Fasting Ramadan in patients with T1DM - Saudi Arabia versus other countries during the COVID-19 pandemic.

BACKGROUND AND AIMS: To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic. METHODS: Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020. RESULTS: 1485 Type1 diabetes (T1DM) patients analyzed; 705 (47.5%) from Saudi Arabia vs. 780 (52.5%) from other countries. 1056 (71.1%) fasted Ramadan; 636 (90.2%) of Saudi patients vs. 420 (53.8%) of other countries. Experiencing Ramadan during the COVID-19 pandemic did not affect the Saudi T1DM patients' decision to fast while it significantly influenced their decision in other countries (1.4 vs 9.9%, P < 0.001). More Saudi patients needed to break the fast due to a diabetes related complication compared to other countries (67.4% vs. 46.8%, p=<0.001). The mean number of days fasted in Saudi and other countries was 24 ± 7 and 23 ± 8 days respectively. Hypoglycemic events were more common among Saudi patients during Ramadan compared to other countries 72% and 43.6% (p < 0.001) respectively. There was a significant difference in timing; the largest peak for Saudi Arabia patients was after dawn (35% vs 7%, p < 0.001), while it was pre-sunset for the other countries (23 vs 54%, p = 0.595). Day time-hyperglycemia was also more common among Saudi patients (48.6% vs. 39%, p < 0.001), however it was a less likely cause to break the fast (25.6% vs 38.3%, p < 0.001). CONCLUSION: Observing the fast of Ramadan is extremely common among Saudi T1DM patients compared to other Muslim countries and was not affected by the COVID-19 pandemic. However, it was associated with higher frequency of hypoglycemic and hyperglycemic episodes.

Transient elastography as a noninvasive assessment tool for hepatopathies of different etiology in pediatric type 1 diabetes mellitus.

AIM: To identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. METHODS: One hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. RESULTS: Thirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1-11.8kPa); 24 were Metavir F0-F1, 7 were F2-F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. CONCLUSIONS: Hepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.

Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.

Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging.

The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with ß-thalassaemia major (ß-TM). A total of 50 adolescent patients with ß-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with ß-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=-0.376, p=0.014 and r=-0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

Plasma thrombin-activatable fibrinolysis inhibitor levels in children and adolescents with type 1 diabetes mellitus: possible relation to diabetic microvascular complications.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a potent inhibitor of fibrinolysis isolated from human plasma. This study was designed to investigate the association between TAFI levels in relation to metabolic control, microvascular complications and lipid profile in a cohort of Egyptian children and adolescents with type 1 diabetes mellitus (T1DM). Eighty normotensive nonobese type 1 diabetic patients (45 with and 35 without microvascular complications) with a mean age of 12.75 ± 3.6 years and mean disease duration of 7.42 ± 2.4 years in addition to 60 sex and age-matched normal individuals were enrolled in this study. Anthropometric measurements, blood pressure and microvascular complications were analysed. HbA1c, albumin-to-creatinine ratio in urine, lipid profile and TAFI levels were measured. Plasma level of TAFI in diabetic patients was significantly elevated, compared with normal individuals (16 ± 2.8 vs. 10.3 ± 0.7 µg/ml; P < 0.004). Plasma level of TAFI in diabetic patients with microvascular complications was significantly higher than in diabetic patients without complications (17.9 ± 1.8 vs. 12.9 ± 0.6 µg/ml; P < 0.001). Plasma TAFI levels were positively correlated with HbA1c levels (r = 0.38; P < 0.03) and SBP (r = 0.37; P < 0.02). Total cholesterol and triglycerides were higher in patients with microvascular complications than in those without complications (P < 0.001, P < 0.05, respectively). Our results showed that TAFI is considered a valid predictor for microvascular complications with best cut off value 15 µg/ml with sensitivity of 99% and specificity of 100%. Our data imply that increased plasma TAFI as well as high lipid levels may be involved in the mechanism of vascular endothelial damage in patients with T1DM. This suggests the possibility of TAFI participating in the mechanism of hypofibrinolysis, hence occurrence of microvascular complications in diabetes.

An Egyptian case of congenital hyperinsulinism of infancy due to a novel mutation in KCNJ11 encoding Kir6.2 and response to octreotide.

Congenital hyperinsulinism of infancy (CHI) is a rare heterogeneous disease mostly attributable to mutations in the genes encoding the KATP channel subunits found in pancreatic ß-cells. Here, we report a child presenting at day 1 with persistent hyperinsulinemic hypoglycemia and who underwent open laparotomy and subtotal pancreatectomy with resection of tail and body of pancreas at 30 days of age. Normoglycemia was restored by Octreotide that was discontinued when the child was 7-month old. However, 3 months later Octreotide was re-administered as hypoglycemic attacks recurred. On follow-up, the child has adequate glycemic control and is thriving well with no neurodevelopmental morbidity. Genetic analysis revealed the novel mutation c.407G > A [p.R136H] in KCNJ11 encoding Kir6.2, confirming the diffuse form of CHI. This is to our knowledge the first reported Egyptian case of CHI due to a mutation in KCNJ11.

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.

Risk of bleeding and inhibitor development after circumcision of previously untreated or minimally treated severe hemophilia A children.

BACKGROUND: Surgery and intensive factor VIII (FVIII) replacement may be risk factors for development of inhibitors. OBJECTIVE: To evaluate time and rate of inhibitor development postcircumcision over 12-month period, and to assess bleeding of children with severe hemophilia A after low-dose FVIII replacement and local hemostasis. PATIENTS AND METHODS: Sixty-one previously untreated patients (PUPs) or minimally treated patients (MTPs) with severe hemophilia A less than 36 months were enrolled; 25 underwent circumcision during the 18-month enrollment period, and 36 matched patients were not circumcised. All patients were treated on demand with plasma-derived FVIII, and all were inhibitor negative at the time of enrollment. Intron 22 inversion was analyzed. A potent hemostatic agent (gelatin sponge) was applied on the site of surgery, and then dressed with gauze. Two doses of FVIII concentrate (25 U/kg) were given, 1 hour before circumcision and 1 hour before removal of dressing. The inhibitor was determined every 8 exposure days (EDs). RESULTS: None of the patients had bleeding or infection, except one who had minimal transient bleeding 8 days after surgery, and was treated easily by a single dose of FVIII (50 U/kg). After a median of 16 EDs, high-titer inhibitors developed in seven patients: three patients in the circumcised group (12%) in contrast to four patients (11.1%) in the noncircumcised group. CONCLUSION: Two doses factor concentrate and gelatin sponge application were generally enough to prevent bleeding after circumcision of severe hemophilia A. Circumcision and low-dose FVIII protocol were not an additional risk for development of high-titer inhibitor.

Cochleopathy in Egyptian adolescents with Type 1 diabetes mellitus.

BACKGROUND: Diabetic neuropathy is recognized as the most common clinical picture of nervous system disorders caused by diabetes mellitus (DM). Although peripheral and autonomic nervous system involvements are frequently encountered, data about the incidence of central diabetic neuropathies is limited. OBJECTIVE: Our study aimed to detect early asymptomatic auditory impairment whether at the level of outer hair cells (OHCs), inner hair cells (IHCs) and or olivo-cochlear bundle and the relationship between these abnormalities and other variables such as diabetes duration, degree of the metabolic control, or presence of microvascular complications. SUBJECTS AND METHODS: Seventy five adolescents with Type 1 DM and thirty three healthy controls participated in the study. Duration of DM, glycated hemoglobin (HbA1c) levels, microvascular complications were analyzed. All underwent basic audiological assessment to ensure normal hearing and normal middle ear function. Other tests comprised: transiently evoked otoacoustic emissions (TEOAEs) testing OHCs, TEOAEs with contralateral suppression (testing the integrity of olivo-cochlear bundle) and threshold equalizing noise (TEN) testing IHCs as evidenced by dead regions within the cochlea. RESULTS: Early asymptomatic OHCs involvement as reflected by partial pass in 33.3% of cases with diminished suppression as compared to 9.1% control group. Eleven patients (7.33%) showed positive TEN Test reflecting resistance of IHCs to hyperglycemic injury. Diabetic patients had significantly higher amplitude on TEOAEs with noise suppression when compared to controls (P=0.002). The mean difference in amplitude of TEOAEs before and after suppression was significantly higher in diabetics with microvascular complications when compared to diabetic children without complications at all frequencies (P<0.001 for all). Duration of diabetes and microvascular complications (nephropathy, peripheral and autonomic neuropathy) were not correlated with the lack of suppression except for retinopathy (P=0.02). In contrast, poor metabolic control was associated with poor suppression (r=-0.443, P=0.001). CONCLUSIONS: Cochleopathy can be detected in a relatively high proportion of subjects with Type 1 diabetes in spite of a normal audiometric hearing threshold. It should be considered as early manifestation of diabetic neuropathy which is related to the degree of metabolic control and retinopathy independent of other microvascular complications.

Insulin-like growth factor-1 cytokines cross-talk in type 1 diabetes mellitus: relationship to microvascular complications and bone mineral density.

OBJECTIVE: This study was designed to investigate the association between inflammatory cytokines (IL-8, IL-6) and IGF-1 levels in relation to metabolic control, microvascular complications and bone mineral density (BMD) in a cohort of Egyptian adolescents with T1DM. RESEARCH DESIGN AND METHODS: Sixty patients with T1DM (mean age was 14.67±1.53 years, mean disease duration was 6.87±1.25 years) and 40 controls participated in the study. Thirty-six patients (60%) had poor glycemic control (HbA1C measurements ≥8%) while the rest (n=24%, 40%) had good glycemic control (HbA1C measurements <8%). Serum IL-6, IL-8, and IGF-1 levels were measured. Whole body DXA scan were assessed. Total body and lumbar spine (L2-L4) bone mineral content (BMC, g) and bone area (BA, cm(2)) were measured by DXA scan, bone mineral density (BMD, g/cm(2)) was calculated by BMC/BA. RESULTS: Patients with T1DM had higher IL-6 and IL-8 levels with lower IGF-1 than healthy controls (P<0.001). Within the T1DM patients those with poor glycemic control had higher IL-6 and IL-8 as well as lower IGF-1 and total BMD than those with good glycemic control (P<0.001 for all). IL-6 and IL-8 were negatively correlated with IGF-1 (P=0.005 and 0.021, respectively). The peripheral neuropathy rate was also greater in T1DM patients with poor glycemic control (P=0.02). Presence of nephropathy or retinopathy was not different (P=0.69 and 0.50, respectively). CONCLUSION: High IL-6, IL-8 with low IGF-1 levels are found in adolescents with T1DM. It seems that poor glycemic control exacerbates inflammatory cytokines, increases peripheral neuropathy, and decreases bone mineral density.

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

BACKGROUND: Type 1 diabetes mellitus (T1DM) is associated with a high risk for early atherosclerotic complications especially risk of coronary heart disease. OBJECTIVE: To 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 METHODS: A 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. RESULTS: Exercise 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). CONCLUSION: Exercise is an indispensable component in the medical treatment of patients with T1DM as it improves glycemic control and decreases cardiovascular risk factors among them.