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Association Between Poor Sleep Quality and Glycemic Control in Adult Patients with Diabetes Referred to Endocrinology Clinic of Guilan: A Cross-sectional Study

Background Diabetes is a prevalent chronic medical comorbid condition worldwide. Diabetes mellitus is associated with various sleep disorders. Objectives We aimed to determine the prevalence of poor sleep and the main factors of sleep interruptions in patients with diabetes mellitus. We further evaluated the association of sleep interruptions with glycemic control in this cohort. Methods We conducted a cross-sectional study on 266 patients with type 1 and type 2 diabetes recruited from a university outpatient endocrinology clinic. Patients completed a checklist including demographic and disease-related characteristics in addition to the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Using the PSQI cutoff score of 5, we created two subgroups of good sleepers (GS) and poor sleepers (PS). Results Our results showed that good sleeper and poor sleeper patients with diabetes were significantly different regarding sex, employment status, BMI, presence of diabetes-related complications, HbA1c, and 2-hour postprandial blood sugar (2HPPBS) (all significant at P < 0.05). The most prevalent factors of sleep interruptions were “waking up to use a bathroom”, “feeling hot”, “pain”, “having coughs or snores”, and “bad dreams”. Among the subjective factors of sleep interruption, problems with sleep initiation, maintenance, or early morning awakenings in addition to having pain or respiratory problems such as coughing or snoring had the most significant associations with HbA1c. Conclusions Our study showed significant subjective sleep disturbances (both quality and quantity) in patients with diabetes mellitus (both type I and II) and its association with diabetes control. We further identified the main factors that led to sleep interruptions in this cohort.


Background
Diabetes mellitus (DM) is one of the main chronic medical conditions worldwide in all nationalities and social classes (1). In 2017, the International Diabetes Federation reported that 451 million patients had DM, and this will grow to 693 million by 2045 (2). It causes several complications. Among them, sleep disorders have been less noticed (3). During the previous decades, the prevalence of sleep disturbances and deprivation has increased dramatically (4). Ongoing patient self-management education and support are critical for preventing acute and chronic complications in DM (5), but it seems that diabetic patients are less informed about sleep health. Previous studies by Zhu et al. (6) and van Dijk et al. (7) reported poor sleep quality in 47.1% of patients with T2DM and 35.4% in T1DM, respectively.
parasomnias, and sleep-related movement disorders (8). It is noteworthy that the high risk of various diseases such as obesity and Type 2 diabetes mellitus (T2DM) occurs due to impaired sleep quality and quantity (9). Sleep disturbance, insufficient or excessive sleep, and irregular sleepwake patterns have been related to several body dysfunctions such as endocrine system and metabolic health (10) and increased prevalence and incidence of diabetes or the poor glycemic control of diabetic patients (11). Reutrakul et al. reported associations between glycemic control and sleep quality or duration (12). Inadequate sleep and fragmented sleep are both associated with abnormal glucose metabolism and sleep deprivation. Sleep deprivation directly affects glucose tolerance by modulating insulin sensitivity (13,14). Besides, sleep disorders and intermittent hypoxia may affect glucose metabolism in the body (6

Objectives
Our study is novel as it studied both T1DM and T2DM and evaluated the causes of poor sleep in more detail to find an association between poor glycemic control and sleep disorders.

Assessment of Subjective Sleep Characteristics
The pittsburg sleep quality index (PSQI) is a validated A global PSQI score > 5 indicates poor sleep quality, with a satisfactory sensitivity (90%) and specificity (87%) when compared with objective clinical and laboratory measures (15). Thus, those with the PSQI of less than five were considered good sleepers (GS), and those with the PSQI of five or higher were considered poor sleepers (PS).

Statistical Analyses
Data were analyzed using SPSS version 26  and T2DM patients in the report of poor sleep. There was a higher proportion of female patients in the PS group (P = 0.005). Further, the PS group had more housekeepers and fewer students (P = 0.041), higher BMI (P = 0.013), higher prevalence of diabetes-related complications (P < 0.0001), higher HbA1c (P = 0.001), and higher 2-hour postprandial blood sugar (2HPPBS) (P = 0.033). The participants who reported sleep time of fewer than five hours or more than seven hours had significantly higher HbA1c than those who slept 5 -7 hours (P = 0.017). 29.6%, P < 0.0001). The most prevalent causes of sleep interruptions were midnight or early morning awakenings, uncomfortable breathing, waking up to use a bathroom, feeling hot, feeling cold, pain, having cough or snoring, and bad dreams. The odds ratio of less than one shows fewer odds of being characterized as GP. Table 3 shows the association between the subjective causes of sleep interruptions and HbA1c. Problems with sleep initiation, sleep maintenance, and early morning awakenings were associated with higher HbA1c. The participants who responded "yes" to "cannot get to sleep within 30 minutes", had higher HbA1c than those who responded "no" (8.00% vs. 7.41%, P < 0.005). In addition, the participants who responded "yes" to "waking up at night or early morning" had higher HbA1c than those who responded "no" (7.82% vs. 7.49%, P < 0.05). Further, "waking up to use a bathroom", "having pain", and "coughing or snoring loudly" were associated significantly with higher HbA1c (all Pvalues < 0.05).
Linear regression analysis showed that sleep quality was negatively related to HbA1c when adjusted for age, sex, BMI, and DM-related complications (P = 0.003). For patients with the same level of age, sex, BMI, and diabetesrelated complications, the mean HbA1c level was 0.621 (SD = 0.21) units lower in good sleepers than in poor sleepers.

Discussion
We examined the prevalence and causes of sleep inter- health in T2DM (21). Therefore, it is necessary to consider stress in patients with T1DM and T2DM.
The prevalence of poor sleep among the general population of Iran in Tehran was studied in a cross-sectional study in 2012, which reported a 37% prevalence of poor sleep (22). Previous studies (6, 7) reported poor sleep quality in 47.1% of patients with T2DM and 35.4% in T1DM. The prevalence of poor sleep was higher in our cohort, which can be due to the more advanced stage of diabetes in our participants who were referred to an endocrinology clinic.
In addition to causing direct sleep disturbances as a result of nocturia, polyuria, diabetic neuropathy, and neuropathy pain, DM has also been associated with several chronic illnesses like obstructive sleep apnea, cardiovascular complications, hypertension, cerebrovascular accidents, and depression, which can impair sleep and quality of life (23).
Our participants completed the survey at the time of the COVID-19 pandemic, and that may partially explain the higher prevalence of disturbed sleep in our cohort. The COVID-19 pandemic and quarantine and its related conditions may have affected sleep quality, as shown in other reports in which home quarantine due to the COVID-19 pandemic had a detrimental impact on sleep quality (24,25). Additionally, in the current study, we did not compare sleep quality and insulin resistance of DM patients with a control group; however, a similar study by van Dijk et al. considered it. They compared a group of patients with T1DM with a matched non-diabetic control group and reported a higher prevalence of subjective sleep disorders in long-standing T1DM patients than in the control group (7). 4 Int J Endocrinol Metab. 2022; 20(1):e118077.  A similar study on T1DM showed an up to 21% increase in insulin resistance after a single night of sleep restriction (27). Another study on T2DM concluded that patients had a high prevalence of sleep disorders that negatively affected glycemic control (6). These results demonstrated the importance of good sleep quality for insulin resistance and the probable predominant effect of 2HPPBS rather than FBS on HbA1c as the indicator of the mean glycemic control in the last three months. It is noteworthy that using oral agents for controlling blood glucose could mainly affect the glucose levels after eating (2, 3), regarding their potential effects on insulin resistance. Therefore, it seems that the significant relationship between sleep quality and 2HPPBS may indicate the effect of sleep quality on drug efficacy in addition to insulin sensitivity (28,29). To guide these patients to establish a good sleep pattern, we studied the components of the PSQI to address what elements of impaired sleep were more related to poor glycemic control.
Among the components of PSQI, previous studies reported sleep duration, sleep latency (6), and sleep disturbances (6, 7) as associated factors with HbA1c, which is consistent with our findings. Our study uniquely considered the causes of sleep disturbances in more detail. Previous investigations on T1DM noted impaired sleep quality as a result of neuropathic pain (26), night hypoglycemia, and consequently higher carbohydrate use in the morning (27), as well as disrupted sleep and psychological factors (30,31). One of the most considerable factors that caused sleep interruptions was pain probably as a result of neuropathy, which is consistent with previous studies demonstrating the effect of pain on sleep quality (32). Thus, pain control and prevention of diabetic neuropathies in diabetic patients may improve sleep quality and glycemic control. One interesting finding of our study was the higher prevalence of poor sleep quality among female patients.
This finding was compatible with a similar study by Keskin et al. (33).
There were limitations in this study, including being cross-sectional and not having a control group. Besides, the participants were asked to complete an online survey for evaluating their sleep quality. In addition, our study lacked objective sleep-related parameters. Although patients were referred to specific laboratories for checking HbA1c, they used the same kit and method of assessment.
In addition, we cannot neglect the coincidence of performing this study with the COVID-19 pandemic that restricted access to patients and clinicians.

Conclusions
Our data showed significant subjective sleep disturbances (both quality and quantity) in patients with diabetes mellitus (both type I and II) and its association with diabetes control. We further identified the main factors that led to sleep interruptions in this cohort. Poor Int J Endocrinol Metab. 2022; 20(1):e118077. 5 sleep quality is prevalent among both types of diabetic patients, and it is associated with higher HbA1c, 2HPPBS, and poor glycemic control of these patients. We found many sleep-disrupting factors that cause higher HbA1c, including shorter sleep duration, longer sleep latency, midnight and early morning awakenings, waking up to use a bathroom, respiratory problems such as cough or snore loudly, and pain. Proper attention to the sleep quality of diabetic patients and implementing interventions that reduce sleep interruptions may improve diabetes outcomes, besides the effects of well-controlled blood glucose. Funding/Support: No funding was received.
Informed Consent: Written informed consent was obtained from the participants.