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Shortening of the leucocytes’ telomeres length in T2DM independent of age and telomerase activity

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Abstract

Aims

This study aimed to examine the role of plasma telomerase (TE), plasma insulin, patient’s age and disease duration in determination of the leucocytes’ telomeres length (LTL) in T2DM.

Methods

Blood samples from Kuwaiti patients with T2DM (110) and non-diabetic subjects (94) were analyzed by SYBR Green Quantitative PCR for estimation of the Absolute Human Telomere Length and by ELISA for estimation of the TE activity and insulin level. The body mass index (BMI) and HOMA-IR were calculated.

Results

The results revealed marked shortening of the LTL in T2DM compared with the non-diabetic subjects (6.068, 2.276–11.652 vs. 10.979, 6.495–23.402 kb), p < 0.001, while the TE concentration was comparable between the two groups (3.16, 0.00–6.02 vs. 4.16, 1.38–7.94 U/L, respectively), p 0.100. Importantly, in T2DM the LTL did not vary significantly with the disease duration (1 month to 40 years), p 0.959, and did not correlate with age, BMI, insulin-resistance, or glycemic parameters. Interestingly, there was a positive correlation between the LTL and insulin levels in T2DM (CC 0.211, p 0.0419). Finally, in non-diabetic subjects, HbA1c ≥ 6% was associated significantly with shorter LTL, this observation together with the lack of association of the LTL with the disease duration, suggests a causal role of short telomeres in T2DM development.

Conclusions

This study confirmed the LTL shortening in T2DM in Kuwaiti Arabs, and showed that the LTL was independent of age and TE activity but positively influenced by insulin levels. Furthermore, the study suggested that telomeres shortening could be a risk factor for T2DM.

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Abbreviations

BMI:

Body mass index

bp:

Base pair

ELISA:

Enzyme-linked immunosorbent assay

FBG:

The fasting plasma glucose

HbA1c:

Glycated hemoglobin

HDL-C:

High-density lipoprotein cholesterol

HOMA-IR:

Homeostatic model assessment of insulin resistance

HRP:

Horseradish peroxidase

Kb:

Kilobase pair

KW:

Kruskal–Wallis one way analysis of variance on ranks

LDL-C:

Low-density lipoprotein cholesterol

LTL:

Leucocytes telomeres length

MW:

Mann–Whitney rank sum test

OD:

Optical density

PCR:

Polymerase chain reaction

PHD:

Parental history of diabetes

PPMC:

Pearson product moment correlation

qPCR:

Quantitative PCR

SCR:

Single copy reference

T2DM:

Type 2 diabetes mellitus

TAG:

Triacylglycerol

TC:

Total cholesterol

TE:

Telomerase enzyme

TERC:

Telomere RNA component

TERT:

Telomere reverse transcriptase

TL:

Telomere length

WHO:

World health organization

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Acknowledgements

The authors would like to acknowledge the contribution of the study subject, patients and healthy volunteers, the medical and technical staff of the Kuwait hospitals and health centers, and the Ministry of Health authorities in Kuwait. We greatly appreciate the role of the senior specialist in Arabian Gulf University, Ahmed Ramzi for technical support. All costs related to the project were paid by the Kuwait cultural office in Bahrain.

Funding

Kuwait cultural office in Bahrain.

Author information

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine and Medical Sciences (CMMS), Arabian Gulf University (AGU), P.O. Box 26671, Manama, Kingdom of Bahrain

    Dhuha M. B. AlDehaini, Muhalab E. Ali, Zainab Hasan Abdulla Malalla, Mai Sater & Hayder A. Giha

  2. Biochemistry Laboratory, Farwaniya Hospital, P.O. Box. 13373, 81004, Farwaniya, Kuwait

    Dhuha M. B. AlDehaini

  3. Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait City, Kuwait

    Suzanne A. Al-Bustan

Authors
  1. Dhuha M. B. AlDehaini
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  2. Suzanne A. Al-Bustan
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  3. Muhalab E. Ali
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  4. Zainab Hasan Abdulla Malalla
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  5. Mai Sater
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  6. Hayder A. Giha
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Contributions

HAG, DMBA, SAA, and MS developed the research idea and study design and supported the project at different levels. DMBA, and SAA involved in samples collection. DMBA, ZHA, and MEA conducted the laboratory work. HAG, DMBA, SAA, and MS conducted and revised the statistical analysis. HAG, DMBA, ZHA, and MEA contributed to the manuscript draft, and all authors revised and added to the draft and contributed to the final version of the manuscript.

Corresponding author

Correspondence to Hayder A. Giha.

Ethics declarations

Conflict of interests

All authors declare that they have no competing interests.

Ethical standard statement or human and animal rights

All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the Research Committee of Kuwait Ministry of Health (2015/242) and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

A verbal informed consent was obtained from each study subject for publication.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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AlDehaini, D.M.B., Al-Bustan, S.A., Ali, M.E. et al. Shortening of the leucocytes’ telomeres length in T2DM independent of age and telomerase activity. Acta Diabetol 57, 1287–1295 (2020). https://doi.org/10.1007/s00592-020-01550-4

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  • DOI: https://doi.org/10.1007/s00592-020-01550-4

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