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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 30-34

Sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among diabetic foot patients


Vascular Surgery Department, Xuan Wu Hospital of Capital Medical Unverisity, 100053, Beijing, China

Date of Web Publication10-Jul-2018

Correspondence Address:
Lianrui Guo
Department of Vascular Surgery, Xuanwu hospital of the Capital Medical University, 100053, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/VIT.VIT_2_18

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  Abstract 

CONTEXT: Sleep disturbance and proinflammatory markers were reported to link to the development of type 2 diabetes mellitus and glucose homeostasis.
METHODS: A clinical laboratory–based analysis was performed on 14 normal volunteers, 11 diabetic patients and 16 non-diabetic patients form department of vascular surgery conducted between January 2013 and March 2013. Continuous polysomnographic monitoring was performed on 2 nights in the intensive care unit (IUC). Blood glucose level was controlled by insulin infusion. Concentrations of IL-6 and CRP levels were determined by enzyme-linked immunoassays.
OBJECTIVE: To raise awareness of risk factors among postsurgery type 2 diabetes with foot ulcers.
DESIGN: A clinical laboratory-based analysis was performed on 14 normal volunteers, 11 diabetic patients, and 16 nondiabetic patients from Department of Vascular Surgery conducted between January 2013 and March 2013.
SETTING: This trial was admitted to Siping hospital affiliated to China Medical University, China.
PATIENTS: Twenty-seven patients were postthrombolytic therapy and 14 healthy controls.
INTERVENTIONS: Continuous polysomnographic monitoring was performed on 2 nights in the Intensive Care Unit (ICU). Blood glucose level was controlled by insulin infusion. Concentrations of interleukin-6 (IL-6) and C-reactive protein (CRP) levels were determined by enzyme-linked immunoassays.
MAIN OUTCOME MEASURE: Changes in exogenous insulin requirements, while IL-6 and CRP levels.
RESULTS: Insulin requirements on admission in ICU 48-h treatment increased 21.2% in diabetic patients compared to 24-h postsurgery. All postsurgical patients elevated IL-6 and CRP levels compared to normal individuals in the morning after 24 h and 48 h of sleep restriction. Fasting concentrations of IL-6 were distinctly increased 23.6% and 42.9%, respectively, after 24 h and 48 h of sleep restriction in diabetic patients compared to normal individuals and 18.5% and 21.8%, respectively, compared to nondiabetic patients. CRP levels are similar to IL-6 levels among these partners.
CONCLUSIONS: Our study elucidated that sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among postsurgical diabetic patients, which might contribute to understand these disorders for diabetic patients in immunological pathways.

Keywords: C-reactive protein, glucoregulatory, interleukin-6, sleep disruption, type 2 diabetes mellitus


How to cite this article:
Ye C, Li H, Tong Z, Qi L, Guo L. Sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among diabetic foot patients. Vasc Invest Ther 2018;1:30-4

How to cite this URL:
Ye C, Li H, Tong Z, Qi L, Guo L. Sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among diabetic foot patients. Vasc Invest Ther [serial online] 2018 [cited 2018 Jul 19];1:30-4. Available from: http://www.vitonline.org/text.asp?2018/1/1/30/236292


  Introduction Top


Several studies have examined the association between sleep duration, sleep disturbance, and the development of type 2 diabetes mellitus.[1],[2],[3] The mechanism involved in impaired glucose metabolism following changes in the sleep-wake rhythm seems to be a decreased efficacy of the negative-feedback regulation of the hypothalamus-pituitary-adrenal axis.[4] Moreover, alterations in endocrine stress systems,[5] and proinflammatory markers of the immune system [6] are tightly linked to the regulation of glucose homeostasis. It has been shown that interleukin-6 (IL-6) and C-reactive protein (CRP) are increased in individuals who are insulin resistant and obese, and these biomarkers predict the development of type 2 diabetes.[7],[8] Furthermore, stress due to sleep deprivation affects inflammatory markers, linking sleep debt and insulin resistance.[9] However, until now, experimental evidence for a causal link between sleep loss and impairments of glucose metabolism in postsurgery patients has been scarce.

Here, we assessed the effects of moderate sleep restriction to 4 h for 2 consecutive days among diabetic and nondiabetic patients postsurgery comparison to normal individuals on glucose. We also observed the relevant parameters of circulating concentrations of IL-6 and CRP. The purposes of our study are to raise awareness of the potential of risk factors during the process of type 2 diabetes postsurgery in Intensive Care Unit (ICU) and to report our clinical experience.


  Methods Top


Study sample

The current report involves 14 normal volunteers, 11 diabetic foot patients, and 16 nondiabetic patients form Department of Vascular Surgery participating in a clinical laboratory-based examination conducted between January 2016 and March 2016. All the patients received thrombolytic therapy.

Normal volunteers were recruited from the general community. To participate, volunteers who were medically healthy, as determined by medical history, physical examination, and laboratory testing were recruited. They had to be <60 years in age, have a body mass index, 30 kg/m 2, consume <2 alcoholic or three caffeinated beverages per day, habitually sleep for at least 7 h/night, have a usual bedtime before midnight, and not work at night or on a rotating shift schedule.[10] After an initial telephone screening, eligible volunteers were required to complete a serologic screen and an overnight polysomnogram to rule out obstructive sleep apnea, as previously described.[10],[11] Usual sleep habits were also objectively assessed with a wrist activity monitor that was worn for at least 5 days, including 1 weekend. A normal polysomnogram, a demonstration of habitual bedtime by midnight, and an average of at least 7 h of sleep on actigraphy were required for enrollment.

After enrollment, multiple contacts were made to counsel each volunteer on maintaining at least 7 h of sleep per night. Ambulatory monitoring of sleep habits was repeated for three nights before the baseline metabolic evaluation to confirm that habitual sleep patterns remain unchanged. Volunteers were excluded from participating in the study if sleep duration on any night was <6 h or the average sleep duration was <7 h preceding admission to the clinical research unit (CRU). Female volunteers were scheduled for the study protocol during the follicular phase (days 4–10) of the menstrual cycle. Dietary records were collected from all volunteers for 3 days before the study to assess the average daily intake of carbohydrates, protein, and fat from any source (e.g. fruits and vegetables), as instructed by a certified dietician. Informed consent was obtained from each volunteer, and the study protocol was approved by Siping hospital affiliated to China Medical University.

After All, there were 11 diabetic patients and 16 nondiabetic patients were involved.

Study protocol

[Figure 1] displays the timeline for the study protocol. Each eligible participant was admitted to the CRU (8:00 am) after an overnight fast. One night of uninterrupted and two nights of fragmented sleep then followed. Venous blood samples were obtained at 7:30 am on the day of admission and after two nights of sleep fragmentation. After centrifuging and aliquoting by using standardized protocols, samples were stored at −80°C until assayed.
Figure 1: Study protocol timeline. Each eligible participant was admitted to the CRU (8:00 am) after an overnight fast. One night of uninterrupted and two nights of fragmented sleep then followed. Venous blood samples were obtained at 7:30 am on the day of admission and after two nights of sleep fragmentation

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Sleep fragmentation

Continuous polysomnographic monitoring was performed on each of the 2 nights in the CRU. Lights out and morning wake times for each individual were matched to their usual bedtimes and wake times and kept constant throughout the 2-night CRU stay. During the day, individuals were ambulatory in the CRU but were not allowed to sleep.

Normal individuals were instructed to eat a light dinner before arrival at the research unit at 20:00 each laboratory night. Thereafter, they were only allowed to drink water until the next morning. After preparation of polysomnographic recordings, individuals went to bed and lights were turned off at 22:45 in the 8-h sleep condition. In the 4-h sleep condition, individuals remained awake in a sitting position until 02:45. They were allowed to read and to watch nonarousing movies. Brisk physical activities were avoided and individuals were constantly monitored by the experimenters. After each experimental night in both conditions, individuals were woken up at 07:00.

Insulin protocol and blood glucose measurements

All partners use insulin infusion to control blood sugar at 110–200 mg/ml. Blood glucose (BG) measurements are scheduled every 2 h by registered nurses using the SureStep ®(OneTouch ®) Professional BG Monitoring System (Lifescan, Inc., Milpitas, CA). It uses a modification to a protocol published by White et al.[12] and Bode et al.[13] with dose computed according to the following formula:

Insulin dose (units/h) = (multiplier) × (Blood glucose [mg/dL] −60)

The multiplier (M) variable is initially set to 0.03 and adapts according to a set protocol although it can never fall below zero. BG values exceeding the high target threshold on two consecutive BG measurements, or exceeding 200 mg/dL on one reading, trigger a multiplier increase of 0.01. BG values below the low target threshold decrease the multiplier by 0.01, and BG values below 60 mg/dL decrease the multiplier by 0.02. When BG values fall below the low target threshold, the protocol orders a calculated dose of intravenous 50% dextrose to correct or prevent hypoglycemia. The intravenous insulin infusion is simultaneously withheld for 2 h. Insulin is dispensed by the pharmacy as 150 units of regular insulin in 150 mL of normal saline (1U/1 mL concentration). BG levels are measured at least every 2 h for patients who are not hypoglycemic and every hour for patients with a recent hypoglycemic episode.

Assay of serum interleukin-6 and C-reactive protein

Venous blood sampling was conducted before the normal individuals and after all partners underwent sleep disruption. The blood collected for IL-6 serum level assessments was collected in plain tubes, and the levels of serum IL-6 were measured using commercially available enzyme-linked immunosorbent assays (Quantikine human IL-6, R and D Systems Inc., Minneapolis, USA); high sensitivity CRP assays were obtained from ALPCO Diagnostics (Salem, NH). The blood samples were centrifuged for 10 min at 3000 r/min at 4°C. The serum was subsequently removed and stored at −80°C until biochemical analysis. All samples were run as duplicates, and the mean values were reported.

Statistical analysis

All data are expressed as mean ± standard deviation. The Student's t-test was used to evaluate the statistical significance of differences between means. P 0.05 was considered as statistically significant.


  Results Top


Patient clinical data

As shown in [Table 1], there is no significant difference among partners.
Table 1: Clinical characteristics on all partners (Mean±SD)

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Glucose metabolism before and after sleep disruption

There was no hypoglycemia onset in the current study; only 2 nonpatients used insulin infusion to control blood sugar. As seen in [Table 2], fasting plasma glucose level analyses revealed that there was no effect of sleep deprivation among normal individuals before and after sleep disruption, while insulin requirements on admission in ICU 48-h treatment increased 21.2% in diabetic patients compares to 24-h postsurgery. These results indicated a pronounced effect of sleep loss on glucose metabolism.
Table 2: Clinical characteristics on blood glucose values and insulin requirements during treatment

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Interleukin-6 and C-reactive protein levels

All patients postsurgery had elevated IL-6 and CRP levels compared to normal individuals in the morning after 24 and 48 h of sleep restriction. Fasting concentrations of IL-6 were slightly elevated 5.6% and 11.2%, respectively, after 24 and 48 h of sleep restriction among normal individuals compared to pretreatment. Fasting concentrations of IL-6 were distinctly increased 23.6% and 42.9%, respectively (*P < 0.05), after 24 and 48 h of sleep restriction in diabetic patients compared to normal individuals and 18.5% and 21.8%, respectively, compared to nondiabetic patients. CRP levels are similar to IL-6 levels among these partners [Table 3].
Table 3: IL-6 and CRP levels of partners

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  Discussion Top


Our data indicate a distinct reduction in glucose tolerance in conjunction with elevated insulin requirements in response to 2 nights of mild sleep restriction to 4 h in normal individuals, diabetic, and nondiabetic foot patients. This pattern of effects points to reduced insulin sensitivity (i.e., increased insulin resistance). Furthermore, serum IL-6 and CRP concentrations were found be elevated in the morning after 2 nights of mild sleep restriction suggesting a contribution of clinical inflammation.

IL-6 was reported to lead a systemic chronic subinflammatory state during stress and following disturbances of the sleep pattern, which could play a central role in the development of insulin resistance and type 2 diabetes.[14] In this current study, all patients postsurgery had elevated IL-6 levels compared to normal individuals in the morning after 24 and 48 h of sleep restriction; and concentrations of IL-6 were distinctly increased 23.6% and 42.9%, respectively, after 24 and 48 h of sleep restriction in diabetic patients compared to normal individuals and 18.5% and 21.8%, respectively, compared to nondiabetic patients. These results were complied with insulin requirements to control glucose level, suggested increased insulin resistance that links IL-6 level to disturbed glucose metabolism.

CRP is an acute phase protein, which levels raise in response to inflammation. It is a sensitive but nonspecific inflammatory biomarker often used as an indicator for surgery or early postoperative complications.[15] In this current study, all patients postsurgery had distinctly elevated CRP levels compared to normal individuals in the morning after 24 and 48 h of sleep restriction and concentrations of CRP were distinctly increased in diabetic patients compared to nondiabetic patients. These results were also complied with insulin requirements to control glucose level, suggested (i) increased insulin resistance that links CRP level to disturbed glucose metabolism; (ii) a longer acute phase in diabetic patients than nondiabetes; (iii) CRP can be a predictor for clinical deterioration in the surgical critically ill diabetic patient in ICU.

Several studies have argued that sleep loss-associated reductions in insulin sensitivity [16],[17],[18],[19] and glucose tolerance [20] may be due to increased activity of the sympathetic nervous system (SNS), which was not assessed in our study. Further studies are necessary to better elucidate the role of sleep loss in inflammation factors' release, SNS, and their relationships with glucose metabolism, which could be important to control blood sugar among postsurgery diabetic patients.


  Conclusions Top


Our study elucidated that sleep disruption aggravates disturbed glucoregulatory and systemic inflammation among diabetic patients than normal individuals postsurgery, which might contribute to profound implications for an understanding of these disorders for diabetic patients in immunological pathways.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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