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Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Research article

Blood hemoglobin A1c levels and amyotrophic lateral sclerosis survival

Authors: Qian-Qian Wei, Yongping Chen, Bei Cao, Ru Wei Ou, Lingyu Zhang, Yanbing Hou, Xiang Gao, Huifang Shang

Published in: Molecular Neurodegeneration | Issue 1/2017

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Abstract

Background

There are inconsistences regarding the correlation between diabetes or fasting blood glucose concentrations and the risk and survival of amyotrophic lateral sclerosis (ALS) in the previous studies. Moreover, the association between hemoglobin A1c (HbA1c) levels, which reflect long-term glycemic status, and ALS survival was not examined.

Methods

A prospective cohort study including 450 Chinese sporadic ALS patients (254 men and 196 women; mean age: 55.4 y). We identified 223 deaths during average 1.6 years of follow-up. We assessed levels of fasting HbA1c (primary exposure) and glucose (secondary exposure) via ion exchange high-performance liquid chromatography and hexokinase/glucose-6-pgosphate dehydrogenase methods, respectively. Multivariate Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ALS mortality across the exposures.

Results

Our results indicated that, higher levels of HbA1c, but not fasting blood glucose concentrations, were significantly associated with higher risks of mortality. The adjusted HR was 1.40 (95% confidence interval (95% CI): 1.02–1.99) for HbA1c of 5.7–6.4%, and 2.06 (95% CI: 1.07–3.96) for HbA1c ≥6.5%, relative to HbA1c <5.7% (P trend =0.01), after adjustment for age, smoking, obesity, disease severity, site of onset, lifestyle, and other potential confounders. The adjusted HR was 1.38 (95% CI: 0.81–2.35, P trend =0.13) for fasting glucose concentrations ≥7.0 mmol/L vs <5.6 mmol/L. We did not observe any significant interactions between HbA1c levels and age, sex, smoking, body mass index, rate of disease progression of ALS, and site of onset (P-interactions >0.05 for all).

Conclusion

In this prospective study, we observed that individuals with higher HbA1c levels at the baseline had higher risk of mortality, which is independent of other known risk factors.
Literature
2.
go back to reference Dupuis L, Corcia P, Fergani A, Gonzalez De Aguilar JL, Bonnefont-Rousselot D, Bittar R, et al. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology. 2008;70:1004–9.CrossRefPubMed Dupuis L, Corcia P, Fergani A, Gonzalez De Aguilar JL, Bonnefont-Rousselot D, Bittar R, et al. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology. 2008;70:1004–9.CrossRefPubMed
3.
go back to reference O'Reilly EJ, Wang H, Weisskopf MG, Fitzgerald KC, Falcone G, McCullough ML, et al. Premorbid body mass index and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:205–11.CrossRefPubMed O'Reilly EJ, Wang H, Weisskopf MG, Fitzgerald KC, Falcone G, McCullough ML, et al. Premorbid body mass index and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:205–11.CrossRefPubMed
4.
go back to reference Scarmeas N, Shih T, Stern Y, Ottman R, Rowland LP. Premorbid weight, body mass, and varsity athletics in ALS. Neurology. 2002;59:773–5.CrossRefPubMed Scarmeas N, Shih T, Stern Y, Ottman R, Rowland LP. Premorbid weight, body mass, and varsity athletics in ALS. Neurology. 2002;59:773–5.CrossRefPubMed
5.
go back to reference Logroscino G. Motor neuron disease: Are diabetes and amyotrophic lateral sclerosis related? Nat Rev Neurol. 2015;11:488–90.CrossRefPubMed Logroscino G. Motor neuron disease: Are diabetes and amyotrophic lateral sclerosis related? Nat Rev Neurol. 2015;11:488–90.CrossRefPubMed
6.
go back to reference Sun Y, Lu CJ, Chen RC, Hou WH, Li CY. Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study. J Epidemiol. 2015;25:445–51.CrossRefPubMedPubMedCentral Sun Y, Lu CJ, Chen RC, Hou WH, Li CY. Risk of Amyotrophic Lateral Sclerosis in Patients With Diabetes: A Nationwide Population-Based Cohort Study. J Epidemiol. 2015;25:445–51.CrossRefPubMedPubMedCentral
7.
go back to reference Jawaid A, Salamone AR, Strutt AM, Murthy SB, Wheaton M, McDowell EJ, et al. ALS disease onset may occur later in patients with pre-morbid diabetes mellitus. Eur J Neurol. 2010;17:733–9.CrossRefPubMed Jawaid A, Salamone AR, Strutt AM, Murthy SB, Wheaton M, McDowell EJ, et al. ALS disease onset may occur later in patients with pre-morbid diabetes mellitus. Eur J Neurol. 2010;17:733–9.CrossRefPubMed
8.
go back to reference Kioumourtzoglou MA, Rotem RS, Seals RM, Gredal O, Hansen J, Weisskopf MG. Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study. JAMA Neurol. 2015;72:905–11.CrossRefPubMedPubMedCentral Kioumourtzoglou MA, Rotem RS, Seals RM, Gredal O, Hansen J, Weisskopf MG. Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study. JAMA Neurol. 2015;72:905–11.CrossRefPubMedPubMedCentral
9.
go back to reference Paganoni S, Hyman T, Shui A, Allred P, Harms M, Liu J, et al. Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis. Muscle Nerve. 2015;52:339–43.CrossRefPubMedPubMedCentral Paganoni S, Hyman T, Shui A, Allred P, Harms M, Liu J, et al. Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis. Muscle Nerve. 2015;52:339–43.CrossRefPubMedPubMedCentral
10.
go back to reference Lekoubou A, Matsha TE, Sobngwi E, Kengne AP. Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic review. BMC Res Notes. 2014;7:171.CrossRefPubMedPubMedCentral Lekoubou A, Matsha TE, Sobngwi E, Kengne AP. Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic review. BMC Res Notes. 2014;7:171.CrossRefPubMedPubMedCentral
11.
go back to reference Korner S, Kollewe K, Ilsemann J, Muller-Heine A, Dengler R, Krampfl K, et al. Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis. Eur J Neurol. 2013;20:647–54.CrossRefPubMed Korner S, Kollewe K, Ilsemann J, Muller-Heine A, Dengler R, Krampfl K, et al. Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis. Eur J Neurol. 2013;20:647–54.CrossRefPubMed
12.
go back to reference Pradat PF, Bruneteau G, Gordon PH, Dupuis L, Bonnefont-Rousselot D, Simon D, et al. Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11:166–71.CrossRefPubMed Pradat PF, Bruneteau G, Gordon PH, Dupuis L, Bonnefont-Rousselot D, Simon D, et al. Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11:166–71.CrossRefPubMed
13.
go back to reference Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights. 2016;11:95–104.PubMedPubMedCentral Sherwani SI, Khan HA, Ekhzaimy A, Masood A, Sakharkar MK. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark Insights. 2016;11:95–104.PubMedPubMedCentral
14.
go back to reference Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, Del Canizo-Gomez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes. 2014;5:444–70.CrossRefPubMedPubMedCentral Martin-Timon I, Sevillano-Collantes C, Segura-Galindo A, Del Canizo-Gomez FJ. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes. 2014;5:444–70.CrossRefPubMedPubMedCentral
15.
go back to reference Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293–9.CrossRefPubMed Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:293–9.CrossRefPubMed
16.
go back to reference American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34(Suppl 1):S62–9.CrossRef American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34(Suppl 1):S62–9.CrossRef
17.
go back to reference Diabetes, Chinese Medical Association (CMA). The guidelines for the diagnosis and treatment of diabetes in China. Chin J Diabetes. 2014;8:2–42. Diabetes, Chinese Medical Association (CMA). The guidelines for the diagnosis and treatment of diabetes in China. Chin J Diabetes. 2014;8:2–42.
18.
go back to reference Youngquist ST, McIntosh SE, Swanson ER, Barton ED. Air ambulance transport times and advanced cardiac life support interventions during the interfacility transfer of patients with acute ST-segment elevation myocardial infarction. Prehosp Emerg Care. 2010;14:292–9.CrossRefPubMed Youngquist ST, McIntosh SE, Swanson ER, Barton ED. Air ambulance transport times and advanced cardiac life support interventions during the interfacility transfer of patients with acute ST-segment elevation myocardial infarction. Prehosp Emerg Care. 2010;14:292–9.CrossRefPubMed
19.
go back to reference Weisskopf MG, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A. Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol. 2004;160:26–33.CrossRefPubMed Weisskopf MG, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A. Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol. 2004;160:26–33.CrossRefPubMed
20.
go back to reference Wei Q, Chen X, Zheng Z, Huang R, Guo X, Cao B, et al. Frontal lobe function and behavioral changes in amyotrophic lateral sclerosis: a study from Southwest China. J Neurol. 2014;261:2393–400.CrossRefPubMed Wei Q, Chen X, Zheng Z, Huang R, Guo X, Cao B, et al. Frontal lobe function and behavioral changes in amyotrophic lateral sclerosis: a study from Southwest China. J Neurol. 2014;261:2393–400.CrossRefPubMed
21.
go back to reference Wei Q, Chen X, Zheng Z, Huang R, Guo X, Cao B, et al. Screening for cognitive impairment in a Chinese ALS population. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:40–5.CrossRefPubMed Wei Q, Chen X, Zheng Z, Huang R, Guo X, Cao B, et al. Screening for cognitive impairment in a Chinese ALS population. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16:40–5.CrossRefPubMed
22.
go back to reference Chio A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009;10:310–23.CrossRefPubMedPubMedCentral Chio A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E, et al. Prognostic factors in ALS: A critical review. Amyotroph Lateral Scler. 2009;10:310–23.CrossRefPubMedPubMedCentral
23.
go back to reference Zoccolella S, Beghi E, Palagano G, Fraddosio A, Guerra V, Samarelli V, et al. Riluzole and amyotrophic lateral sclerosis survival: a population-based study in southern Italy. Eur J Neurol. 2007;14:262–8.CrossRefPubMed Zoccolella S, Beghi E, Palagano G, Fraddosio A, Guerra V, Samarelli V, et al. Riluzole and amyotrophic lateral sclerosis survival: a population-based study in southern Italy. Eur J Neurol. 2007;14:262–8.CrossRefPubMed
24.
go back to reference Cudkowicz ME, Titus S, Kearney M, Yu H, Sherman A, Schoenfeld D, et al. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13:1083–91.CrossRefPubMedPubMedCentral Cudkowicz ME, Titus S, Kearney M, Yu H, Sherman A, Schoenfeld D, et al. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13:1083–91.CrossRefPubMedPubMedCentral
25.
go back to reference Committee IE. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–34.CrossRef Committee IE. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–34.CrossRef
26.
go back to reference Dorst J, Kuhnlein P, Hendrich C, Kassubek J, Sperfeld AD, Ludolph AC. Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol. 2011;258:613–7.CrossRefPubMed Dorst J, Kuhnlein P, Hendrich C, Kassubek J, Sperfeld AD, Ludolph AC. Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol. 2011;258:613–7.CrossRefPubMed
27.
go back to reference Lin JD, Chang JB, Wu CZ, Pei D, Hsieh CH, Hsieh AT, et al. Identification of insulin resistance in subjects with normal glucose tolerance. Ann Acad Med Singap. 2014;43:113–9.PubMed Lin JD, Chang JB, Wu CZ, Pei D, Hsieh CH, Hsieh AT, et al. Identification of insulin resistance in subjects with normal glucose tolerance. Ann Acad Med Singap. 2014;43:113–9.PubMed
28.
go back to reference Borai A, Livingstone C, Abdelaal F, Bawazeer A, Keti V, Ferns G. The relationship between glycosylated haemoglobin (HbA1c) and measures of insulin resistance across a range of glucose tolerance. Scand J Clin Lab Invest. 2011;71:168–72.CrossRefPubMed Borai A, Livingstone C, Abdelaal F, Bawazeer A, Keti V, Ferns G. The relationship between glycosylated haemoglobin (HbA1c) and measures of insulin resistance across a range of glucose tolerance. Scand J Clin Lab Invest. 2011;71:168–72.CrossRefPubMed
29.
go back to reference Shi P, Wei Y, Zhang J, Gal J, Zhu H. Mitochondrial dysfunction is a converging point of multiple pathological pathways in amyotrophic lateral sclerosis. J Alzheimers Dis. 2010;20(Suppl 2):S311–24.CrossRefPubMed Shi P, Wei Y, Zhang J, Gal J, Zhu H. Mitochondrial dysfunction is a converging point of multiple pathological pathways in amyotrophic lateral sclerosis. J Alzheimers Dis. 2010;20(Suppl 2):S311–24.CrossRefPubMed
30.
go back to reference Abdul-Ghani MA, DeFronzo RA. Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus. Curr Diabetes Rep. 2008;8:173–8.CrossRef Abdul-Ghani MA, DeFronzo RA. Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus. Curr Diabetes Rep. 2008;8:173–8.CrossRef
31.
go back to reference Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Sign. 2010;12:537–77.CrossRef Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Sign. 2010;12:537–77.CrossRef
32.
go back to reference Park K, Gross M, Lee DH, Holvoet P, Himes JH, Shikany JM, et al. Oxidative stress and insulin resistance: the coronary artery risk development in young adults study. Diabetes Care. 2009;32:1302–7.CrossRefPubMedPubMedCentral Park K, Gross M, Lee DH, Holvoet P, Himes JH, Shikany JM, et al. Oxidative stress and insulin resistance: the coronary artery risk development in young adults study. Diabetes Care. 2009;32:1302–7.CrossRefPubMedPubMedCentral
33.
go back to reference Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radical Bio Med. 2010;48:629–41.CrossRef Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radical Bio Med. 2010;48:629–41.CrossRef
34.
go back to reference English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia. 2015;58:1409–21.CrossRefPubMed English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia. 2015;58:1409–21.CrossRefPubMed
35.
go back to reference Mariosa D, Kamel F, Bellocco R, Ye W, Fang F. Association between diabetes and amyotrophic lateral sclerosis in Sweden. Eur J Neurol. 2015;22:1436–42.CrossRefPubMedPubMedCentral Mariosa D, Kamel F, Bellocco R, Ye W, Fang F. Association between diabetes and amyotrophic lateral sclerosis in Sweden. Eur J Neurol. 2015;22:1436–42.CrossRefPubMedPubMedCentral
36.
go back to reference Turner MR, Goldacre R, Ramagopalan S, Talbot K, Goldacre MJ. Autoimmune disease preceding amyotrophic lateral sclerosis: an epidemiologic study. Neurology. 2013;81(14):1222–5.CrossRefPubMedPubMedCentral Turner MR, Goldacre R, Ramagopalan S, Talbot K, Goldacre MJ. Autoimmune disease preceding amyotrophic lateral sclerosis: an epidemiologic study. Neurology. 2013;81(14):1222–5.CrossRefPubMedPubMedCentral
37.
go back to reference Chen Y, Lin Z, Chen X, Cao B, Wei Q, Ou R, et al. Large C9orf72 repeat expansions are seen in Chinese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2016;38(217):e15–22. Chen Y, Lin Z, Chen X, Cao B, Wei Q, Ou R, et al. Large C9orf72 repeat expansions are seen in Chinese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2016;38(217):e15–22.
38.
go back to reference Williams KL, McCann EP, Fifita JA, Zhang K, Duncan EL, Leo PJ, et al. Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin. Neurobiol Aging. 2015;36(3334):e1–5. Williams KL, McCann EP, Fifita JA, Zhang K, Duncan EL, Leo PJ, et al. Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin. Neurobiol Aging. 2015;36(3334):e1–5.
39.
go back to reference Konno T, Shiga A, Tsujino A, Sugai A, Kato T, Kanai K, et al. Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72. J Neurol Neurosurg Psychiatry. 2013;84:398–401.CrossRefPubMed Konno T, Shiga A, Tsujino A, Sugai A, Kato T, Kanai K, et al. Japanese amyotrophic lateral sclerosis patients with GGGGCC hexanucleotide repeat expansion in C9ORF72. J Neurol Neurosurg Psychiatry. 2013;84:398–401.CrossRefPubMed
40.
go back to reference Alavi A, Nafissi S, Rohani M, Shahidi G, Zamani B, Shamshiri H, et al. Repeat expansion in C9ORF72 is not a major cause of amyotrophic lateral sclerosis among Iranian patients. Neurobiol Aging. 2014;35(267):e1–7. Alavi A, Nafissi S, Rohani M, Shahidi G, Zamani B, Shamshiri H, et al. Repeat expansion in C9ORF72 is not a major cause of amyotrophic lateral sclerosis among Iranian patients. Neurobiol Aging. 2014;35(267):e1–7.
41.
go back to reference Consultation. WE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.CrossRef Consultation. WE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157–63.CrossRef
Metadata
Title
Blood hemoglobin A1c levels and amyotrophic lateral sclerosis survival
Authors
Qian-Qian Wei
Yongping Chen
Bei Cao
Ru Wei Ou
Lingyu Zhang
Yanbing Hou
Xiang Gao
Huifang Shang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0211-y

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