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. 2022 Oct;14(10):646-657.
doi: 10.1111/1753-0407.13318. Epub 2022 Oct 4.

Protein pyrrole adducts are associated with elevated glucose indices and clinical features of diabetic diffuse neuropathies

Xiao Chen  1 , Zhuyi Jiang  2 , Lianjing Zhang  1   3 , Wei Liu  1 , Xiaohu Ren  1 , Luling Nie  1 , Desheng Wu  1 , Zhiwei Guo  4 , Weimin Liu  5 , Xifei Yang  1 , Yan Wu  2 , Zhen Liang  2 , Peter Spencer  6 , Jianjun Liu  1   3
Affiliations

Protein pyrrole adducts are associated with elevated glucose indices and clinical features of diabetic diffuse neuropathies

Xiao Chen et al. J Diabetes. 2022 Oct.

Abstract
in English, Chinese

Introduction: Diabetic neuropathy is the most prevalent complication of diabetes mellitus. Although the precise etiology of this neurological disorder has yet to be defined, elevated blood glucose promotes anerobic glycolysis; this produces excess advanced glycation end-products, many of which have a pyrrole structure. Here, we test the hypothesis that protein pyrrole adducts are associated with elevated glucose indices and some clinical features of diabetic diffuse neuropathies.

Method: We investigated the levels of plasma pyrrole adducts and adjusted urinary pyrrole adducts in a group of elderly persons (n = 516, age 60-79) residing in the District of Luohu, Shenzhen, China between 2017 and 2018. Symptoms of distal symmetric polyneuropathy (DSPN) and resting heart rate, a measure of autonomic nervous system function, were collected from participants (n = 258) with elevated glucose indices.

Result: Protein pyrrole adducts showed a strong correlation with glucose indices before and after adjustment for age and estimated glomerular filtration rates. Stratified analysis showed that the medians and interquartile values of pyrrole adducts grew as glucose indices of the subgroups increased. Participants with symptoms of DSPN and sinus tachycardia presented elevated levels of plasma pyrrole adducts.

Conclusion: This study provides a novel link between glucose indices and the etiology of diabetic diffuse neuropathies.

背景: 糖尿病神经病变是糖尿病最常见的并发症。虽然这种神经系统疾病的确切病因尚未确定，但血糖升高会促进无氧糖酵解, 这会产生过量的糖基化终产物，其中许多具有吡咯结构。在本文中，我们探究了吡咯蛋白加合物与血糖指数升高和糖尿病弥漫性神经病的一些临床特征的相关性。 方法: 我们调查了2017年至2018年间居住在中国深圳罗湖区的一组老年人(n = 516，年龄 60-79)的血浆吡咯加合物和校正尿吡咯加合物的水平。从血糖指数升高的参与者 (n=258) 中收集远端对称性多发性神经病(DSPN)的症状以及静息心率(衡量自主神经系统功能的指标)。 结果: 蛋白质吡咯加合物在校正年龄和估计肾小球滤过率前后与葡萄糖指数有很强的相关性。分层分析表明，吡咯加合物的中位数和四分位数随着亚组葡萄糖指数的增加而增加。有 DSPN 和窦性心动过速症状的参与者血浆吡咯加合物水平升高。 结论: 本研究提供了血糖指数与糖尿病弥漫性神经病病因学之间的新关联。.

Keywords: axonopathy; diabetic neuropathy; gamma-diketone; protein pyrrole adduct; γ-二酮; 糖尿病性神经病变; 蛋白质吡咯加合物; 轴突病.

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Figures

FIGURE 1
FIGURE 1
Flow chart of the process of inclusion and exclusion of participants in the study. DSPN, distal symmetric polyneuropathy; ECG, electrocardiography; FBG, fasting blood glucose; HbA1C, glycate hemoglobinA1C
FIGURE 2
FIGURE 2
Associations between glucose indices and pyrrole adducts (filled circle): fasting blood glucose (FBG) (A, C) and glycate hemoglobin A1c (HbA1C) (B, D) were significantly associated with plasma pyrrole adducts (PP) (A, B) and adjusted urinary pyrrole adducts (aUP) (C, D). After adjustment for age and estimated glomerular filtration rate (eGFR) (filled triangle), FBG (E, G) and HbA1C (F, H) were significantly associated with reciprocal levels of PP (E, F) and aUP (G, H).
FIGURE 3
FIGURE 3
Violin plots of stratified analyses for fasting blood glucose (FBG) (A, C) and glycate hemoglobin A1c (HbA1C) (B, D) on the levels of plasma pyrrole adducts (PP) (A, B) and adjusted urinary pyrrole adducts (C, D). Name and size of subgroups on the level of PP stratified by FBG: subgroup 1 (FBG = 4–6.99 mM, n = 253), subgroup 2 (FBG = 7–9.99 mM, n = 176), subgroup 3 (FBG = 10–14.99 mM, n = 68), and subgroup 4 (FBG ≥ 15 mM, n = 8). Subgroup analysis of PP stratified by HbA1c: subgroup 1 (HbA1c = 4.5–6.4%, n = 253), subgroup 2 (HbA1c = 6.5–7.4%, n = 89), subgroup 3 (HbA1c = 7.5–8.4%, n = 74), subgroup 4 (HbA1c = 8.5–9.4%, n = 42), subgroup 5 (HbA1c = 9.5–10.4%, n = 28), and subgroup 6 (HbA1c ≥ 10.5%, n = 19). Name and size of subgroups on the level of adjusted urinary pyrrole adducts (aUP) stratified by FBG: subgroup 1 (FBG = 4–6.99 mM, n = 255), subgroup 2 (FBG = 7–9.99 mM, n = 180), subgroup 3 (FBG = 10–14.99 mM, n = 69), and subgroup 4 (FBG ≥ 15 mM, n = 9). Subgroup analysis of aUP stratified by HbA1c: Subgroup 1 (HbA1c = 4.5–6.4%, n = 255), subgroup 2 (HbA1c = 6.5–7.4%, n = 92), subgroup 3 (HbA1c = 7.5–8.4%, n = 75), subgroup 4 (HbA1c = 8.5–9.4%, n = 42), subgroup 5 (HbA1c = 9.5–10.4%, n = 29), and subgroup 6 (HbA1c ≥ 10.5%, n = 20). The thin line of each violin represents the upper and the lower adjacent values of the subgroup, and the box in each violin represents the first interquartile (the lower line), the median value (the middle line), and the third interquartile (the upper line) of the subgroup. *p < .05; **p < .01***; p < .001
FIGURE 4
FIGURE 4
Violin plots of distal symmetric polyneuropathy (DSPN) symptom‐stratified analyses on the levels of plasma pyrrole adducts (PP) (A) and adjusted urinary pyrrole adducts (aUP) (B). The group with positive DSPN symptom, n = 16 for PP and n = 16 for aUP; the group with negative DSPN symptom, n = 101 for PP and n = 105 for aUP. The thin line of each violin represents the upper and the lower adjacent values of the subgroup, and the box in each violin represents the first interquartile (the lower line), the median value (the middle line), and the third interquartile (the upper line) of the subgroup. *p < .05
FIGURE 5
FIGURE 5
Violin plots of resting heart rate‐stratified analyses on the levels of plasma pyrrole adducts (PP) (A) and adjusted urinary pyrrole adducts (aUP) (B). The thin line of each violin represents the upper and the lower adjacent values of the subgroup, and the box in each violin represents the first interquartile (the lower line), the median value (the middle line), and the third interquartile (the upper line) of the subgroup. The group with sinus tachycardia, n = 20 for PP and n = 21 for aUP; the group with normal heart rate, n = 192 for PP and n = 197 for aUP. *p < .05
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References

    1. National Diabetes Statistics Report . 2020. Estimates of Diabetes and Its Burden in the United States. U.S. Department of Health & Human Services, Centers for Disease Control and Prevention. 2 and 5. https://www.cdc.gov/diabetes/data/statistics-report/index.html
    1. Saeedi P, Petersohn I, Salpea P, et al. Committee IDFDA: global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. - PubMed
    1. Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: new aspects of pathogenesis and their treatment implications. J Diabetes Investig. 2018;9:1239‐1254. - PMC - PubMed
    1. Pop‐Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40:136‐154. - PMC - PubMed
    1. Lee WJ, Jang S, Lee SH, Lee HS. Correlation between the severity of diabetic peripheral polyneuropathy and glycosylated hemoglobin levels: a quantitative study. Ann Rehabil Med. 2016;40:263‐270. - PMC - PubMed