Study of Insulin Attached onto Magnetic Nanoparticles

Glucose regulation is compromised in diabetic patients and hence diabetes is characterized by accumulation of glucose in blood. As a standard practice diabetic patients usually self-administer subcutaneous insulin injections daily, which are usually associated with pain, tissue necrosis, microbial contamination and nerve damage to local areas. Glucose-responsive implantable devices have provided a hope for a brighter future of diabetes management. However, one of the limitations of such devices is their refill requirement, which often requires surgical procedures leading to lower patient compliance. To overcome this limitation led to the idea of reusing insulin after it has been in the body circulation system and later becomes residues. To make this idea work, the first step proposed in this thesis is to tag insulin with magnetic nanoparticles and then to use a magnetic guidance system to bring it back the residue insulin to the implanted device before it can go to the clearance sites. Obviously, the precondition for the foregoing idea to work is to make sure that insulin’s conformation is not affected by the attachment with magnetic nanoparticles. This thesis was designed to study this precondition. The hypothesis is that the insulin’s conformation will not be affected by the attachment with the magnetic nanoparticles. Two specific objectives are: (1) assessment of the feasibility of potential capturing techniques and analysis of the attachment of insulin onto the magnetic nanoparticles to confirm the attachment; (2) measurement of the insulin’s conformation before and after it is attached with the magnetic nanoparticles. The spectroscopy techniques, including Fourier transform infrared, circular dichroism, absorbance and fluorescence spectroscopy, were used to conduct data collection and analysis. All four of these spectroscopies provide important information concerning the research objectives of this thesis. The results from the fluorescence and absorbance spectroscopy confirm the attachment of insulin onto the magnetic nanoparticles, hence the achievement of Objective 1. The results from the CD and FTIR spectroscopy show that insulin’s conformation is unchanged before and after its attachment onto magnetic nanoparticles, hence the achievement of Objective 2. The general conclusion of the study is that the insulin’s conformation will not be affected by the attachment of it with magnetic nanoparticles

Prevalence and risk factors for painful diabetic neuropathy in secondary health care in Qatar.

AIMS/INTRODUCTION:Painful diabetic peripheral neuropathy (PDPN) has a significant impact on the patient's quality of life. The prevalence of PDPN in the Middle East and North Africa (MENA) region has been reported to be almost double that of populations in the UK. We sought to determine the prevalence of PDPN and its associated factors in T2DM patients attending secondary care in Qatar. MATERIALS AND METHODS:This is a cross-sectional study of 1095 participants with T2DM attending Qatar's two national diabetes centers. PDPN and impaired vibration perception on the pulp of the large toes were assessed using the DN4 questionnaire with a cut-off ≥4 and the Neurothesiometer with a cut-off ≥15V, respectively. RESULTS:The prevalence of PDPN was 34.5% (95% CI: 31.7%-37.3%), but 80% of these patients had not previously been diagnosed or treated for this condition. Arabs had a higher prevalence of PDPN compared to South Asians (P<0.05). PDPN was associated with impaired vibration perception AOR=4.42 (95%CI: 2.92-6.70), smoking AOR=2.43 (95%CI: 1.43-4.15), obesity AOR=1.74 (95%CI: 1.13-2.66), being female AOR=1.65 (95%CI: 1.03-2.64) and duration of diabetes AOR=1.08 (95%CI: 1.05-1.11). Age, poor glycemic control, hypertension, physical activity and proteinuria showed no association with PDPN. CONCLUSIONS:PDPN occurs in 1/3 of T2DM patients attending secondary care in Qatar, but the majority have not been diagnosed. Arabs are at higher risk for PDPN. Impaired vibration perception, obesity and smoking are associated with PDPN in Qatar. This article is protected by copyright. All rights reserved

Prevalence and management of diabetic neuropathy in secondary care in Qatar

Aims Diabetic neuropathy (DN) is a “Cinderella” complication, particularly in the Middle East. A high prevalence of undiagnosed DN and those at risk of diabetic foot ulceration (DFU) is a major concern. We have determined the prevalence of DN and its risk factors, DFU and those at risk of (DFU) in patients with T2DM in secondary care in Qatar. Materials and methods Adults with T2DM were randomly selected from the two National Diabetes Centers in Qatar. DN was defined by the presence of neuropathic symptoms and a vibration perception threshold (VPT) ≥ 15 V. Participants with a VPT≥25 V were categorized as high risk for DFU. Painful DN was defined by a DN4 score ≥ 4. Logistic regression analysis was used to identify predictors of DN. Results In 1082 adults with T2DM (age 54 ± 11 years, duration of diabetes 10.0 ± 7.7 years, 60.6% males) the prevalence of DN was 23.0% (95% CI: 20.5%‐25.5%), of whom 33.7% (95% CI: 27.9%‐39.6%) were at high risk of DFU and 6.3% had DFU. 82.0% of the patients with DN were previously undiagnosed. The prevalence of DN increased with age and duration of diabetes and was associated with poor glycemic control (HbA1c ≥ 9%) AOR = 2.1 (95%CI: 1.3‐3.2), hyperlipidemia AOR = 2.7 (95%CI: 1.5‐5.0) and hypertension AOR = 2.0 (95%CI: 1.2‐3.4). Conclusions Despite, DN affecting 23% of adults with T2DM, 82% had not been previously diagnosed with 1/3 at high risk for DFU. This argues for annual screening and identification of patients with DN. Furthermore, we identify hyperglycemia, hyperlipidemia and hypertension as predictors of DN

Glucose‐lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes

Aim: Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN. Methods: Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL). They underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function and corneal confocal microscopy (CCM) at baseline and follow‐up between 4 and 7 years. Results: Of 76 participants, 69.7% were on glucose lowering medication associated with WG, and 30.3% were on glucose lowering medication associated with WL. At baseline, participants in the WG group had a significantly longer duration of diabetes (p < .01), higher douleur neuropathique en 4 (DN4) score (p < .0001) and VPT (p = .01) compared with those in the WL group. Over a 56‐month period, participants in the WG group showed no significant change in body weight (p = .11), HbA1c (p = .18), triglycerides (p = .42), DN4 (p = .11), VPT (p = .15) or Sudoscan (p = .43), but showed a decline in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) (p < .0001). Participants in the WL group showed a reduction in weight (p = .01) and triglycerides (p < .05), no change in DN4 (p = .30), VPT (p = .31) or Sudoscan (p = .17) and a decline in the corneal nerve branch density (p < .01). Conclusions: Participants treated with glucose lowering medication associated with weight gain had worse neuropathy and greater loss of corneal nerves during follow‐up, compared to patients treated with medication associated with weight loss

Prenatal Diagnosis of Third and Fourth Branchial Apparatus Anomalies: Case Series and Comparison with Lymphatic Malformation.

Background and purposeThird and fourth branchial apparatus anomalies are rare congenital anomalies. The purpose of this study was to investigate imaging features of these lesions on fetal MR imaging in comparison with lymphatic malformations, the major competing differential diagnosis in these cases.Materials and methodsA retrospective review of our institutional fetal MR imaging database between 1997 and 2019 resulted in 4 patients with confirmed third and fourth branchial apparatus anomalies and 14 patients with confirmed lymphatic malformations. The imaging features were reviewed by consensus, and the Fisher exact test was used to evaluate statistically significant differences between these 2 populations.ResultsFour cases of third and fourth branchial apparatus anomalies were imaged at 29 weeks 1 day (range, 23 weeks 1 day to 33 weeks 4 days). All 4 cases demonstrated unilateral, unilocular cysts without reduced diffusion or hemorrhage and a medially directed beaked contour that tapered between the spine and airway at the level of the piriform sinus. Compared with 14 cases of fetal lymphatic malformations imaged at 27 weeks 6 days (range, 21 weeks 3 days to 34 weeks 6 days), third and fourth branchial apparatus cysts were significantly more likely to be unilocular (P &lt; .005) and to have a medially beaked contour (P &lt; .005). The combination of features of unilateral, unilocular, and medially beaked contour was observed only in the fetuses with third and fourth branchial apparatus cysts (P &lt; .001).ConclusionsThe presence of a left-sided unilocular cyst with a medially beaked contour tapering at the level of the piriform sinus suggests the diagnosis of third and fourth branchial apparatus anomaly. Accurate diagnosis in the prenatal period allows proper counseling, genetic work-up, and treatment, potentially sparing patients from recurrent infections and associated morbidity

Evaluation of survival weighted Pareto distribution: Analytical properties and applications to industrial and aeronautics data

In statistical modeling, lifetime datasets play an important and significant role. Weighted distributions can be useful to attain the essential purposes relating to the developed distributions’ flexibility and to improve further compliances in data forming; they provide the extension of distributions. The current study suggests a new best-fit probability distribution model based on Pareto distribution. The new model is called Survival Weighted Pareto (SWP) distribution model. Furthermore, the statistical expressions for different properties, which include moments, inverse moments, quantile function, and order statistics, are reported. Moreover, to check the performance and the behavior of different estimators using different sample sizes, a simulation study, which is based on SWP distribution, is performed. According to the simulation results, it is established that the proposed model is a most useful fitted probability model. In addition, an application of the SWP model for three datasets is provided to check the goodness of fit measures of the model

Metformin Use Is Not Associated With B12 Deficiency or Neuropathy in Patients With Type 2 Diabetes Mellitus in Qatar

BackgroundMetformin may lead to B12 deficiency and neuropathy. There are no published data on the prevalence of Metformin-related B12 deficiency and neuropathy in the Arabian Gulf.AimsDetermine whether Metformin intake is associated with B12 deficiency and whether B12 deficiency is associated with diabetic peripheral neuropathy (DPN) and painful diabetic neuropathy.MethodsPatients with type 2 diabetes mellitus (T2DM) (n = 362) attending outpatient clinics at HMC underwent assessment of B12 levels, the DN4 questionnaire, and vibration perception threshold (VPT).ResultsComparing Metformin to non-Metformin users there were no differences in B12 levels, VPT, or DN4. The prevalence of B12 deficiency (B12 &lt;133 pmol/l) was lower (P &lt; 0.01) in Metformin (8%) compared to non-Metformin (19%) users. Patients with B12 deficiency had a comparable prevalence and severity of sensory neuropathy and painful neuropathy to patients without B12 deficiency.ConclusionSerum B12 levels were comparable between Metformin and non-Metformin users with T2DM in Qatar. T2DM patients on Metformin had a lower prevalence of B12 deficiency. Furthermore, the prevalence and severity of neuropathy and painful diabetic neuropathy were comparable between patients with and without B12 deficiency