No abstract

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30–40 ng/mL, improves endothelial function in Singapore’s multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20–30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index–endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student’s t-test or Kruskal–Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

Context and objective Thyroid autoimmunity has been reported to be associated with SARS-CoV-2 and the SARS-CoV-2 vaccination recently. We report a series of patients who presented with new onset or relapse of Graves’ disease related hyperthyroidism shortly after receiving the SARS-CoV-2 mRNA vaccine at a single tertiary institution in Singapore. Methods and results We describe 12 patients who developed hyperthyroidism within a relatively short interval (median onset of 17 (range: 5 - 63) days) after receiving the SARS-CoV-2 mRNA vaccine. The majority were females (11/12) with median age of 35.5 (range: 22-74) years. Six patients had new onset hyperthyroidism, while the other six had relapse of previously well-controlled Graves’ disease. TSH Receptor antibody concentrations ranged from 2.4-32 IU/L. Majority of the patients were able to go for the second dose of the vaccine without any further exacerbations. Literature review revealed 21 other similar cases reported from across the world. Conclusion Our case series provide insight into the characteristics of individuals in whom Graves’ disease was triggered by the SARS-CoV-2 vaccination. Clinicians need to be vigilant of precipitation or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the SARS-CoV-2 vaccination. Further epidemiological and mechanistic studies are required to elucidate the possible associations between the SARS-CoV-2 vaccines and the development of thyroid autoimmunity.

The haptoglobin 2-2 genotype is associated with atherosclerosis in type 2 diabetes mellitus. We examined the associations of the haptoglobin 2-2 genotype with C-reactive protein (high-sensitivity C-reactive protein) and carotid artery intima-media thickness, adjusting for age, gender, ethnicity, type 2 diabetes mellitus, smoking status, body mass index, blood pressure, glycated haemoglobin, non-high-density lipoprotein cholesterol and medications via logistic multivariate regression in 200 subjects (160 type 2 diabetes mellitus versus 40 healthy individuals). The prevalence of the haptoglobin 2-2 genotype was 58% (115/200), higher in the Indians than in Chinese (72% versus 45%, p = 0.001). Multivariate analysis showed that the haptoglobin 2-2 genotype was associated with high-sensitivity C-reactive protein [mean: 3.5 ± 3.9 versus 2.2 ± 2.6 mg/L (non-haptoglobin 2-2), p < 0.001], haptoglobin concentration [mean: 116.9 ± 54.4.0 versus 147.2 ± 54.5 mg/dL (non-haptoglobin 2-2), p < 0.001] and average carotid artery intima-media thickness (multiplied by 10) [6.15 ± 1.22 versus 5.98 ± 1.20 mm (non-haptoglobin 2-2), p = 0.013]. This pilot study shows an association of the haptoglobin 2-2 genotype with low-grade inflammation, haptoglobin concentration and carotid artery intima-media thickness in multi-ethnic Singapore.

Aims: Vitamin E (Vit-E) may preferentially improve cardiovascular risk in haptoglobin 2-2 (Hp2-2) genotype diabetes individuals. We studied the impact of Vit-E supplementation on vascular function in diabetes individuals stratified by haptoglobin genotype in Singapore. Methods: In this 24-week, double blind, placebo-controlled RCT, we recruited 187 subjects (101 Hp2-2, 86 non-Hp2-2). Intervention: alpha-tocopherol-400 IU. Primary Outcome: Change in EndoPAT-derived reactive-hyperaemia index (RHI) and augmentation index (AIx); Secondary Outcomes: Pulse-Wave velocity (Sphygmocor-PWV), carotid intima media thickness (CIMT), inflammation (hsCRP), derivatives of reactive-oxygen metabolites (dROMs), biological antioxidantpotential (BAPs), HbA1c, LDL-C, HDL-C and oxidised LDL-C (ox-LDL). Results: Overall, with Vit-E supplementation no significant change in RHI, PWV, CIMT, hsCRP, dROMS, BAPs, HDL-C and HbA1c was observed (p > 0.05); an increase in LDL-C with concomitant decrease in ox-LDL, and incidentally increase in eGFR was observed (p < 0.05). No interaction effect with haptoglobin genotype was seen for all outcomes (p > 0.05). Subgroup analysis: In the non-Hp-2-2 group, Vit-E supplementation led to a higher EndoPAT-derived AIx, accompanied by higher LDL and ox-LDL concentrations (p < 0.05); Hp2-2 group: Vit-E supplementation led to higher eGFR when compared to the non-Hp2-2 group (exploratory) (p < 0.05). We observed an interaction effect for baseline haptoglobin concentration (threshold > 119 mg/dl) with intervention in terms of increased EndoPAT-derived AIx in the Hp > 119 mg/dl group whereas no change in the group with Hp ≤ 119 mg/dl. Conclusion: Vit-E supplementation did not show any preferential benefit or deleterious effect on vascular function in Hp2-2 diabetes subjects in Singapore. A possible deleterious effect of an increase in arterial stiffness in individuals with Hp > 119 mg/dl was observed. Future studies should consider personalisation based on baseline Hp concentrations in patients with T2DM rather than just Hp2-2 genotype to evaluate impact on the detailed lipid pathways, cardiac and renal physiology. The impact of ethnic differences needs to be explored in greater details.