Glycemic variability and time in range among children with type 1 diabetes on insulin pump during the Covid-19 pandemic in Egypt; single center experience.

BACKGROUND: Covid-19 has impacted the lives of individuals worldwide especially those with chronic illnesses. Children with type 1 diabetes (T1DM) are at risk of glycemic deterioration during the Covid-19 pandemic. However, some studies reported glycemic improvement in these children during the pandemic. AIM: To assess the impact of Covid-19 on glycemic control and acute complications among children with T1DM on insulin pump in Egypt. METHODOLOGY: Forty-two children with T1DM on insulin pump for at least 1 year were assessed during the period from June 2020 to May 2021 for insulin requirements, insulin-pump problems, frequency of diabetic-ketoacidosis (DKA), hypoglycemia and HbA1C. Continuous-glucose monitoring was done using Medtronic i-pro device for 5 days. Data were compared to those obtained from the patients' medical records 1 year previously. RESULT: Upon comparing data during Covid-19 pandemic with previous data from 12-24 months before Covid-19, there was a significant small increase in the mean total daily insulin dose from 0.83 ± 0.28 to 0.88 ± 0.30 U/kg/day with a similar small increase in the mean basal percentage from 51.19 ± 3.46 to 52.74 ± 4.31. Interestingly, the median time in range showed small increase from 53 (IQR 47-61) to 57.0 (IQR 51-73), the mean coefficient of variation showed small decrease from 42.10 ± 9.90 to 38.20 ± 8.12 and the mean HbA1C significantly decreased from 8.8 ± 1.3 (72.31 ± 16.78 mmol/ml) to 7.8 ± 1.2 mg/dl (61.31 ± 16.62 mmol/mol). Twenty-nine children (69%) had insulin-pump problems in the form of skin irritation (31%), skin infection (7.1%) and pump Set/Site occlusion (31%). CONCLUSION: No safety issues and overall glycemic improvement were reported among the children with T1DM on insulin pump therapy from this single center during the covid-19 pandemic.

The efficacy of insulin degludec and insulin glargine over NPH insulin among toddlers and preschoolers with type 1 diabetes using glycemic variability and time in range.

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group. CONCLUSION: Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group. WHAT IS KNOWN: • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic. WHAT IS NEW: • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Changes in early optical coherence tomography angiography among children and adolescents with type 1 diabetes: Relation to fibroblast growth factor 21.

AIMS: Current diagnostic and treatment modalities target late stages of diabetic retinopathy (DR) when retinopathy has already been established. Novel and more sensitive strategies are needed. Optical coherence tomography angiography (OCTA) permits non-invasive visualisation of retinal microcirculation. Fibroblast growth factor-21 (FGF21) plays an important role in glucose and lipid homoeostasis. This study assesses early OCTA changes among children and adolescents with type 1 diabetes (T1DM) compared to fundus photography and correlates them to diabetes-duration, glycaemic control, and FGF21; hence, it determines their value in early detection of DR. METHODOLOGY: Hundred children and adolescents with T1DM were assessed for diabetes-duration, insulin therapy, hypoglycemia, and diabetic-ketoacidosis frequency, Tanner staging, glycated-haemoglobin (HbA1c), fasting lipids, urinary albumin/creatinine ratio, and serum FGF21. OCTA and fundus photography were done for the studied patients and 100 age, gender, and Tanner matched healthy controls. RESULTS: The mean age of the children and adolescents with T1DM was 10.84 years, their mean diabetes-duration was 3.27 years and their median FGF21 was 150 pg/ml. FGF21 was significantly higher among children and adolescents with T1DM than controls (p < 0.001). Children and adolescents with T1DM had a significantly larger foveal avascular zone (FAZ) and lower peripapillary and inside-disc capillary densities (p < 0.05); with no significant fundus photography difference (p = 0.155) than controls. FAZ was positively correlated and peripapillary and inside-disc capillary densities were negatively correlated with diabetes-duration, HbA1c, FGF21, and Tanner stage. FGF21 was significantly higher in T1DM children and adolescents having OCTA changes compared to those with normal OCTA (p = 0.002). Multivariate-regression revealed that FAZ is independently associated with diabetes-duration, HbA1c and FGF21. CONCLUSIONS: OCTA changes start early in children and adolescents with T1DM long before the fundus changes. These changes are correlated with diabetes-duration, puberty, glycaemic, and FGF21.

Metabolism and memory: α-synuclein level in children with obesity and children with type 1 diabetes; relation to glucotoxicity, lipotoxicity and executive functions.

BACKGROUND/OBJECTIVES: Children with obesity and those with type 1diabetes (T1D) exhibit subtle neurocognitive deficits, the mechanism of which remains unknown. α-synuclein plays a fundamental role in neurodegeneration. Moreover, its role in glucose and lipids metabolism is emerging. This study aims to assess whether α-synuclein is correlated with the degree of neurodegeneration in children with obesity and those with T1D in comparison to healthy controls and correlate it to various neurocognitive and metabolic parameters. SUBJECTS/METHODS: Forty children with obesity, 40 children with T1D and 40 matched-healthy controls were assessed for anthropometric measurements and blood-pressure. Cognitive evaluation was performed using Stanford-Binet scale and Barkley Deficits in Executive Functioning (EF) Scale-Children and Adolescents. α-synuclein, fasting lipids and glucose were measured with calculation of the homeostatic model of insulin-resistance and estimated-glucose disposal rate. RESULTS: Children with obesity and those with T1D had significantly higher α-synuclein (p < 0.001) and total EF percentile (p = 0.001) than controls. α-synuclein was negatively correlated to total IQ (p < 0.001 and p = 0.001), and positively correlated with total EF percentile (p = 0.009 and p = 0.001) and EF symptom count percentile (p = 0.005 and p < 0.001) in children with T1D and obesity, respectively. Multivariate-regression revealed that α-synuclein was independently related to age (p = 0.028), diabetes-duration (p = 0.006), HbA1C% (p = 0.034), total IQ (p = 0.013) and EF symptom count percentile (p = 0.003) among children with T1D, and to diastolic blood-pressure percentile (p = 0.013), waist/hip ratio SDS (p = 0.007), total EF percentile (P = 0.033) and EF symptom count percentile (p < 0.001) in children with obesity. CONCLUSION: α-synuclein could have a mechanistic role in neurocognitive deficit among children with obesity and T1D.

Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications.

Background: Growing evidences highlight the role of the innate immune response in the pathogenesis of type 1 diabetes (T1D) vascular complications. Neutrophil lymphocytic ratio (NLR) and platelet lymphocytic ratio (PLR) are inexpensive but novel markers of chronic inflammation might have prognostic value in children with T1D. Aim: To study NLR and PLR levels in children with T1D in comparison to matched controls and correlate them with fraction-C of glycosylated hemoglobin (HbA1C) and micro-vascular complications. Methodology: Hundred children with T1D were compared to 100 matched healthy controls. History included diabetes duration, insulin dose and frequency of hypoglycemic attacks. Fundus examination and the simple rapid neuropathy disability score were done. HbA1C, fasting lipids, urinary albumin excretion and complete blood count were measured with assessment of NLR and PLR. Results: NLR was significantly higher (p = 0.008) and PLR was significantly lower (p = 0.007) in children with T1D than controls. NLR was positively correlated while PLR was negatively correlated with HbA1C, diabetes duration, fasting cholesterol, triglycerides and LDL. NLR was significantly higher (p < 0.001) and PLR was significantly lower (p = 0.005) in children with microvascular complications than those without. Moreover, multivariate logistic regression revealed that microvascular complications were independently associated with NLR (p = 0.013) and PLR (p = 0.004). Conclusion: Children with T1D had significantly higher NLR and lower PLR compared to controls. These changes were more evident in those with diabetic microvascular complications than those without. Furthermore, NLR was positively correlated and PLR was negatively correlated to HbA1C, diabetes duration and hyperlipidemia. Hence, NLR and PLR can be a potential indicator for the risk of development of diabetic microvascular complications in children with T1D.

Psychosocial aspects of continuous subcutaneous insulin infusion in children with type 1 diabetes in Egypt; a limited resources country perspective.

BACKGROUND: Novel innovations continue to emerge in type-1 diabetes (T1D) management aiming to improve glycemic control. Assessing the psychosocial outcomes of different treatment modalities is specifically crucial among children with T1D and differs from one population to another. OBJECTIVES: To compare the health related quality of life (HRQoL) and confidence in diabetes self-management (CIDS) among children with T1D on continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) and to correlate them with the efficacy of glycemic control, Mini-International Neuropsychiatric Interview for Children and Adolescents(MINI-KID) depression module and socioeconomic-standard scale. METHODS: This real life study (ClinicalTrials.gov number NCT04756011) included 60 children with T1D (30 on CSII and 30 on MDI), aged 6-18 years. Disease duration, insulin therapy, average self-monitoring of blood glucose (SMBG) and HbA1C were assessed. CIDS, socioeconomic-standard, MINI-KID depression and HRQoL scales were applied. RESULTS: Children with T1D on CSII have significantly higher HRQoL and CIDS than those on MDI (P < 0.001). A significant negative correlation is found between HRQoL and insulin daily dose(P = 0.022), HbA1C(P < 0.001), average SMBG(P < 0.001) and MINI-KID depression scale(P < 0.001). A significant positive correlation is found between HRQoL and CIDS(P < 0.001) and health care, home sanitation, family possessions and occupation socioeconomic scores(P = 0.033, P = 0.001, P < 0.001 and P = 0.006, respectively). Multivariate regression analysis revealed that HRQoL is most associated with MINI-KID depression scale (P = 0.004) and annual total cost(P < 0.001). CONCLUSION: Children with T1D on CSII have significantly better HRQoL, CIDS and HbA1C with less depression than those on MDI.

Nail fold microangiopathy in adolescents with type 1 diabetes: Relation to diabetic vascular complications.

OBJECTIVES: Microangiopathy is implicated in the pathogenesis of diabetic vascular complications. Nail fold videocapillaroscopy (NVC) is an easy non-invasive tool of microvasculature assessment. This study compares the NVC changes in adolescents with Type1 diabetes (T1D) to healthy controls and correlates them to diabetic vascular complications. METHODS: Hundred thirty-five adolescents with T1D (disease duration 5 years) were compared to 135 matched controls. Diabetes duration, insulin therapy, fundus, and Toronto clinical scoring system (TCSS) were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin (HbA1C), urinary albumin creatinine ratio (UACR), nerve conduction velocity, and NVC were performed. RESULTS: NVC changes were found in 120 adolescents with T1D (88.8%). These changes were significantly higher in adolescents with T1D than controls (p < .001). Significant positive relation was found between NVC changes and TCSS (p = .006), diabetes duration (p = .001), HbA1C (0.008), cholesterol (p = .011), LDL (0.016), UACR (p < .001), and nerve conduction velocity (p < .001). Multivariate logistic regression study revealed that diabetic nephropathy and neuropathy were independently associated with NVC changes (p < .001 and p = .007, respectively). CONCLUSION: Adolescents with T1D have significantly higher NVC changes than controls. These changes were more evident in those having vascular complications than those without. Thus, NVC can be a potential non-invasive tool for early assessment and follow-up of the microvasculature among adolescents with T1D.

Pancreatic shear wave elastography in children with type 1 diabetes: relation to diabetes duration, glycemic indices, fasting C-peptide and diabetic complications.

BACKGROUND: Little is known about changes in the pancreas as the course of type 1 diabetes progresses. Recently, shear wave elastography (SWE) emerged as a tool for assessing pancreatic stiffness in chronic pancreatitis and pancreatic cancer with a few studies assessing it in diabetes. OBJECTIVE: To compare pancreatic SWE in children with recent-onset and long-standing type 1 diabetes to healthy controls and to correlate it with diabetes duration, glycated hemoglobin (HbA1C), functional B cell reserve (fasting C-peptide) and diabetic complications. MATERIALS AND METHODS: Fifty children with type 1 diabetes (25 with recent-onset and 25 with long-standing type 1 diabetes) and 50 controls were enrolled. Diabetes duration, insulin therapy, fundoscopic examination of the eyes and the neuropathy disability score were assessed. Fasting C-peptide, lipids, HbA1C and urinary albumin-creatinine ratio were measured. Pancreatic SWE was measured using the General Electric Logiq P9 ultrasound system. RESULTS: The mean SWE of the studied children with recent-onset type 1 diabetes was 4.81±0.62 kilopascals (Kpa), those with long-standing type 1 diabetes was 7.10±1.56Kpa and for controls was 5.57±0.27 Kpa (P<0.001). SWE was positively correlated to diabetes duration (P<0.001) and negatively correlated to fasting C-peptide (P<0.001). Regarding diabetes complications, SWE was positively correlated to frequency of severe hypoglycemia (P=0.005), HbA1C (P=0.03), low-density lipoproteins (P<0.001) and cholesterol (P<0.001) and significantly related to diabetic neuropathy (P=0.04) and nephropathy (P=0.05). Diabetes duration, fasting C-peptide, HbA1C and frequency of severe hypoglycemia were the significant independent variables related to SWE increase by multivariable regression analysis. CONCLUSION: Pancreatic SWE changes significantly with duration of type 1 diabetes, being lowest in those with recent-onset type 1 diabetes and highest in those with long-standing type 1 diabetes, particularly those with diabetic nephropathy and neuropathy.

Disordered eating behaviour in adolescents with type 1 diabetes on continuous subcutaneous insulin infusion; relation to body image, depression and glycemic control.

BACKGROUND: Disordered eating behaviour (DEB) represents a significant morbidity among people with type-1 diabetes (T1D). Continuous-subcutaneous insulin infusion (CSII) improves glycemic control and psychological wellbeing in those with T1D. However, its relation to DEB remains obscure. OBJECTIVES: To compare DEB among adolescents with T1D on CSII versus basal-bolus regimen and correlate it with body image, HbA1C and depression. METHODS: Sixty adolescents with T1D (30 on CSII and 30 on basal-bolus regimen), aged 12-17 years were studied focusing on diabetes-duration, insulin therapy, exercise, socioeconomic standard, hypoglycemic attacks/week and family history of psychiatric illness. Anthropometric measures, HbA1C, binge eating scale (BES), body image tool, patient health questionnaire-9 (PHQ9) and the Mini-KID depression scale were assessed. RESULTS: Among the studied adolescents with T1D, six had DEB (10%), 14 had poor body-image perception (23.3%), 42 had moderate body-image perception (70%) and 22 had depression (36.7%). Adolescents with T1D on CSII had significantly lower BES (p = 0.022), Mini-KID depression (p = 0.001) and PHQ9 (p = 0.02) than those on basal-bolus regimen. BES was positively correlated to depression (p < 0.001), HbA1C (p = 0.013) and diabetes-duration (p = 0.009) and negatively correlated to body-image (p = 0.003). CONCLUSION: DEB is a prevalent comorbidity among adolescents with T1D, with higher frequency in those on basal-bolus regimen than CSII.

Disordered eating behaviour is a significant morbidity among people with type 1 diabetes. It is associated with poor metabolic control and diabetes related complications even when the full diagnostic criteria of an eating disorder are not met. There is conflicting data in the literature regarding the prevalence of disordered eating behaviour in type 1 diabetes. The current study found that disordered eating behaviour is prevalent among 10% of the studied adolescents with type 1 diabetes. It was found to be more severe and frequent among those on basal-bolus insulin regimen than those on continuous subcutaneous insulin infusion. Moreover, it was correlated with depression, poor glycemic control, poor body image and long diabetes duration. Thus further studies are needed to verify the role of continuous glucose monitoring in the management of DEB among those with T1D.

Abdominal lymphadenopathy in children with Gaucher disease: Relation to disease severity and glucosylsphingosine.

Few case reports and series reported abdominal lymphadenopathy (ALN) in people with Gaucher disease (GD). However, it's prevalence among Gaucher population, clinical implications and potential biomarkers are unknown. Hence this study aims to assess the prevalence of ALN among children with GD & to correlate it to neutrophil-lymphocytic-ratio (NLR), platelet-lymphocytic-ratio (PLR) and glucosylsphingosine (Lyso-GL1). Fifty children with GD (14 type-1 and 36 type-3) on enzyme-replacement therapy (ERT) were compared to 50 matched healthy controls, focusing on history of pressure manifestations by ALN (diarrhea, constipation, abdominal pain, intestinal obstruction), and history of splenectomy, with calculation of severity scoring index (SSI). NLR, PLR and Lyso-GL1 were measured. Abdominal-ultrasound was done with assessment of liver and spleen volumes and ALN. CT-scan was done for those having significant lymphadenopathy. Twenty-six children with GD had ALN (52%). The most common presentations were abdominal-pain (22%) & constipation (18%), with intestinal-obstruction in 3 children (6%). Children with GD had significantly higher NLR (p < .001) and decreased PLR (p = .024) compared to controls. Interestingly, children with GD having ALN had significantly higher SSI (.012), Lyso-GL1 (p = .002) and NLR (p = .001) than those without ALN. Multivariate-logistic regression showed that ALN was independently related to Lyso-GL1 (p = .027), NLR (p = .023) and SSI (p = .032). Thus, ALN is a prevalent GD morbidity with wide clinical-spectrum ranging from asymptomatic cases to intestinal obstruction. ALN is related to SSI, NLR and Lyso-GL1 in children with GD.HighlightsChildren with GD had significantly higher NLR and lower PLR compared to controls.Children with GD having ALN had significantly higher SSI, Lyso-GL1 and NLR than those without ALN.ALN was independently related to Lyso-GL1, NLR and SSI in children with GD.

Ganglion Cell Complex Thinning in Young Gaucher Patients: Relation to Prodromal Parkinsonian Markers.

BACKGROUND: Patients with Gaucher disease (GD) have an increased risk for parkinsonism. Retinal thinning has been described in parkinsonism as an early nonmotor feature. Scarce reports have addressed retinal thickness changes in GD. OBJECTIVES: The objectives of this study were to compare ganglion cell complex (GCC) thickness in adolescents and young adults (AYAs) with GD with healthy control subjects, and to correlate it with the presence of parkinsonian features (PFs), clinical prodromal markers of parkinsonism, severity score index (SSI), and glucosylsphingosine (Lyso-GL-1). METHODS: This study included 48 AYAs with GD (11-29 years), 11 with manifest PFs (Group 1) and 37 with no PFs (Group 2), and 48 matched healthy control subjects (Group 3). Age of GD onset, disease duration, medication history, history of constipation, SSI, and hematological assessment were done. Neurocognitive evaluation included Parts I, II, and III of the Unified Parkinson's Disease Rating Scale (UPDRS), Wechsler Adult and Intelligence Scale and Wechsler Intelligence Scale for Children, Beck Depression Inventory (BDI), rapid eye movement sleep behavior disorder (RBD) scale, Munich Parasomnia Screening scale, and the olfactory dysfunction scale. Molecular analyses of the acid GBA gene and Lyso-GL-1 were done. Participants underwent full ophthalmological examination and optical coherence tomography with GCC thickness measurement. RESULTS: GCC was significantly thinner in Group 1 than in Groups 2 and 3 (P < 0.001), whereas no significant difference was found between Groups 2 and 3 (P = 0.977). In addition, a significant interocular GCC thickness difference was found among the studied AYAs with GD (P = 0.007). GCC correlated positively with total intelligence quotient (P < 0.001) and negatively with Lyso-GL-1 (P = 0.019), UPDRS (P = 0.004), and BDI (P = 0.029), but not with SSI (P = 0.874), GD type (P = 0.85), or genotype (P = 0.842). A significant negative relationship was found between GCC thickness and PFs (P = 0.001), parasomnia (P = 0.003), constipation (P = 0.031), RBD (P = 0.044), and hyposmia (P = 0.033). CONCLUSIONS: GCC thinning may be a promising biomarker for central nervous system neurodegeneration that has the potential to monitor early PFs among people with GD. © 2020 International Parkinson and Movement Disorder Society.

Vascular endothelial growth factor (VEGF), tissue inhibitors of metalloproteinase-1 (TIMP-1) and nail fold capillaroscopy changes in children and adolescents with Gaucher disease; relation to residual disease severity.

BACKGROUND: Gaucher disease (GD) is caused by functional defects of the acid ß-glucocerebrosidase enzyme, with accumulation of glucosylceramide in the macrophage lineage lysosomes causing multisystem abnormalities. However, some GD manifestations can't be explained by Gaucher-cells infiltration. Recent studies emphasized the role of inflammation in GD. AIM: To compare the level of TIMP1 (Tissue-inhibitory metalloproteinase-1) and VEGF (Vascular-endothelial growth factor) and nail-fold capillaroscopy (NFC) changes in children and adolescents (CA) with GD and controls and correlate them to disease-severity, genotype, visceral and neurological manifestations. METHODOLOGY: Fifty-three CA with GD were compared to 52 age and sex matched healthy controls stressing on ERT (enzyme replacement therapy) dose and duration, pulmonary, hematological and neurological manifestations with assessment of severity-scoring index (SSI). Full neurological, abdominal and chest examinations were done. Sonographic liver and spleen volumes and NFC were assessed. GD genotype was done. Serum TIMP-1 and VEGF were measured. RESULTS: CA with GD had significantly higher TIMP-1 (P < 0.001) and VEGF (P < 0.001) than controls. Type 3CA with GD had significantly higher TIMP-1 (P = 0.004) and VEGF (P = 0.035) than type 1. There was a significant positive correlation between TIMP-1 and each of VEGF (P < 0.001), SSI (P < 0.001) and NFC (P < 0.001). A significant positive relation was found between TIMP-1 and convulsions (P = 0.002), dysphagia (P = 0.008), opthalmoplegia (P = 0.038) and developmental delay (P < 0.001). Multi-variate logistic regression analysis for predictors of children and adolescents with GD revealed that its most correlated to TIMP-1 (P = 0.008) and NFC changes (P = 0.025). CONCLUSION: Macrophage proliferation in GD modulates local inflammation, micro-angiopathy and neo-angiogenesis. NFC can be used as a noninvasive indicator of microangiopathy in GD.

Cognitive decline and depressive symptoms: early non-motor presentations of parkinsonism among Egyptian Gaucher patients.

Evidence about the link between glucocerebrosidase (GCase) and parkinsonism is growing. Parkinsonism was described in adult type 1 Gaucher disease (GD); few case reports described it in type 3GD. To assess the presence of parkinsonian features in a cohort of Egyptian GD patients and correlate these findings to their genotype, phenotype, severity scoring index (SSI), cognitive function, and the presence of depressive symptoms. Twenty-four GD patients from the Pediatric Hematology Clinic, Ain Shams University, were assessed for medication history, neurological symptoms, depressive symptoms, and family history of parkinsonism. Anthropometric measures, complete neurological assessment, and SSI were examined. Neuropsychiatric evaluation included parts I, II, III, and V of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Wechsler Intelligence Scale for Children (WISC-children). Molecular analysis of the acid GBA gene was performed, and SSI was calculated. Sixteen GD patients (66.6%) had parkinsonian features with a male to female ratio of 1:1. Their mean age was 15.69 ± 5.62 (range, 12-26). They were all on enzyme replacement therapy (ERT) with a dose of 60 U/kg/2 weeks. Twelve GD patients were phenotypically type 3 (75%). Thirteen GD patients with parkinsonian features (81.25%) had L483P mutation. GD patients with parkinsonian features had higher SSI (P < 0.001), lower cognitive functions (P = 0.007), and more significant depressive symptoms (P = 0.031). Logistic regression analysis revealed that GD genotype (P = 0.003), GD type (P = 0.006), and cognitive functions (P = 0.03) were the only significant independent factors for the development of parkinsonian features among GD patients. With the increased life span and improved somatic manifestations of type 3GD on ERT, these patients can live to develop parkinsonism. Cognitive decline and depression can be early predictors of parkinsonism among GD population.

Regulatory T cells with CD62L or TNFR2 expression in young type 1 diabetic patients: relation to inflammation, glycemic control and micro-vascular complications.

BACKGROUND: Alteration of regulatory T cells (Tregs) may contribute to ineffective suppression of proinflammatory cytokines in type 1 diabetes. AIM: We determined the percentage of Tregs expressing CD62L or tumor necrosis factor receptor type 2 (TNFR2) in 70 young type 1 diabetic patients compared with 30 controls and assessed their relation to inflammation, glycemic control and micro-vascular complications. METHODS: High-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were assessed with flow cytometric analysis of Tregs, Tregs expressing CD62L or TNFR2. RESULTS: The percentage of CD4(+)CD25(high) T cells and CD4(+)CD25(high)CD62L(high) cells were significantly decreased while CD4(+)CD25(high)TNFR2(+) T cells were elevated in patients with micro-vascular complications than those without and controls (p<0.001). ROC curve revealed that the cutoff values of Tregs, Tregs expressing CD62L and Tregs expressing TNFR2 (7.46%, 24.2% and 91.9%, respectively) could detect micro-vascular complications. Significant negative correlations were observed between Tregs expressing CD62L and disease duration, FBG, HbA1c, urinary albumin excretion and hs-CRP, whereas, positive correlations were found between Tregs expressing TNFR2 and these variables (p<0.05). TNF-α was significantly increased while IL-10 was decreased among patients with micro-vascular complications than those without (p<0.05). CONCLUSIONS: Alteration in the frequency of Tregs and Tregs expressing CD62L or TNFR2 in type 1 diabetes is associated with increased inflammation, poor glycemic control and risk of micro-vascular complications.