舒张末压显著降低(10.56±4.69 mmHg比20.13±5.63 mmHg,P<0.01),而左室压力最大变化率明显增加(4.25±2.01 mmHg比6.53±2.38mmHg,P<0.05;3.83±2.69 mmHg比6.25±2.92 mmHg,P<0.05);移植组MCD明显高于对照组(每高倍视野4.2±0.5个比2.1±0.3个,P<0.01);移植组VEGF和Ang-1及其mRNA表达明显高于对照组和假手术组。结论经静脉移植hUCBSC促进MI大鼠VEGF和Ang-1表达,促进血管新生,改善心功能。     

LncRNA NEAT1 promotes proliferation of ovarian cancer cells and angiogenesis of co-incubated human umbilical vein endothelial cells by regulating FGF9 through sponging miR-365: An experimental study

Objective:To uncover the function of lncRNA NEAT1 in ovarian cancer (OC) cells and its mechanism.Methods:The expression patterns of lncRNA NEAT1 and FGF9 in human OC cells and human ovarian epithelial cells was determined. OC cells were transfected with sh-NEAT1, pcDNA3.1-NEAT1, miR-365 mimic, miR-365 inhibitor or pcDNA3.1-NEAT1 + sh-NEAT1 before cell proliferation rate and cell clone formation rate were measured. After the transfected OC cells were co-cultivated with human umbilical vein endothelial cells (HUVECs), Matrigel angiogenesis assay tested angiogenesis of HUVECs; qRT-PCR and Western blot tested the expressions of vascular endothelial growth factor (VEGF), angiogenin 1 (Ang-1) and matrix metalloproteinase 2 (MMP2). Dual-luciferase reporter assay determined the targeted binding of NEAT1 and FGF9 to miR-365.Results:LncRNA NEAT1 and FGF9 are over-expressed in OC cells. Knockdown of NEAT1 or FGF9, or over-expression of miR-365 results in decreased proliferation rate and cell clones as well as inhibited angiogenesis and down-regulated expressions of VEGF, Ang-1 and MMP2. Over-expression of NEAT1 or knockdown of miR-365 can reverse the effect caused by FGF9 knockdown. NEAT1 can down-regulate the expression of miR-365 while up-regulating that of FGF9. Dual-luciferase reporter assay determined that NEAT1 competes with FGF9 for binding to miR-365.Conclusion:LncRNA NEAT1 up-regulates FGF9 by sponging miR-365, thus promoting OC cell proliferation and angiogenesis of HUVECs.     

A study of the effects of human blood derivatives and individual growth factors on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells

Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [³H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED₅₀= 1.8×10^–13 mol/l), acidic fibroblast growth factor (7.4× 10^–12 mol/l), insulin-like growth factor 1 (8.6×10^–10 mol/l), insulin (158 U/ml) and endothelin-1 (6.1×10^–10 mol/l). Transforming growth factor ₁ inhibited DNA synthesis (ID₅₀=3.6×10^–10 mol/l) and so did heparin (1.4×10^–6 mol/l) and low molecular weight heparin (2.9×10^–6 mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2×10^–13 mol/l) and acidic fibroblast growth factor (1.3×10^–9 mol/l), and inhibited by transforming growth factor ₁, (1.6×10^–12 mol/l). Neither cell type was stimulated by platelet-derived growth factor (A+B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma. Some, though, may play a role in the regulation of pericyte turnover through paracrine mechanisms which should be further investigated.     

Results from the Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study: A brief report of kidney and inflammatory outcomes

Youth with type 1 diabetes (T1D) demonstrate insulin resistance, independently of glycaemia, when compared to normoglycaemic peers. Insulin resistance increases the risk of cardiovascular disease and diabetic kidney disease, factors also associated with systemic inflammation. We evaluated the effect of metformin on markers of inflammation and diabetic kidney disease in adolescents with T1D. EMERALD, a double-blind, randomized, placebo-controlled trial of 3 months of metformin in 48 participants aged 12–21 years with T1D, included baseline and follow-up assessments of serum creatinine and cystatin C to estimate glomerular filtration rate (eGFR), aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, white blood count, platelets, adiponectin, leptin, and urine albumin: creatinine ratio (UACR). Metformin was associated with a 13.9 mL/min/1.73 m² (95% confidence interval 4.7–23.1 mL/min/1.73 m²) increase in estimated GFR by serum creatinine versus placebo (P ≤ 0.01), with a significant difference remaining after multivariable adjustments (P = 0.03). Whereas eGFR measured by serum creatinine increased significantly after metformin treatment, no differences were observed in cystatin C, UACR, or systemic inflammatory markers. Additional studies with directly measured GFR in response to metformin in T1D are needed.     

Association between glycaemia risk index (GRI) and diabetic retinopathy in type 2 diabetes: A cohort study

Aim

To investigate the association between a new composite metric, glycaemia risk index (GRI), and incident diabetic retinopathy (DR).

Methods

A total of 1204 adults with type 2 diabetes without DR at baseline were included between 2005 and 2019 from a single centre in Shanghai, China. GRI was obtained from continuous glucose monitoring data at baseline. Cox proportion hazard regression analysis was used to assess the association between GRI and the risk of incident DR.

Results

During a median follow-up of 8.4 years, 301 patients developed DR. The multivariable-adjusted hazard ratios (HRs) for incident DR across ascending GRI quartiles (≤14 [reference], 15 ~ 28, 29 ~ 47 and > 47) were 1.00, 1.05 (95% CI 0.74-1.48), 1.33 (95% confidence interval [CI] 0.96-1.84) and 1.53 (95% CI 1.11-2.11), respectively. For each 1-SD increase in GRI, the risk of DR was increased by 20% (HR 1.20, 95% CI 1.07-1.33) after adjustment for confounders.

Conclusions

In patients with type 2 diabetes, higher GRI is associated with an increased risk of incident DR. GRI has the potential to be a valuable clinical measure, which needs to be further explored in future studies.     

缺氧诱导因子-1α表达与胰腺癌病理学特征及新生血管生成的关系

目的　研究胰腺癌组织中缺氧诱导因子 - 1α(HIF- 1α)的表达与胰腺癌病理学特征的关系 ,以及 HIF- 1α表达与血管内皮生长因子 (VEGF)和肿瘤微血管密度 (MVD)之间的相互关系。方法　应用免疫组织化学方法检测 4 7例胰腺癌和 10例正常胰腺组织中 HIF- 1α和 VEGF蛋白的表达。同时用CD34单克隆抗体标记胰腺癌和正常胰腺组织中的微血管。结果　 HIF- 1α和 VEGF蛋白在 4 7例胰腺癌组织中的阳性表达率分别为 5 5 .3% (2 6 / 4 7)和 6 1.7% (2 9/ 4 7) ,而在 10例正常胰腺组织中均未见表达。胰腺癌组织 MVD为 37.6 1± 14 .3,正常胰腺组织为 7.5 5 ± 2 .4 ,二者间有显著性差别 (t'=13.5 1,P<0 .0 0 1)。 HIF- 1α和 VEGF蛋白阳性表达率及 MVD均与胰腺癌的浸润和转移密切相关 (χ2 =4 .32 ,6 .0 1,4 .75 ,4 .6 2 ;t=2 .38,3.92 ;P<0 .0 5 ) ,而与胰腺肿块大小、组织学分级和患者术后 1年生存率无关 (P>0 .0 5 )。HIF- 1α与 VEGF(r=0 .32 9,χ2 =5 .71;P<0 .0 5 )、HIF- 1α与 MVD(r=0 .5 94 ,t=4 .96 ;P<0 .0 0 1)及 VEGF与 MVD(r=0 .36 6 ,t=2 .6 4 ;P<0 .0 5 )间在胰腺癌组织中的表达均呈显著的正相关性。结论　在缺氧状态下 ,胰腺癌组织中 HTF- 1α基因被激活 ,过量表达 HIF- 1α蛋白 ,并通过诱导 VEGF     

Vesicular monoamine transporter,type 2 (vmat2) expression as it compares to insulin and pancreatic polypeptide in the head,body and tail of the human pancreas

The vesicular monoamine transporter, type 2 (VMAT2) is responsible for sequestering monoamine neurotransmitters into exocytic vesicles in neurons, enterochromaffin-like cells of the stomach and cells arising from the common myeloid progenitor. VMAT2 is also present in the pancreas and is expressed by insulin producing β cells, but not by glucagon or somatostatin expressing islet cells. Positron emission tomography (PET) targeting of VMAT2 is currently being evaluated as a non-invasive tool to measure β cell mass (BCM) in living humans. In recent trials, PET measurements of VMAT2 in the pancreas overestimated BCM in type 1 diabetes (T1D) patients predicted to have little to no BCM by metabolic measures. Recently, tissue immunohistochemistry studies suggested that VMAT2 staining may also co-localize with pancreatic polypeptide (PP) staining cells in pancreas tissue, but these studies were not quantitative. In this report, we evaluated VMAT2 specificity for β cells in sub-regions of the human pancreas using antibodies targeting VMAT2, insulin and PP by double-label immunofluorescence. Immunostaining for VMAT2 and insulin demonstrated 89 ± 8% overlap in the body and tail of the pancreas. However, 44 ± 12% and 53 ± 15% of VMAT2 cells co-stained with PP- and insulin-staining cells, respectively in the pancreatic head. Significant co-staining for VMAT2 and PP cells in the head of the pancreas may partly explain the apparent overestimation of BCM in T1D by PET. Specific targeting of the pancreatic body and tail using VMAT2 PET scanning may reflect BCM more accurately.     

Effect of sodium-dependent glucose transporter inhibitors on glycated hemoglobin A1c after 24 weeks in patients with diabetes mellitus: A systematic review and meta-analysis

Background:To evaluate dapagliflozin, canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin according to their effect on the glycated hemoglobin A1c (HbA1c) level in patients with type 2 diabetes mellitus.Methods:The Web of Science, PubMed, Cochrane Library, EMBASE, and Clinical Trials databases were electronically searched to collect randomized controlled trials of patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used to perform the meta-analysis and to create plots.Results:Finally, 27 studies were selected and included in this study. The meta-analysis results showed that sodium-dependent glucose transporter (SGLT) inhibitors significantly reduced the HbA1c level in patients with type 2 diabetes mellitus. However, these results were highly heterogeneous, so we conducted a subgroup analysis. The results of the subgroup analysis suggested that by dividing populations into different subgroups, the heterogeneity of each group could be reduced.Conclusions:SGLT inhibitors had a good effect on the HbA1c level in patients with type 2 diabetes mellitus, but there might be differences in the efficacy of SGLT inhibitors in different populations. It is hoped that more studies will be conducted to evaluate the efficacy and safety of SGLT inhibitors in different populations.Registration Number:CRD42020185025.     

Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide,multicentre, cross-sectional study

Aims

This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes.

Materials and Methods

This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency.

Results

IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD.

Conclusions

IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.

     

Predictors of renal complications in pediatric patients with type 1 diabetes mellitus: A prospective cohort study

Aims

Diabetic Nephropathy (DN) is rarely encountered in childhood, otherwise early subclinical abnormalities are detectable few years after diabetes diagnosis. Our aim was to evaluate the incidence rate of microalbuminuria in childhood onset type 1 diabetes (DM1) patients. Secondary aim was to examine which variables could influence the development of DN.