Search

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., (© 2024 The Author(s). Journal of the Peripheral Nervous System published by Wiley Periodicals LLC on behalf of Peripheral Nerve Society.)

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D)., Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm 2 ), corneal nerve branch density (CNBD, <21 branches/mm 2 ), and corneal nerve fiber length (CNFL, <16 mm/mm 2 ) persisting for ≥50% of the study duration., Results: A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage ( p  < 0.0001). Sustained corneal nerve damage was associated with the development of DPN ( p  < 0.0001), a progressive loss of vibration perception ( p  ≤ 0.05), an increased incidence of burning pain, numbness, or a combination of both ( p  = 0.01-0.001), and a borderline association with progressive sudomotor dysfunction ( p  = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9-86.8%, p  < 0.0001), while baseline and other sustained measures did not predict DPN onset., Conclusion: Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ponirakis, Al-Janahi, Elgassim, Homssi, Petropoulos, Gad, Khan, Zaghloul, Ali, Siddique, Mohamed, Ahmed, Dakroury, El Shewehy, Saeid, Mahjoub, Al-Thani, Ahmed, Hussein, Mahmoud, Hadid, Al Obaidan, Salivon, Mahfoud, Zirie, Al-Ansari, Atkin and Malik.)

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight ( n = 100), asthma with overweight or obesity ( n = 100), overweight or obesity ( n = 100), normal weight ( n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity ( n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal-Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher's exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma.

In our previous study, it was shown that endogenous vitamin D 3 and its metabolites are associated with diabetic microvascular complications and cardiovascular risk factors. The aim of the present study was to determine if the relationship between total vitamin D (vitamin D 2 supplements plus endogenous vitamin D 3 ) was a better predictor of complications in type 2 diabetes (T2DM). A total of 460 patients with T2DM participated in the present cross-sectional study. Plasma levels of total vitamin D and its metabolites (1,25-dihydroxyvitamin D (1,25(OH)D), 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)D) were measured by isotope-dilution liquid chromatography tandem mass spectrometry analysis. 1,25-dihydroxyvitamin D 3 and 25-hydroxyvitamin D 3 were associated with diabetic retinopathy and coronary artery disease, but total 1,25-dihydroxyvitamin D and total 25-hydroxyvitamin D levels were not statistically associated with any complications. Total 1,25-dihydroxyvitamin D showed the same positive association as 1,25-dihydroxyvitamin D 3 for hypertension and dyslipidemia, and total 25-hydroxyvitamin D showed the same positive association as 25-hydroxyvitamin D 3 for dyslipidemia. Total 24,25-dihydroxyvitamin D showed the same positive association only with dyslipidemia as did 24,25-dihydroxyvitamin D 3 . However, total 25-hydroxyvitamin D was associated with hypertension, whereas 25-hydroxyvitamin D 3 was not. Vitamin D 3 metabolites were associated with diabetic retinopathy, whereas total vitamin D levels were not, suggesting that endogenous vitamin D 3 metabolites are a better measure of diabetic microvascular complications. However, both total vitamin D and vitamin D 3 metabolites were associated with cardiovascular risk factors in patients with type 2 diabetes., (Copyright: © Ahmed et al.)

Background: Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications., Research Design and Methods: Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D 3 supplement naive. Plasma concentration of 25-hydroxyvitamin D 3 (25(OH)D 3 ) and its metabolites 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) and 24,25-dihydroxyvitamin D 3 (24,25(OH) 2 D 3 ) and its epimer, 3-epi-25-hydroxyvitamin D 3 (3-epi-25(OH)D 3 ), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH) 2 D 3 :25(OH)D 3 ; VMR-2 as a ratio of 1,25(OH) 2 D 3 :25(OH)D 3 ; VMR-3 was calculated as a ratio of 3-epi-25(OH)D 3 : 25(OH)D 3. RESULTS: An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p < 0.001), dyslipidemia (p < 0.001), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), coronary artery disease (p = 0.001) and stroke (p < 0.05). VMR-3 associated with hypertension (p < 0.05), dyslipidemia (p < 0.001) and coronary artery disease (p < 0.05)., Conclusions: In this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications.

Aims: Vitamin D measurement is a composite of vitamin D 2 (25(OH)D 2 ) and D 3 (25(OH)D 3 ) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D 2 supplements. This study was undertaken to determine if vitamin D 2 and D 3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D 2 and vitamin D 3 levels in subjects with T2DM . METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D 2 and D 3 were measured by LC-MS/MS analysis., Results: All subjects were taking vitamin D 2 and none were taking D 3 supplements. Vitamin D 2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D 3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D 2 nor vitamin D 3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D 2 and vitamin D 3 showed no difference., Conclusions: In this Qatari cohort, vitamin D 2 was associated with hypertension and dyslipidemia, whilst vitamin D 3 levels were associated with diabetic retinopathy. Vitamin D 2 levels were higher, whilst vitamin D 3 were lower in diabetics and females, likely due to ingestion of vitamin D 2 supplements.

Recruitment into clinical research studies is a major challenge. This study was carried out to explore the perceptions and attitudes towards clinical research participation among the general public in Qatar. A population based questionnaire study was carried out at public events held in Qatar. Residents of Qatar, 18 years or above in age were surveyed, anonymously, following verbal consent. Descriptive and multivariate analyses were conducted. We administered 2517 questionnaires to examine clinical research participation, of which 2379 complete forms were analyzed. Those who had previously been approached to participate in research completed a more detailed assessment. Data showed that only 5.7% participants (n = 134) had previously been approached to participate in a clinical research study. Of these 63.4% (n = 85) had agreed to participate while 36.6% (n = 49) had declined. The main reasons for declining participation included: time constraint (47.8%, n = 11), 'fear' (13.0%, n = 3), lack of awareness about clinical research (8.7%, n = 2) and lack of interest (8.7%, n = 2). 'To help others' (31.8%, n = 27) and 'thought it might improve my access to health care' (24.7%, n = 21) were the prime motivators for participation. There was a general agreement among participants that their previous research experience was associated with positive outcomes for self and others, that the research conduct was ethical, and that opportunities for participation will be welcomed in future. More than ten years of stay within Qatar was a statistically significant determinant of willingness to participate, adjusted odds ratio 5.82 (95% CI 1.93-17.55), p = 0.002. Clinical research participation in Qatar needs improvement. Time constraints, lack of trust in and poor awareness about clinical research are main barriers to participation. Altruism, and improved health access are reported as prime motivators. Deeper insight in to the factors affecting clinical research participation is needed to devise evidence based policies for improvement in recruitment strategies.