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Relationship between obstructive sleep apnea syndrome and functional capacity in patients with diabetes mellitus type 2: an observational transversal study

SUMMARY

OBJECTIVE:

The aim of this study was to verify the association among obstructive sleep apnea, functional capacity, and metabolic control.

METHODS:

This was a cross-sectional study involving individuals of both sexes with clinical diagnosis of diabetes mellitus type 2 who were above 18 years of age. The assessment consisted of a volunteer identification form, a 2-minute step test, and the Stop-Bang questionnaire. In order to assess metabolic control, HbA1c and fasting glucose data were collected from medical records.

RESULTS:

A total of 100 individuals with diabetes mellitus type 2, of whom 61% were women, were included in this study. According to the Stop-Bang instrument, 26, 57, and 17% of patients had low, intermediate, and high risk of developing OSA, respectively. There was no association between the 2-minute step test and metabolic variables and diabetes mellitus type 2 chronicity with Stop-Bang.

CONCLUSIONS:

We concluded that there is no association among obstructive sleep apnea measured by means of Stop-Bang instrument, functional capacity measured by means of 2-minute step test, and metabolic variables in individuals with diabetes mellitus type 2.

KEYWORDS:
Sleep apnea; Diabetes mellitus; Exercise test; Metabolic disease

INTRODUCTION

Obstructive sleep apnea (OSA) syndrome is a chronic disorder of multifactorial etiology that affects about 2-4% of the adult population, and it is characterized by partial or total airway occlusion during sleep, related to anatomical changes of the respiratory tract, neuromuscular factors, and genetic predisposition, with consequent reduction or cessation of airflow, thus causing respiratory arrest for 10 s or more11. Garvey JF, Pengo MF, Drakatos P, Kent BD. Epidemiological aspects of obstructive sleep apnea. J Thorac Dis. 2015;7(5):920-9. https://doi.org/10.3978/j.issn.2072-1439.2015.04.52
https://doi.org/https://doi.org/10.3978/...
,22. Foroughi M, Razavi H, Malekmohammad M, Naghan PA, Jamaati H. Diagnosis of obstructive sleep apnea syndrome in adults: a brief review of existing data for practice in Iran. Tanaffos. 2016;15(2):70-4. PMID: 27904537.

Among the associated pathologies, diabetes mellitus (DM) often presents itself as a disorder that coexists with OSA, and this coexistence is justified with the risk factors shared with other disorders, such as obesity. In addition, studies indicate that short sleep duration is associated with decreased glucose tolerance, insulin sensitivity, and a consequently increased risk of developing diabetes33. Spiegel K, Leproult E, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435-9. https://doi.org/10.1016/s0140-6736(99)01376-8
https://doi.org/https://doi.org/10.1016/...
,44. Donga E, van Dijk M, van Dijk JG, Biermasz NR, Lammers GJ, van Kralingen K, et al. Partial sleep restriction decreases insulin sensitivity in type 1 diabetes. Diabetes Care. 2010;33(7):1573-7. https://doi.org/10.2337/dc09-2317
https://doi.org/https://doi.org/10.2337/...
,55. Buxton OM, Pavlova M, Reid EW, Wang W, Simonson DC, Adler GK. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes. 2010;59(9):2126-33. https://doi.org/10.2337/db09-0699
https://doi.org/https://doi.org/10.2337/...
,66. Doumit J, Prasad B. Sleep apnea in type 2 diabetes. Diabetes Spectr. 2016;29(1):14-9. https://doi.org/10.2337/diaspect.29.1.14
https://doi.org/https://doi.org/10.2337/...
. Furthermore, research suggests that diabetic patients are more likely to sleep during the day than nondiabetic patients and are more likely to be involved in traffic accidents due to daytime sleepiness77. Hayashino Y, Yamazaki S, Nakayama T, Sokejima S, Fukuhara S. Relationship between diabetes mellitus and excessive sleepiness during driving. Exp Clin Endocrinol Diabetes. 2008;116(1):1-5. https://doi.org/10.1055/s-2007-984442
https://doi.org/https://doi.org/10.1055/...
.

Polysomnography, although considered the gold standard for diagnosing this syndrome, is of high cost and is difficult to access. In this sense, low-cost instruments, easy applicability, and availability have been used, as is the case with questionnaires. Thus, the Stop-Bang questionnaire demonstrated good sensitivity and specificity in screening for this syndrome22. Foroughi M, Razavi H, Malekmohammad M, Naghan PA, Jamaati H. Diagnosis of obstructive sleep apnea syndrome in adults: a brief review of existing data for practice in Iran. Tanaffos. 2016;15(2):70-4. PMID: 27904537,88. Duarte RLM, Fonseca LBM, Magalhães-da-Silveira FJ, Silveira EA, Rabahi MG. Validação do questionário STOP-Bang para a identificação de apneia obstrutiva do sono em adultos no Brasil. J Bras Pneumol. 2017;43(6):456-63. https://doi.org/10.1590/s1806-37562017000000139
https://doi.org/https://doi.org/10.1590/...
.

Functional capacity may be negatively affected in individuals with OSA associated with fatigue, excessive sleepiness, excess weight, and low energy, which characterize the clinical presentation of the pathology99. Mendelson M, Bailly S, Marillier M, Flore P, Borel JC, Vivodtzev I, et al. Obstructive sleep apnea syndrome, objectively measured physical activity and exercise training interventions: a systematic review and meta-analysis. Front Neurol. 2018;9:73. https://doi.org/10.3389/fneur.2018.00073
https://doi.org/https://doi.org/10.3389/...
. Therefore, the 2-minute step test (2MST) appears as an alternative way to assess the functional capacity of an individual, considering that the ability to walk reflects the ability to maintain a series of activities of daily living in addition to enabling knowledge of the functional profile and the ability to guide decision-making in strategies aimed at preventing disabilities1010. Ben Saad H, Ben Hassen I, Ghannouchi I, Latiri I, Rouatbi S, Escourrou P, et al. 6-min walk-test data in severe obstructive-sleep-apnea-hypopnea-syndrome (OSAHS) under continuous-positive-airway-pressure (CPAP) Treatment. Respir Med. 2015;109(5):642-655. https://doi.org/10.1016/j.rmed.2015.03.001
https://doi.org/https://doi.org/10.1016/...
,1111. Guedes MBOG, Lopes JM, Andrade AS, Guedes TSR, Ribeiro JM, Cortez LCA. Validation of the two-minute step test for diagnosis of the functional capacity of hypertensive elderly persons. Rev Bras Geriatr Gerontol. 2015;18(4):921-6. http://doi.org/10.1590/1809-9823.2015.14163
https://doi.org/http://doi.org/10.1590/1...
.

Given the above, the hypothesis of this study was that there is an association among OSA, functional capacity, and metabolic variables in individuals with DM. Therefore, the objective of this study was to verify the association among OSA, functional capacity, and metabolic control variables.

METHODS

This was a cross-sectional, observational, and analytical study developed at the Ceuma University (Street Josué Montello, 1, Jardim Renascença, CEP 65075-120, São Luís, MA, Brazil), with a recruitment period from August 2018 to August 2019 after the study procedures were approved by the Research Ethics Committee of the said institution by means of opinion number 2.469.206. All volunteers included in this study validated their participation by signing the informed consent form.

The inclusion criteria adopted were as follows: individuals of both sexes, with a clinical diagnosis of diabetes mellitus type 2 (T2DM) according to the Brazilian Diabetes Society, and aged ≥18 years. All volunteers were sedentary according to self-report. The exclusion criteria in the present study were as follows: patients with uncontrolled systemic arterial hypertension, amputated diabetes and unable to perform the 2MST, cardiovascular and respiratory diseases limiting their ability to participate in the proposed tests, a clinical diagnosis of neurological diseases, the inability to understand the tests and questionnaires, and any type of medication to sleep.

The assessment consisted of a volunteer identification form, the 2MST, and the Stop-Bang questionnaire88. Duarte RLM, Fonseca LBM, Magalhães-da-Silveira FJ, Silveira EA, Rabahi MG. Validação do questionário STOP-Bang para a identificação de apneia obstrutiva do sono em adultos no Brasil. J Bras Pneumol. 2017;43(6):456-63. https://doi.org/10.1590/s1806-37562017000000139
https://doi.org/https://doi.org/10.1590/...
. In order to assess metabolic control, HbA1c and fasting glucose data were collected from medical records.

The 2MST is calculated by measuring the number of elevations using a knee as a reference. For this study, the number of right knee elevations for 2 min without running was counted and standardized. The minimum knee height, appropriate for the stride, was leveled at a midpoint between the patella and the anterosuperior iliac spine1111. Guedes MBOG, Lopes JM, Andrade AS, Guedes TSR, Ribeiro JM, Cortez LCA. Validation of the two-minute step test for diagnosis of the functional capacity of hypertensive elderly persons. Rev Bras Geriatr Gerontol. 2015;18(4):921-6. http://doi.org/10.1590/1809-9823.2015.14163
https://doi.org/http://doi.org/10.1590/1...
.

During the test, the patient was accompanied by a team member and received support if there was a chance of imbalance. The vital signs were monitored before the start and at the end of the test. The blood pressure (BP) measurement was evaluated using a sphygmomanometer and stethoscope (Premium brand), and the peripheral oxygen saturation (SpO2) and heart rate were measured using an oximeter (MeasuPro model OX150, USA) with a sensor positioned on the index finger and the reading determined after signal stabilization. The chronometer was triggered and interrupted only if the patient requested suspension of test; if indicated by chest pain, intolerable dyspnea, excessive sweating, pallor, dizziness, or cramps; if his/her BP needed to be checked; or if the stipulated time was over. If the patient suddenly interrupted the walk simply to take rest, the timer continued to run. Patients were instructed to wear comfortable clothes and shoes at the time of the test and to take their medications normally.

The Stop-Bang questionnaire consists of a series of eight questions related to snoring, tiredness/fatigue/drowsiness, interrupted breathing during sleep, BP, body mass index, age, neck circumference, and gender, with a total score ranging from 0-8 and answers of only yes or no (scores 1 and 0, respectively). The presence of three or more affirmative responses indicates a high risk for OSA88. Duarte RLM, Fonseca LBM, Magalhães-da-Silveira FJ, Silveira EA, Rabahi MG. Validação do questionário STOP-Bang para a identificação de apneia obstrutiva do sono em adultos no Brasil. J Bras Pneumol. 2017;43(6):456-63. https://doi.org/10.1590/s1806-37562017000000139
https://doi.org/https://doi.org/10.1590/...
.

Statistical analysis

Descriptive analysis was performed and presented with the minimum, maximum, average, and standard deviation values. In addition, to verify the association between the risk of developing OSA with the other variables evaluated, logistic regression was used with the following independent variables: 2MST, HbA1c, blood glucose, and chronicity of T2DM. The association values were presented through the odds ratio (OR) and 95% confidence interval (CI). The risk of developing OSA, assessed using the Stop-Bang questionnaire, was categorized as follows: patients with intermediate and high risk were grouped in the high risk group (n=74) and patients with low risk were grouped in the low risk group (n=26). All data were analyzed using SPSS software (version 17.0; Chicago, IL, USA) at a significance level of 5%.

RESULTS

A total of 160 patients with T2DM were initially recruited at a secondary health care center for patients with T2DM. However, after applying the eligibility criteria, 60 patients were excluded, leaving a final sample containing 100 individuals with T2DM, of whom 61% were women.

According to the Stop-Bang instrument, 26, 57, and 17% of patients had low, intermediate, and high risk of developing OSA, respectively. Other clinical data of the study participants are described in Table 1.

Table 1.
Characteristics of the participants with diabetes mellitus type 2.

When verifying the association between the risk of developing OSA and the other variables, it was observed that the logistic regression model that used the Stop-Bang questionnaire presented adequate modeling (overall=72.7%; Hosmer and Lemeshow test, p=0.867; Nagelkerke R2=0.050). Table 2 presents the OR values, and no significance was identified (p>0.05).

Table 2.
Association between the risk of developing obstructive sleep apnea according to the Stop-Bang and the metabolic control and functional capacity of patients with diabetes mellitus type 2.

DISCUSSION

The main findings of this study were as follows:

  1. there was no association between OSA and functional capacity measured by means of 2MST and

  2. there was no association between OSA and metabolic variables.

Although different methodologies, in agreement with a study by Nisar et al. evaluated on 1,533 individuals, assessed the presence of OSA by polysomnography and the functional capacity by exercise stress echocardiogram, only 404 showed impaired functional capacity. In addition, another recent study highlights the impact of OSA on cardiorespiratory fitness1212. Nisar SA, Muppidi R, Duggal S, Hernandez AV, Kalahasti V, et al. Impaired functional capacity predicts mortality in patients with obstructive sleep apnea. Annals of the American Thoracic Society. 2014 ;11(7):1056-63. https://doi.org/10.1513/AnnalsATS.201309-315OC
https://doi.org/https://doi.org/10.1513/...
.

Recently, a study conducted by Nogueira et al. with the objective of evaluating the reliability of 2MST in healthy individuals concluded that it is a reliable test and still has slight precision in differentiating active and sedentary individuals. The assessment of functional capacity by rapid, simple, and low-cost tests in this population is relevant in view of the need to identify functional limitations due to the disease. In addition, this assessment using this test can and should be used as a method to assess the effectiveness of the proposed treatments1313. Nogueira MA, Almeida TDN, Andrade GS, Ribeiro AS, Rêgo AS, Dias RDS, et al. Reliability and accuracy of 2-minute step test in active and sedentary lean adults. J Manipulative Physiol Ther. 2021:44(2):120-7. https://doi.org/10.1016/j.jmpt.2020.07.013
https://doi.org/https://doi.org/10.1016/...
.

Although OSA was not associated with metabolic variables, it is known that patients affected with this disorder have higher fasting blood glucose levels and high plasma insulin levels, regardless of obesity1414. Qian y, Xu H, Wang Y, Yi H, Guan J, Yin S. Obstructive sleep apnea predicts risk of metabolic syndrome independently of obesity: a meta-analysis. Arch Med Sci. 2016;12(5):1077-87. https://doi.org/10.5114/aoms.2016.61914
https://doi.org/https://doi.org/10.5114/...
. In addition, there is an evidence that sleep deprivation is associated with higher glucose levels, development of insulin resistance, and pancreatic beta cell dysfunction, which is justified despite chronic hypoxemia, increased sympathetic nervous system activity, and increased circulating cortisol intermittent observed in individuals with OSA, culminating in a change in the homeostasis of this variable1515. Punjabi NM, Breamer BA. Alterations in glucose disposal in sleep-disordered breathing. Am J Respir Crit Care Med. 2009;179(3):235-40. https://doi.org/10.1164/rccm.200809-1392oc
https://doi.org/https://doi.org/10.1164/...
,1616. Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62(7):569-76. https://doi.org/10.1016/j.jacc.2013.05.045
https://doi.org/https://doi.org/10.1016/...
,1717. Song SO, He K, Narla RR, Kang HG, Ryu HU, Boyko EJ. Metabolic consequences of obstructive sleep apnea especially pertaining to diabetes mellitus and insulin sensitivity. Diabetes Metab J. 2019;43(2):144-55. https://doi.org/10.4093/dmj.2018.0256
https://doi.org/https://doi.org/10.4093/...
. The non-association between OSA and the metabolic variables found in this study may be possibly justified by the discrepancy in the time of diagnosis of DM, as well as by the control and/or lack of metabolic control found in the population in question.

Regarding the possible clinical implications, based on the previous literature and the results of the present study, OSA should be considered as a secondary factor that implies the functional capacity in diabetic patients along with other factors such as diabetic neuropathy and/or cardiovascular autonomic neuropathy. However, longitudinal studies on this topic are needed to support this clinical implication.

This study has some limitations that should be mentioned. There was an important variation in the time since a diagnosis of T2DM; however, it is worth mentioning that although the medical diagnosis was made within this period of time, it is believed that the metabolic disorder existed for a longer time. Furthermore, peripheral neuropathy was not assessed according to the gold standard1818. Young MJ, Breddy JL, Veves A, Boulton AJ. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. A prospective study. Diabetes Care. 1994;17(6):557-60. https://doi.org/10.2337/diacare.17.6.557
https://doi.org/https://doi.org/10.2337/...
, but all patients were asked about any difficulty in walking or lack of sensitivity in the metatarsals and feet as a whole.

CONCLUSIONS

We concluded that there is no association among OSA measured by means of Stop-Bang instrument, functional capacity measured by means of 2MST, and metabolic variables in individuals with T2DM.

REFERENCES

  • 1
    Garvey JF, Pengo MF, Drakatos P, Kent BD. Epidemiological aspects of obstructive sleep apnea. J Thorac Dis. 2015;7(5):920-9. https://doi.org/10.3978/j.issn.2072-1439.2015.04.52
    » https://doi.org/https://doi.org/10.3978/j.issn.2072-1439.2015.04.52
  • 2
    Foroughi M, Razavi H, Malekmohammad M, Naghan PA, Jamaati H. Diagnosis of obstructive sleep apnea syndrome in adults: a brief review of existing data for practice in Iran. Tanaffos. 2016;15(2):70-4. PMID: 27904537
  • 3
    Spiegel K, Leproult E, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435-9. https://doi.org/10.1016/s0140-6736(99)01376-8
    » https://doi.org/https://doi.org/10.1016/s0140-6736(99)01376-8
  • 4
    Donga E, van Dijk M, van Dijk JG, Biermasz NR, Lammers GJ, van Kralingen K, et al. Partial sleep restriction decreases insulin sensitivity in type 1 diabetes. Diabetes Care. 2010;33(7):1573-7. https://doi.org/10.2337/dc09-2317
    » https://doi.org/https://doi.org/10.2337/dc09-2317
  • 5
    Buxton OM, Pavlova M, Reid EW, Wang W, Simonson DC, Adler GK. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes. 2010;59(9):2126-33. https://doi.org/10.2337/db09-0699
    » https://doi.org/https://doi.org/10.2337/db09-0699
  • 6
    Doumit J, Prasad B. Sleep apnea in type 2 diabetes. Diabetes Spectr. 2016;29(1):14-9. https://doi.org/10.2337/diaspect.29.1.14
    » https://doi.org/https://doi.org/10.2337/diaspect.29.1.14
  • 7
    Hayashino Y, Yamazaki S, Nakayama T, Sokejima S, Fukuhara S. Relationship between diabetes mellitus and excessive sleepiness during driving. Exp Clin Endocrinol Diabetes. 2008;116(1):1-5. https://doi.org/10.1055/s-2007-984442
    » https://doi.org/https://doi.org/10.1055/s-2007-984442
  • 8
    Duarte RLM, Fonseca LBM, Magalhães-da-Silveira FJ, Silveira EA, Rabahi MG. Validação do questionário STOP-Bang para a identificação de apneia obstrutiva do sono em adultos no Brasil. J Bras Pneumol. 2017;43(6):456-63. https://doi.org/10.1590/s1806-37562017000000139
    » https://doi.org/https://doi.org/10.1590/s1806-37562017000000139
  • 9
    Mendelson M, Bailly S, Marillier M, Flore P, Borel JC, Vivodtzev I, et al. Obstructive sleep apnea syndrome, objectively measured physical activity and exercise training interventions: a systematic review and meta-analysis. Front Neurol. 2018;9:73. https://doi.org/10.3389/fneur.2018.00073
    » https://doi.org/https://doi.org/10.3389/fneur.2018.00073
  • 10
    Ben Saad H, Ben Hassen I, Ghannouchi I, Latiri I, Rouatbi S, Escourrou P, et al. 6-min walk-test data in severe obstructive-sleep-apnea-hypopnea-syndrome (OSAHS) under continuous-positive-airway-pressure (CPAP) Treatment. Respir Med. 2015;109(5):642-655. https://doi.org/10.1016/j.rmed.2015.03.001
    » https://doi.org/https://doi.org/10.1016/j.rmed.2015.03.001
  • 11
    Guedes MBOG, Lopes JM, Andrade AS, Guedes TSR, Ribeiro JM, Cortez LCA. Validation of the two-minute step test for diagnosis of the functional capacity of hypertensive elderly persons. Rev Bras Geriatr Gerontol. 2015;18(4):921-6. http://doi.org/10.1590/1809-9823.2015.14163
    » https://doi.org/http://doi.org/10.1590/1809-9823.2015.14163
  • 12
    Nisar SA, Muppidi R, Duggal S, Hernandez AV, Kalahasti V, et al. Impaired functional capacity predicts mortality in patients with obstructive sleep apnea. Annals of the American Thoracic Society. 2014 ;11(7):1056-63. https://doi.org/10.1513/AnnalsATS.201309-315OC
    » https://doi.org/https://doi.org/10.1513/AnnalsATS.201309-315OC
  • 13
    Nogueira MA, Almeida TDN, Andrade GS, Ribeiro AS, Rêgo AS, Dias RDS, et al. Reliability and accuracy of 2-minute step test in active and sedentary lean adults. J Manipulative Physiol Ther. 2021:44(2):120-7. https://doi.org/10.1016/j.jmpt.2020.07.013
    » https://doi.org/https://doi.org/10.1016/j.jmpt.2020.07.013
  • 14
    Qian y, Xu H, Wang Y, Yi H, Guan J, Yin S. Obstructive sleep apnea predicts risk of metabolic syndrome independently of obesity: a meta-analysis. Arch Med Sci. 2016;12(5):1077-87. https://doi.org/10.5114/aoms.2016.61914
    » https://doi.org/https://doi.org/10.5114/aoms.2016.61914
  • 15
    Punjabi NM, Breamer BA. Alterations in glucose disposal in sleep-disordered breathing. Am J Respir Crit Care Med. 2009;179(3):235-40. https://doi.org/10.1164/rccm.200809-1392oc
    » https://doi.org/https://doi.org/10.1164/rccm.200809-1392oc
  • 16
    Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62(7):569-76. https://doi.org/10.1016/j.jacc.2013.05.045
    » https://doi.org/https://doi.org/10.1016/j.jacc.2013.05.045
  • 17
    Song SO, He K, Narla RR, Kang HG, Ryu HU, Boyko EJ. Metabolic consequences of obstructive sleep apnea especially pertaining to diabetes mellitus and insulin sensitivity. Diabetes Metab J. 2019;43(2):144-55. https://doi.org/10.4093/dmj.2018.0256
    » https://doi.org/https://doi.org/10.4093/dmj.2018.0256
  • 18
    Young MJ, Breddy JL, Veves A, Boulton AJ. The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. A prospective study. Diabetes Care. 1994;17(6):557-60. https://doi.org/10.2337/diacare.17.6.557
    » https://doi.org/https://doi.org/10.2337/diacare.17.6.557
  • Funding: none

Publication Dates

  • Publication in this collection
    15 Oct 2021
  • Date of issue
    June 2021

History

  • Received
    24 Apr 2021
  • Accepted
    02 May 2021
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