Mona Salem

Microvascular and macrovascular complications in children and adolescents

Kim C Donaghuea,b, R Paul Wadwac, Linda A Dimegliod, Tien Y Wonge, Francesco Chiarellif, M Loredana Marcovecchiof, Mona Salemg, Jamal Razah, Paul L Hofmani and Maria E Craiga,b,j aInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, Australia; bDiscipline of Paediatrics and Child Health, University of Sydney, Sydney, Australia; cBarbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Denver, CO, USA; dPediatric Endocrinology and Diabetology, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA; eSingapore National Eye Centre, Singapore Eye Research Institute, Singapore, Singapore; fDepartment of Paediatrics, University of Chieti, Chieti, Italy; gDepartment of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt; hNational Institute of Child Health, Karachi, Pakistan; iLiggins Institute, University of Auckland, Auckland, New Zealand and jSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia

Is exercise a therapeutic tool for improvement of cardiovascular risk factors in adolescents with type 1 diabetes mellitus? A randomised controlled trial

BackgroundType 1 diabetes mellitus (T1DM) is associated with a high risk for early atherosclerotic complications especially risk of coronary heart disease.ObjectiveTo evaluate the impact of six months exercise prgram on glycemic control, plasma lipids values, blood pressure, severity and frequency of hypoglycemia, anthropometric measurements and insulin dose in a sample of adolescents with T1DM.Research design and methodsA total of 196 type 1 diabetic patients participated in the study. They were classified into three groups: Group (A) did not join the exercise program(n = 48), group (B) attended the exercise sessions once/week (n = 75), group (C) attended the exercise sessions three times/week (n = 73). Studied parameters were evaluated before and six months after exercise programe.ResultsExercise improved glycemic control by reducing HbA1c values in exercise groups (P = 0.03, P = 0.01 respectively) and no change in those who were not physically active (P = 0.2). Higher levels of HbA1c were associated with higher levels of cholesterol, LDL-c, and triglycerides (P = 0.000 each). In both groups, B and C, frequent exercise improved dyslipidemia and reduced insulin requirements significantly (P = 0.00 both), as well as a reduction in BMI (P = 0.05, P = 0.00 respectively) and waist circumference(P = 0.02, P = 0.00 respectively). The frequency of hypoglycemic attacks were not statistically different between the control group and both intervention groups (4.7 ± 3.56 and 4.82 ± 4.23, P = 0.888 respectively). Reduction of blood pressure was statistically insignificant apart from the diastolic blood presure in group C (P = 0.04).ConclusionExercise is an indispensable component in the medical treatment of patients with T1DM as it improves glycemic control and decreases cardiovascular risk factors among them.

Urinary excretion of n-acetyl-beta-D-glucosaminidase and retinol binding protein as alternative indicators of nephropathy in patients with type 1 diabetes mellitus.

Abstract: Diabetic nephropathy (DN) is usually characterized by glomerular dysfunction, with microalbuminuria as an early indicator. Urinary excretion of smaller molecular weight proteins such as n‐acetyl‐β‐glucosaminidase (β‐NAG) and retinol binding protein (RBP) indicate proximal tubular dysfunction, and may identify diabetic patients at risk of developing diabetic nephropathy. In a trial to assess renal tubular function, urinary excretion of β‐NAG (by colorimetric assay) and RBP (by ELISA) were determined in 59 type 1 diabetic patients (mean age 15 ± 3.2 yr). Of the 59 patients, 11 were microalbuminuric while 48 had normal urinary albumin excretion (UAE). Patients were compared with 40 matched healthy subjects. Diabetic patients with microalbuminuria (n = 11) had concomitant renal tubular disorder indicated by high urinary β‐NAG in all (100%) and RBP in 10 (90.9%) of them. Meanwhile, patients without microalbuminuria (n = 48) had both tubular markers excreted in urine in significantly higher amounts than controls (mean β‐NAG = 6.88 vs. 3.76 U/g Cr, p < 0.001; RBP = 386.6 vs. 151.8 µg/dL, p < 0.001). Among those patients, 29 (61%) had raised urinary β‐NAG activity, and 39 (82%) had increased loss of RBP in urine. A significant correlation was found between urinary β‐NAG and RBP in normoalbuminuric patients (r = 0.66, p < 0.001), as well as between each of the two tubular markers and HbA1c (r = 0.83, p < 0.001). At 30 and 36 months of follow‐up, two out of 48 (4.2%) diabetic patients developed persistent microalbuminuria. Both had elevated baseline HbA1C, and urinary β‐NAG. In conclusion, proximal tubular dysfunction may occur independent of glomerular alteration. Whether tubular markers precede the development of microalbuminuria needs further study.

Breast-Feeding and Childhood-Onset Type 1 Diabetes: A pooled analysis of individual participant data from 43 observational studies

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I2 = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Early predictors of myocardial disease in children and adolescents with type 1 diabetes mellitus

Background: The spectrum of diabetic heart disease involves a progression from normal heart to preclinical left ventricular diastolic and systolic dysfunction followed by overt echocardiographic evidence of left ventricular (LV) dysfunction and finally symptomatic heart failure.

Single photon emission tomography (SPECT) study of regional cerebral blood flow in normoalbuminuric children and adolescents with type 1 diabetes.

Abstract: Cerebral damage in diabetes can be related to chronic hyperglycemia and recurrent severe hypoglycemia as well as due to the associated vasculopathy. The pattern of regional cerebral blood flow using cerebral single photon emission tomography (SPECT) was evaluated in normoalbuminuric type 1 diabetic children and adolescents and its relation to the metabolic control and cognitive functions. Thirty‐one type 1 diabetics aged 10–18 yr (mean 14.7 ± 3.4) were included, 16 males and 15 females, divided into four groups: group I (n = 8) with history of recurrent severe hypoglycemia (≥ 3); group II (n = 8) with history of severe diabetic ketoacidosis (≥ 3); group III (n = 7) with recurrent minor hypoglycemia 
(≥ 3/week); and group IV (n = 8) with controlled diabetes. The control group (V) comprised seven healthy children, aged 10–18 yr (mean 14.2 ± 3.1). SPECT was done using technetium‐99m hexamethyl propylene amine oxime. There was significant brain hypoperfusion in diabetics compared with controls, mainly in the basal ganglia (p < 0.01) and frontal regions (p < 0.01), with less changes in parietal and temporal regions. These changes were not related to the age, sex, diabetes duration, mean blood glucose or HbA1C. Basal ganglia hypoperfusion was significant in groups I (p < 0.01) and II (p < 0.01) compared with controlled diabetics. There was no correlation between cerebral SPECT changes and cognitive scores in type 1 diabetics.

Abnormal glucose tolerance in Egyptian beta‐thalassemic patients: possible association with genotyping

Abstract:  Background:  Type 1 diabetes mellitus (DM) is a frequent complication in patients with beta‐thalassemia. It is believed to be due to the damage inflicted by iron overload of the pancreatic beta cells. Liver disorders and genetic influences seem to be additional predisposing factors.

Platelets microparticles as a link between micro- and macro-angiopathy in young patients with type 1 diabetes

Abstract The development of vasculopathies in diabetes involves multifactorial processes. Increased levels of platelets-derived microparticles (PMPs) have been reported in diseases associated with thrombotic risk, but few data are available in diabetes. We explored the level of PMPs in young patients with type 1 diabetes in relation to inflammation, glycemic control, micro-vascular complications and carotid intima media thickness (CIMT). Eighty children and adolescents with type 1 diabetes were divided into two groups according to the presence of micro-vascular complications and compared with 40 healthy controls. Patients were subjected to medical history, clinical examination and assessment of high-sensitivity C-reactive protein (hs-CRP), HbA1c, urinary albumin creatinine ratio (UACR), flow cytometric analysis for PMPs using anti-CD41b and CIMT. PMP levels were significantly increased in all patients with type 1 diabetes (2.92 ± 1.3%) whether with micro-vascular complications (3.46 ± 1.11%) or those without complications (2.37 ± 1.28%) compared with healthy controls (1.28 ± 0.64%; p < 0.001). CIMT was significantly elevated in all patients, and the highest levels were among those with micro-vascular complications (p < 0.001). Significant positive correlations were found between PMPs and body mass index, HbA1c, serum creatinine, total cholesterol, UACR, hs-CRP and CIMT (p < 0.05). Multiple linear regression analysis showed that HbA1c, UACR, hs-CRP and CIMT were independently related to PMPs levels in type 1 diabetes. According to Receiver operating characteristic curve analysis, the cutoff value of PMPs at 2.48% could differentiate patients with and without micro-vascular complications with a sensitivity of 80% and specificity of 73.3%. PMPs are elevated in patients with type 1 diabetes and can be considered as an early marker of micro-vascular complications and subclinical atherosclerosis.

An Egyptian family with H syndrome due to a novel mutation in SLC29A3 illustrating overlapping features with pigmented hypertrichotic dermatosis with insulin-dependent diabetes and Faisalabad histiocytosis.

The SLC29A3 gene, encoding hENT3, a member of the equilibrative nucleoside transporter family, has recently been found mutated in Faisalabad histiocytosis, pigmented hypertrichotic dermatosis with insulin‐dependent diabetes, familial sinus histiocytosis with massive lymphadenopathy (SHML), and H syndromes. We here report clinical and genetic findings of an Egyptian family with H syndrome. We describe two siblings, a 19‐yr old girl and a 15‐yr old boy, of consanguineous parents. From 5 yr of age, the girl developed bilateral flexion deformity of interphalengeal joints and insulin‐dependent diabetes mellitus. At age 7 yr, prominent hyperpigmented patches appeared on the skin at lower limbs, genitalia, and trunk. On clinical examination, she had hepatosplenomegaly, generalized lymphadenopathy, left ventricular hypertrophy, sensorineural hearing loss, hypogonadism, short stature, and characteristic dysmorphic features. Her brother had fixed flexion contractures of the feet, profound sensorineural hearing loss, characteristic dysmorphic features, but no diabetes. DNA sequence analysis revealed a homozygous mutation (c.300+1G>C) in SLC29A3 in both siblings. The phenotype and genotype of the siblings were compatible with that of the H syndrome, although the features were overlapping with those found in pigmented hypertrichotic dermatosis with insulin‐dependent diabetes, familial SHML, and Faisalabad histiocytosis, indicating that these four syndromes may be regarded as one disease with varying phenotypic features. A new, common name for these conditions is warranted.

A prospective study of the hypothalamic-pituitary-adrenal axis in children with acute lymphoblastic leukemia receiving chemotherapy

Abstract Background Glucocorticoids are essential in protocols of therapy of acute lymphoblastic leukemia (ALL). Objectives To assess the incidence, severity, morbidity, and risk factors of hypothalamic-pituitary-adrenal axis (HPA) suppression in children with ALL, and the time course of recovery. Design Forty standard risk ALL children treated in the Pediatric Hematology/Oncology Unit, Ain-Shams University, Egypt, were classified into dexamethasone (DXM) group: 20 patients on children cancer group protocol and prednisone (PDN) group: 20 patients on modified Berlin-Frankfurt-Muenster (BFM) study group 90 protocol. Patients were followed clinically and by laboratory assessment of morning s.ACTH, basal and after low-dose adrenocorticotrophic hormone stimulation test of cortisol and DHEAS, at diagnosis and every 2 weeks till adrenal recovery. Results HPA recovery was earlier in PDN than DXM group (P < 0.05). In induction phases 1 and 2: 65 and 75% of PDN group recovered on week 2, while 45 and 50% of DXM group recovered in week 4. Adrenal recovery was predicted 2 weeks earlier by normalized s.DHEAS. Children below 5 years of age had earlier recovery in PDN group (P = 0.04), no age effect in DXM group. Conclusion Adrenal suppression is an inevitable consequence of ALL therapy. Monitoring of cortisol levels and steroid coverage during stress is recommended, and gradual steroid tapering is suggested.