TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Association of Vitamin D Deficiency with Diabetic Retinopathy in Young People with Type 1 Diabetes Mellitus

Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse effects.Hence measuring stress is of great importance.An algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in adults.However,it has never been investigated in children and adolescents.The aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D.Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits.Salivary cortisol,PPS and questionnaires were collected,measured,and answered on site.HbA1c was collected from medical files.We found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on age.Males scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in results.High PPS values indicated either measurement difficulties or hypersensibility towards pain.

Protective Effect of Silent Mating Type Information Regulation 2 Homolog 1 on TGF-β1 Pathway via mTOR in Diabetic Nephropathy

Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.

Association of XbaI GLUT1 Polymorphism with Susceptibility to Type 2 Diabetes Mellitus and Diabetic Nephropathy

Objectives: Diabetic nephropathy (DN) is one of the chronic microangiopathic complications of type 2 diabetes (T2DM) and has become the most frequent cause of end-stage renal disease. The XbaI polymorphism in the glucose transporter (GLUT1) has been suggested in the development of DN. We examined the association between XbaI polymorphism of GLUT1 and susceptibility to T2DM and development of DN. Methods: The study included 227 T2DM patients divided into 107 without DN (DM ? DN) and 120 with DN (DM + DN), in addition to 100 apparently healthy controls. Genotyping was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Results: The GLUT1 XbaI T allele was associated with increased susceptibility to T2DM, when comparing the healthy controls to the whole diabetic group, odds ratio (OR) = 1.899, 95% confidence interval (CI) (1.149 - 3.136), p = 0.011. This association was also significant between healthy controls and DM ? DN OR = 1.997 (1.079 - 3.699), p = 0.026 as well as between healthy controls and DM + DN OR = 1.818 (1.016 - 3.253), p = 0.042. However there was no significant association of XbaI polymorphism with DN when comparing DM ? DN to DM + DN OR = 0.910 (0.474 - 1.747), p = 0.777. Conclusion: XbaI T allele is associated with increased susceptibility to T2DM, but not to development of DN. Further studies are needed to replicate such findings.

Association between Hyperhomocysteinemia and Microangiopathic Complications (Neuropathy and Nephropathy) in Subjects with Type 1 and Type 2 Diabetes

This prospective case-control study aimed to assess the prevalence of hyperhomocysteinemia and explore its potential correlation with microangiopathic complications, specifically nephropathy and neuropathy, in a cohort of both type 1 and type 2 diabetic patients. Conducted at the Marc Sankalé Center of Abass Ndao Hospital in Dakar from June to September 2018, the study enrolled a total of 106 diabetic patients, comprising 93 type 2 diabetics and 13 type 1 diabetics, who were matched with control subjects free from clinically detectable pathologies, based on sex and age ± 2 years. The mean age of type 1 and type 2 diabetic patients was 24.46 ± 8.41 years and 57.28 ± 11.28 years, respectively. Our findings revealed a statistically significant elevation in mean homocysteine levels among patients when compared to controls (12.63 vs. 9.88;p < 0.0001). Hyperhomocysteinemia was observed in 24.5% of the patients, exclusively among those with type 2 diabetes. Within the hyperhomocysteinemia subgroup, 58% were male, and 42% were female. The analysis of neuropathy and nephropathy frequencies among type 2 diabetic patients, stratified by homocysteine concentrations, demonstrated a notably higher prevalence of diabetic nephropathy in patients with hyperhomocysteinemia compared to those with normohomocysteinemia (23.07% vs. 8.75%;p = 0.052). Similarly, diabetic neuropathy exhibited a significantly greater frequency in patients with hyperhomocysteinemia as opposed to normohomocysteinemia (80.76% vs. 50%;p = 0.005). Furthermore, our results established a significant positive correlation between homocysteine concentrations and both age (r = 0.402;p < 0.0001) and creatinine levels (r = 0.461;p < 0.0001). Bivariate logistic regression analysis indicated that patients with hyperhomocysteinemia faced 3 times and 6 times higher risks of developing neuropathy (OR = 3.5;p = 0.061) and diabetic nephropathy (OR = 6.092;p = 0.014), respectively.

Association of GA/HbA1c Ratio with Diabetic Retinopathy

Objectives: The aim of this study was to explore the potential correlation between the GA/HbA1c ratio and diabetic retinopathy (DR) in patients with type 2 diabetes (T2D), as the GA/HbA1c ratio serves as a marker for glycemic variability. Methods: A total of 2565 T2D patients were included in this study and grouped into five categories based on the diagnostic criteria for DR. We examined the impact of the GA/HbA1c ratio on the progression of diabetes. Results: The non-DR group exhibited lower GA/HbA1c levels compared to the DR group. Additionally, as the severity of DR increased among the five groups, there was a corresponding increase in the GA/HbA1c ratio. Logistic regression analysis demonstrated that the GA/HbA1c ratio independently elevated the risk of DR occurrence. Conclusions: The GA/HbA1c ratio can independently predict the occurrence and progression of diabetic retinopathy.

Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats

Diabetic nephropathy is a major cause of end-stage renal disease （ESRD） in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin （90 mg/kg） in neonatal rats and then these rats were treated with rosiglitazone （1.0 mg/kg） in combination with glimepiride （0.5 mg/kg） or with pioglitazone （2.5 mg/kg） in combination with glimepiride （0.5 mg/kg）. Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.

Evaluation of the Serum Levels of IL-1 in Type 2 Diabetic Patients with and without Diabetic Nephropathy

Background: Diabetic nephropathy (DN) has been regarded as an important cause of morbidity in patients with type 2 diabetes (T2D). Immune system components are modulated during T2D, with the most apparent modifications in adipose tissue, pancreatic islets, liver, and circulating leukocytes. The aim of this survey was to evaluate the role of IL-1 in the etiopathogenesis of nephropathic T2D. Methods: In this case-control investigation, the study population consisted of 58 T2D patients with proteinuria (nephropathy T2D cases) as the case group and 76 T2D cases without proteinuria (non-nephropathy T2D cases) as the control group. Blood samples were obtained from all individuals and ELISA approach was carried out to measure IL-1 levels in samples. Results: Our experiments demonstrated that T2D patients with nephropathy had significantly increased levels of IL-1 in their blood in comparison to T2D patients without nephropathy. Conclusions: It seems that IL-1 plays a role in the etiopathogenesis of nephropathy in T2D patients, requiring further implementation to vivid disclose of the inflammation in this context.

Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients

BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.

Lipocalin-2 as a biomarker for diabetic nephropathy

Diabetes is a major global public health issue.The prevalence of type 1 diabetes is comparatively static,as hereditary and genetic causes are involved,while type 2 diabetes(T2D)prevalence is increasing day by day.T2D is associated with chronic complications,including diabetic neuropathy(DN),nephropathy,retinopathy,and other complications like diabetic foot.DN is the main complication of both types of diabetes.DN can be diagnosed by routine laboratory tests,microalbuminuria>300 mg/24 h,and a gradual decrease in glomerular filtration rate.As the appearance of microalbuminuria is a late manifestation,an early marker for renal damage is needed.Lipocalin-2,also known as neutrophil gelatinaseassociated lipocalin(NGAL),is a small protein purified from neutrophil granules and a good marker for kidney disease.NGAL is a transporter protein responsible for many physiological processes,such as inflammation,generation of the immune response,and metabolic homeostasis.NGAL has been reported to depict the early changes in renal damage when urine microalbumin is still undetecable.Therefore,elucidating the role of NGAL in detecting DN and understanding its mechanism can help establish it as a potential early marker for DN.

Meta- analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

AIM: To collectively evaluate the association of intercellular adhesion molecule-1(ICAM-1) gene K469 E polymorphism(rs5498) with diabetic retinopathy(DR) in patients with type 2 diabetic mellitus(T2DM). METHODS: Overall review of available literatures relating K469 E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios(ORs). Potential sources of heterogeneity and bias were explored.RESULTS: Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469 E polymorphism with DR(P 】0.05). A statistically significant association was detected between the K469 E polymorphism and proliferative DR(PDR) in Asians only in dominant model(GG+AG vs AA) with pooled OR of 0.729(95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model(AG +AA vs GG;OR=1.178, 95%CI: 0.898-1.545, P =0.236, P heterogeneity=0.248)or allelic model(G vs A; OR=0.769, 95% CI: 0.576-1.026,P =0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg’s and Egger’s test. CONCLUSION: This research found no statistically significant association between ICAM-1 gene K469 E polymorphism and DR in patients with T2 DM, but showed significant association of the K469 E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

Is there a role for glucagon-like peptide-1 receptor agonists in the management of diabetic nephropathy?

Chronic kidney disease constitutes a major microvascular complication of diabetes mellitus.Accumulating data suggest that glucagon-like peptide-1 receptor agonists(GLP-1 RAs)might have a role in the management of diabetic kidney disease(DKD).GLP-1 RAs appear to reduce the incidence of persistent macro-albuminuria in patients with type 2 diabetes mellitus.This beneficial effect appears to be mediated not only by the glucose-lowering action of these agents but also on their blood pressure lowering,anti-inflammatory and antioxidant effects.On the other hand,GLP-1 RAs do not appear to affect the rate of decline of glomerular filtration rate.However,this might be due to the relatively short duration of the trials that evaluated their effects on DKD.Moreover,these trials were not designed nor powered to assess renal outcomes.Given than macrolbuminuria is a strong risk factor for the progression of DKD,it might be expected that GLP-1 RAs will prevent the deterioration in renal function in the long term.Nevertheless,this remains to be shown in appropriately designed randomized controlled trials in patients with DKD.

Effect of Ethanol Extract of Rhodiola Rosea on the Early Nephropathy in Type 2 Diabetic Rats

Summary： This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy （DN）. The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin （STZ）. Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Cap- topril group. Oral glucose tolerance test （OGTT） was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose （FBG）, total cholesterol （TC）, triglyceride （TG）, creatinine clearance rate （Ccr）, 24-h urinary albumin （UA）, the ratio of kidney mass/body weight （renal index） and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor （TGF）-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of con- trol group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.

Female Preponderance in the Discordant Association between Retinopathy and Nephropathy in Patients with Type 2 Diabetes Mellitus

Aim: To elucidate clinical features in patients with type 2 diabetes with advanced retinopathy but without nephropathy. Methods: This study examined 1324 patients (784 males and 540 females) with type 2 diabetes mellitus. Diabetic reti-nopathy was graded according to the International Clinical Classification of Diabetic Retinopathy as no diabetic reti-nopathy, mild or moderate non-proliferative diabetic retinopathy, severe non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy. Diabetic nephropathy was classified into four stages of severity according to the Guideline Committee of the Japan Diabetes Society. Each patient was examined for retinopathy grade and nephropathy stage. Clinical features of patients with proliferative diabetic retinopathy were compared with regard to the four grades of diabetic nephropathy. Results: Fifty-two patients with type 2 diabetes (3.9% of the whole series of 1324 patients with type 2 diabetes and 25.7% of patients with proliferative diabetic retinopathy) had proliferative diabetic retinopathy without the presence of nephropathy. Multiple statistical analysis using a proportional odds model revealed that pa-tients with proliferative diabetic retinopathy without nephropathy had a significantly lower systolic blood pressure (p < 0.001) than those who did and were preponderantly female (p < 0.05). Conclusions: A possible susceptibility of dia-betic females to proliferative advanced retinopathy without nephropathy encourages further studies on the role of hor-mones and blood coagulation in the pathogensis of proliferative diabetic retinopathy.

The Outpatient Clinic Visit: Expectations and Fulfilment of Perceived Needs in Adolescents with Type 1 Diabetes

Background: To make outpatient visits for adolescents with diabetes successful, it is important for health care professionals to meet the adolescents’ needs and wishes. Aims: The aim is to investigate adolescents’ expectations of an outpatient diabetes clinic visit in comparison to what was deemed to be delivered and contrast this outcome in adolescents with self-reported high- and low-diabetes distress respectively. Methods: All adolescents in Sweden with type 1 diabetes, aged 15 to 18 years, were identified via The National Pediatric Diabetes Registry (SWEDIABKIDS) and asked to complete an online questionnaire regarding their expectations and the support received during the outpatient diabetes clinic visit. Results: 453 adolescents completed the survey. Boys’ expectations of discussion topics were mainly met while girls, especially those with diabetes distress, felt their discussion needs were not met regarding quality-of-life aspects. Conclusions: Although adolescents’ expectations are in general met during the diabetes outpatient clinic visit, aspects related to living with diabetes are not being met especially among female adolescents who reported diabetes distress. This study shows a gender difference both regarding expected discussion topics and what was deemed covered. Practice Implications: A multi-professional, individual person-centred care approach is needed at the diabetes outpatient clinic. This paper proposes that agenda setting performed by the adolescent, and agreed by the physician, prior to the outpatient clinic visit could facilitate individualized care and better meet the adolescents’ needs in a shared decision-making process.

Disordered eating behaviour and eating disorder among adolescents with type 1 diabetes:An integrative review

BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behaviour and eating disorders among adolescents with DT1.METHODS An integrative review was accomplished based on the following databases:PubMed,LILACS,CINAHL,Scopus,Web of Science,and Reference Citation Analysis(RCA),including publications in Portuguese,English,or Spanish,without time limit and time published.RESULTS The main instruments to evaluate disordered eating behaviour were The Diabetes Eating Problem Survey-Revised,The Diabetes Eating Problem Survey,and the eating attitudes test-26,and for eating disorders the main instruments used were The Bulimic Investigation Test of Edinburgh,The Binge Eating Scale,The Child Eating Disorder Examination,The five questions of the(Sick,Control,One,Fat and Food),and The Mind Youth Questionnaire.These instruments showed an effect in evaluating risks regarding nutritional habits or feeding grievances,with outcomes related to weight control,inadequate use of insulin,and glycaemia unmanageability.We did not identify publication bias.CONCLUSION Around the world,the most used scale to study the risk of disordered eating behaviour or eating disorder is The Diabetes Eating Problem Survey-Revised.International researchers use this scale to identify high scores in adolescents with DT1 and a relationship with poorer glycemic control and psychological problems related to body image.

儿童青少年1型糖尿病患儿发生酮症酸中毒的危险因素分析及预测模型的建立

目的研究儿童青少年1型糖尿病(type 1 diabetes mellitus,T1DM)发生糖尿病酮症酸中毒(diabetic ketoacidosis,DKA)的危险因素,并建立DKA风险预测模型,以期降低该类患儿DKA的发生率,提高患儿生存质量。方法回顾性选择2018年1月—2021年12月宁夏医科大学总医院收治的217例T1DM患儿,其中169例发生DKA患儿为DKA组,48例未发生DKA患儿为非DKA组。分析T1DM患儿发生DKA的危险因素,并建立预测T1DM患儿发生DKA风险的列线图模型。结果217例T1DM患儿中DKA发生率为77.9%(169/217)。多因素logistic回归分析显示,T1DM患儿入院随机血糖高、糖化血红蛋白高(hemoglobin A1c,HbA1c)、血酮高、甘油三酯高与发生DKA密切相关(分别OR=1.156、3.203×10^(15)、20.131、9.519,P<0.05)。列线图预测模型C-统计量为0.95,列线图模型预测T1DM患儿发生DKA的风险与实际发生DKA的风险平均绝对误差为0.004,说明模型整体预测能力较好。结论高入院随机血糖、高HbA1c、高血酮、高甘油三酯与儿童青少年T1DM发生DKA密切相关,应制定针对性干预措施,以降低T1DM发生DKA的风险。

Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population

Type 1 diabetes mellitus(T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1 DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1 DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1 DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1 DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.