Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency

In phenylalanine hydroxylase (PAH) deficiency, an easily feasible method to access the progression of neurodegeneration is warranted to contribute to current discussions on treatment indications and targets. The objective of the present study was to investigate whether optical coherence tomography (OCT) measures as markers of neurodegeneration differ between patients with PAH deficiency and healthy controls (HCs) according to phenotype and metabolic control. In this single-center cross-sectional study, 92 patients with different phenotypes of PAH deficiency [PAH deficiency not requiring treatment, early treated phenylketonuria (ETPKU), and late-diagnosed phenylketonuria (PKU)] compared with 76 HCs were examined using spectral-domain OCT. Indices of phenylalanine elevation and variability were correlated with OCT parameters. Late-diagnosed PKU patients showed reduced peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIPL) volume. Adult ETPKU patients were found to have lower GCIPL volume (p = 0.016), which correlated with the indices of phenylalanine control. In pediatric ETPKU patients with poor metabolic control, pRNFL was significantly reduced (p = 0.004). Patients with PAH deficiency not requiring treatment did not exhibit retinal degeneration. Inner nuclear layer (INL) was significantly increased in the pediatric ETPKU patients, driven by those with current poor metabolic control (p = 0.006). Our data provide evidence of retinal neuroaxonal degeneration and INL swelling, depending on the phenotype, current age, and metabolic control. These findings suggest that OCT is suitable to investigate neurodegeneration in PKU and we propose OCT as a sensitive, reliable, safe, low-burden, and low-cost examination for future multicenter studies.

Sexual dysfunction among men with diabetes mellitus attending chronic out-patient department at the three hospitals of Northwest Amhara region, Ethiopia: Prevalence and associated factors

Background Sexual dysfunction is the commonest reproductive health problem observed among men with diabetes mellitus affecting their quality of life. Previous studies conducted in this area were concentrated on the specific domains of sexual dysfunction, and factors were not well-addressed. Therefore, this study was aimed to determine the prevalence of all forms of sexual dysfunction and to identify its associated factors among diabetic men patients attending at the three hospitals of the Amhara region, Ethiopia. Method An institutional-based cross-sectional study was conducted involving 462 men diabetic patients at the three hospitals of the northwest Amhara region. A systemic random sampling technique was employed. A face-to-face interviewer-administered change in the sexual functioning questionnaire was used to collect the required data from the 20th of February to the 15th of April 2020. The binary logistic regression was employed and a multivariable logistic regressions model was used to control the effect of confounders. Variables that had an independent correlation with the sexual dysfunction were identified based on a p-value≤ 0.05. Likewise, the direction and strength of association were interpreted using Adjusted Odds Ratio (AOR) with its corresponding 95% CI. Results The prevalence of sexual dysfunction was found to be 69.5% (95%CI: (65.1–73.9)). The magnitude of sexual dysfunction was prevalently observed among participants who were older (> 50 years) (AOR = 8.7, 95%CI: (3.3–23.1)). Likewise, the odds of sexual dysfunction was significantly higher among men who have lived with diabetes for a longer duration (AOR = 10.8, 95%CI: (5.3–21.9)), with poor metabolic control (AOR = 3.57, 95%CI: (1.81–7.05)), with comorbid illnesses (AOR = 5.07, 95%CI: (2.16–11.9)), and diabetic-related complications (AOR = 3.01, 95%CI: 1.31–6.92). On the other hand, participants who were physically active (AOR = 0.41, 95%CI: (0.12–0.7)) and satisfied with their relationship (AOR = 0.15, 95%CI: (0.03–0.7)) showed a lesser risk of experiencing sexual dysfunction. Conclusion Well over two-thirds of men with diabetes mellitus have experienced sexual dysfunction, implying a public health pressing problem. Older age, lack of physical activity, living longer duration with diabetes, having diabetic complications, experiencing co-morbid illnesses, being unsatisfied with couple relationship, and poor metabolic control increased the risk of developing SD. Therefore, promoting physical exercise, preventing co-morbid illnesses, and couples counseling to build up a good couple relationship are recommended to promote the sexual and reproductive health of men with diabetes.

Videocapillaroscopy, Insulin-Induced Skin Lipohypertrophy, and Bruising: A Preliminary Approach

Background: Lipohypertrophy (LH) is a frequent cutaneous complication in people with insulin-treated type-2 DM (IT-T2DM). Its pathogenesis is not fully known, however. Retinal and kidney microangiopathy (MIA) is also frequent in such patients, especially in case of poor metabolic control. Aim: To assess whether specific nailfold video-capillaroscopy (NVC) patterns could be identified in MIA-affected IT-T2DM patients, thus eventually helping explain LH pathogenesis. Methods: 50 IT-T2DM patients with LH and 50 without LH undergoing NVC were enrolled. All followed a multiple daily injection regimen and had established retinal and renal microangiopathic complications. Results: While confirming expected MIA-related skin changes in both groups, our data failed to detect any specific NVC pattern in LH-affected patients yet showed the most severe NVC changes to be significantly associated with HbA1c values over 9%. Conclusion: Severe NVC-assessed MIA lesions reflect longstanding poor metabolic control in IT-T2DM rather than contributing to LH pathogenesis.

MALDI-TOF Protein Profiling Reflects Changes in Type 1 Diabetes Patients Depending on the Increased Amount of Adipose Tissue, Poor Control of Diabetes and the Presence of Chronic Complications

Introduction: Protein profiling allows the determination of the presence of proteins marking various stages of the disease, and differentiates between people at risk of various diseases. In type 1 diabetes, protein profiling had been previously used to find blood markers other than islet autoantibodies to indicate the pancreatic beta cell destruction process and to reflect the progression of type 1 diabetes mellitus (T1DM). However, T1DM is an auto-immune disease and its clinical presentation changes in time of its duration. The aim of the study: To find differences in protein profiles in patients with type 1 diabetes according to diabetes control (HbA1c > 7%) and with presence of diabetic complications or obesity. It may help to identify subgroups of patients who may need a better clinical supervision and individualized treatment. Material and methods: A group of 103 patients with auto-immunologically confirmed T1DM, and meeting the following inclusion criteria: Caucasian race, duration of diabetes >5 years, were used in the study. Criteria of exclusion: past or present cancer (treated with chemo-/radiotherapy), diseases of the liver (ALT > 3 × ULN) except for people with simple hepatic steatosis, chronic renal disease (eGFR < 30 mL/1.73 m2/min), and acute inflammation (CRP > 5 mg/dL). The study group was divided in terms of the presence of chronic complications, obesity, or poor metabolic control (HbA1c > 7%). Protein profiling was completed by using the MALDI-TOF MS (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) analyzer. Results: Differentiating proteins were identified in all of the groups. The groups burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Conclusion: The groups of type 1 diabetes patients burdened with complications, obesity, and poor metabolic control were characterized by increased levels of fibrinogen, complement C4 and C3. Further detailed studies are necessary to determine more subtle changes in the proteomic profile of patients with type 1 diabetes.

DNA Methylomes and Epigenetic Age Acceleration Associations with Poor Metabolic Control in T1D

Type 1 diabetes (T1D) is an autoimmune disease that leads to insulin deficiency and hyperglycemia. Little is known about how this metabolic dysfunction, which substantially alters the internal environment, forces cells to adapt through epigenetic mechanisms. Consequently, the purpose of this work was to study what changes occur in the epigenome of T1D patients after the onset of disease and in the context of poor metabolic control. We performed a genome-wide analysis of DNA methylation patterns in blood samples from 18 T1D patients with varying levels of metabolic control. We identified T1D-associated DNA methylation differences on more than 100 genes when compared with healthy controls. Interestingly, only T1D patients displaying poor glycemic control showed epigenetic age acceleration compared to healthy controls. The epigenetic alterations identified in this work make a valuable contribution to improving our understanding of T1D and to ensuring the appropriate management of the disease in relation to maintaining healthy aging.

Sexual Dysfunction Among Men With Diabetes Mellitus Attending Chronic Out-patient Department at the Three Hospitals of Northwest Amhara Region, Ethiopia: Prevalence and Associated Factors

Background: Sexual dysfunction is the commonest reproductive health problem seen among men with diabetes which has different health and social consequences. Previous studies conducted in this area were concentrated to specific domain of sexual dysfunction and factors were not well addressed.Objective: To determine the prevalence of sexual dysfunction and identify associated factors among men with diabetes at the three hospitals of Amhara region, Ethiopia.Methods: Institutional-based cross-sectional study was conducted among 462 men diabetic patients attending at the three hospitals of northwest Amhara region. Systemic random sampling were used and interviewer administered change in sexual functioning questionnaire were collected from February 20, 2020- April 15, 2020. The collected data were entered to Epi-data and analyzed by SPSS. Binary logistic regression was employed and multi-variable logistic regressions model used to control confounders. Variables that had independent correlation with the outcome were identified (with p-value≤ 0.05 and 95%CI) the direction and the strength of the association were measured by Adjusted Odds Ratio (AOR).Results: The prevalence of sexual dysfunction found to be 69.5% (95%CI= (65.1-73.9)). The magnitude of sexual dysfunction has been disproportionately observed among old age individuals (AOR=8.7, 95%CI: (3.3-23.1)), longer duration of diagnosis with diabetes(AOR=10.8, 95%CI: (5.3-21.9)), poor metabolic control (AOR=3.57, 95%CI: (1.81-7.05)), existence of comorbidities (AOR=5.07, 95%CI: (2.16–11.9)) and having diabetic related complications (AOR=3.01, 95%CI=1.31-6.92). Nevertheless, physically active (AOR=0.41, 95%CI: (0.12-0.7)) and couples satisfied with their relationship (AOR=0.15, 95%CI: (0.03-0.7)) were less likely to experience the problem.Conclusion: Well over two-thirds of men with diabetes have experienced sexual dysfunction, implying a public health pressing concern. Older individuals, physical in activity, longer duration of diagnosis with diabetes, having diabetic complication, experiencing co-morbid illnesses, couples un satisfaction, and poor metabolic control increased risk of developing SD. Therefore, promoting physical exercise, preventing co-morbid illnesses, couples counseling to build good relationship are recommended for combating the problem.

Morning specimen is not representative of metabolic control in Tunisian children with phenylketonuria: a repeated cross-sectional study

Objective and methodsTo evaluate variation of capillary phenylalanine concentrations over the day in patients treated for phenylketonuria and the reliability of the morning sample to assess metabolic control, we conducted a repeated cross-sectional study in 25 Tunisian patients on phenylalanine-low diet. For each patient, we collected nine capillary samples over the day. Phenylalanine was dosed by fluorimetry.ResultsThere was a wide variability of phenylalanine concentrations over the day (p<0.001). Compared to morning sample, phenylalanine concentration was significantly lower before lunch (p=0.038), after lunch (p=0.025), before dinner (p<0.001), after dinner (p=0.035) and at 4:00 a.m. (p=0.011). Compared to the 24 h sampling, the morning sample had a 68% to identify unbalanced patients. 60% of patients, had peak phenylalanine concentration after the morning. Half of the patients with normal morning phenylalanine concentration had low phenylalanine values over 8–20 h. Percentages of high phenylalanine concentrations over the last semester were higher in patients with poor metabolic control over the 24 h (21% ± 43 vs. 0% ± 9%); p=0.043.ConclusionA single morning sample gives an incomplete information on metabolic control in phenylketonuric patients. Using four pre-prandial samples on the day should be considered as alternative in patients with good metabolic control.

Large Neutral Amino Acids (LNAAs) Supplementation Improves Neuropsychological Performances in Adult Patients with Phenylketonuria

Phenylketonuria is an inborn error of phenylalanine (Phe) metabolism diagnosed by newborn screening and treated early with diet. Although diet prevents intellectual disability, patients often show impairment of executive functions, working memory, sustained attention, and cognitive flexibility. Large neutral amino acids (LNAAs) have been proposed as a dietary supplement for PKU adults. Few studies show that LNAAs may help in improving metabolic control as well as cognitive functions. In this study, 10 adult PKU patients with poor metabolic control were treated for 12 months with LNAAs (MovisCom, 0.8–1 g/kg/day) and underwent Phe and Tyrosine (Tyr) monitoring monthly. Neuropsychological assessment was performed at T0, T+3, and T+12 months by using the American Psychological General Well-Being Index, the Wisconsin Card Sorting Test, the Test of Attentional Performance, and the 9-Hole Peg Test. No change in plasma Phe levels was observed during LNAAs supplementation, while Tyr levels significantly improved during LNAAs supplementation (p = 0.03). Psychometric tests showed an improvement of distress and well-being rates, of executive functions, attention, and vigilance, whereas no difference was noted regarding hand dexterity. This study adds evidence of the advantage of LNAAs supplementation in improving cognitive functions and well-being in patients with PKU with poor metabolic control.