Sleep Disturbances: Type 2 Diabetes Risk?

Sleep disturbances commonly co-occur with diabetes, negatively impacting quality of life and work productivity. According to a recent CDC study, people with diabetes have a higher likelihood of having sleep problems than those without diabetes.¹

However, a bidirectional relationship exists between sleep disturbances and diabetes, producing a chicken-or-egg scenario: Do sleep disturbances predispose to worsening glycemic control, or vice versa?

On the one hand, conditions related to diabetes, like nocturia, nocturnal hypoglycemia, peripheral neuropathy, restless leg syndrome, and sleep disordered breathing may all contribute to sleep disorders in those with diabetes.² Poor sleep may also contribute to suboptimal diabetes care, including medication nonadherence, lack of exercise, and an unhealthy diet.³

On the other hand, sleep problems have been implicated in the development of T2DM, worse glucose control in those who already have diabetes, and increased risk of diabetic complications.^4,5

A recent systematic review and meta-analysis covering 36 studies and over one million individuals found that sleep disorders conferred a similar risk for diabetes as traditional risk factors, such as family history and sedentary behavior. Moreover, obstructive sleep apnea (OSA) as well as difficulty initiating and maintaining sleep had an even larger effect on diabetes risk than physical inactivity.⁶

Large, prospective studies have shown a U-shaped relationship between sleep duration and risk for T2DM, with both longer and shorter sleep duration linked to increased HbA1c levels. Smaller, cross-sectional studies have also linked sleep duration to the development of insulin resistance and T2DM.^3,5,7

Experimental studies in animals and humans have linked sleep disturbances to decreased beta cell responsiveness, decreased insulin sensitivity, and/or decreased glucose effectiveness.^4,6 For example, in a recent randomized study of 14 individuals who underwent sleep restriction to four hours per night for five nights in a sleep lab, whole body insulin sensitivity significantly decreased by 25%, peripheral insulin sensitivity decreased by 29%, and stress hormones modestly increased, compared to participants who slept 8 hours per night.⁸ Whether or not extending sleep can improve glucose control and insulin sensitivity is an open question, but recent research suggests a beneficial effect for sleep extension.⁵

Several mechanisms may play a role in the association between sleep disturbances and diabetes. Increased sympathetic nervous system activity, increased evening cortisol levels, growth hormone suppression, disruption of the circadian rhythm, and increased systemic inflammation may all contribute.^9,10 Sleep disturbances may also be accompanied by decreased levels of the appetite-regulating hormone leptin, which may increase cravings for carbohydrate-dense foods and sweets.⁴ Changes in leptin levels, leptin resistance, and HPA axis dysregulation³ as well as increased levels of ghrelin (which increases appetite) may also be involved.¹⁰

Shift Work

Much research surrounds the link between metabolic dysregulation and the bane of modern existence: shift work. For example, one study conducted in female workers in China found that each 10 years of shift work was linked to 10% increased odds of developing metabolic syndrome.¹¹ Night shift work and rotating shift work, in particular, have been linked to higher prevalence of diabetes, with some research suggesting that even slight changes in schedule can play a role in the development of diabetes.⁴

Sleep deprivation, circadian desynchronization, decreased levels of physical activity, and exposure to bright lights may all contribute to the effect of shift work on diabetes risk. Weight gain has also been associated with shift work, and may be related to increased preference for carbohydrates and sugary foods.⁹

OSA

Rates of OSA have skyrocketed in recent decades, which may have consequences for diabetes prevention and control. OSA has been linked to increased odds of T2DM, insulin resistance, and metabolic syndrome, and severe OSA is linked to worse glycemic control in diabetics.^12-14 A recent study of individuals with T2DM found that having severe OSA was associated with an increase in HbA1c of 3.69%, compared to diabetic patients without OSA.¹⁴ While some studies point to a bidirectional relationship,¹² others have suggested that OSA may independently contribute to insulin resistance.¹³

The sleep fragmentation of OSA may negatively impact beta cell function, insulin sensitivity, adipose tissue function, and systemic inflammation. In particular, sympathetic excitation triggered by intermittent hypoxia may lead to catecholamine release, decreased insulin sensitivity, and decreased insulin-mediated glucose uptake. Increased reactive oxygen species (ROS) and oxidative stress may also play a role. Intermittent hypoxia also activates the transcription factor NF-KB, which regulates the inflammatory response and other inflammatory genes like TNFα, IL-8, or intracellular adhesion molecule 1 (ICAM-1).¹³

Whether or not using continuous positive airway pressure (CPAP) improves insulin resistance remains unclear, though. Adherence issues and the difficulty of devising a sham CPAP device may contribute to conflicting research results. A recent review, however, has found that the benefits of CPAP may be greater in those with more severe OSA, poor baseline glycemic control, and greater compliance with CPAP treatment.¹⁵

Overall, research seems to point to sleep disturbances as an under-recognized yet potentially modifiable factor in diabetes prevention and management. Yet organizations like the American Diabetes Association, the International Diabetes Federation, and the Centers for Disease Prevention do not include sleep problems in their screening recommendations for T2DM. Which raises an important question: should they? 

Take-home Points

• Sleep disturbances commonly co-occur with diabetes, negatively impacting quality of life and work productivity.

• A bidirectional relationship exists between sleep disturbances and diabetes: conditions related to diabetes may contribute to sleep disorders in those with diabetes, while meta-analyses, prospective, cross-sectional, animal, and human experimental studies have implicated sleep disturbances in the development of T2DM, worse glucose control in those who already have diabetes, and increased risk of diabetic complications.  

• Shift work and obstructive sleep apnea represent two major issues that contribute to the link between sleep disturbances and diabetes risk.

• Research points to sleep disturbances as an under-recognized yet potentially modifiable factor in diabetes prevention and management, which raises the question of whether sleep disturbance should be included in T2DM screening recommendations.

References:

1. Plantinga L, et al. Prevalence of self-reported sleep problems among people with diabetes in the United States, 2005-2008. Prev Chronic Dis. 2012;9:E76.

2. Surani S, et al. Effect of diabetes mellitus on sleep quality. World J Diabetes. 2015 Jun 25;6(6):868-873.

3. Lee SW, et al. The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: a systematic review and meta-analysis. Sleep Med Rev. 2016 Feb 9.

4. Arora T, Taheri S. Sleep optimization and diabetes control: a review of the literature. Diabetes Ther. 2015 Dec;6(4):425-468.

5. Alnaji A, et al. The role of sleep duration in diabetes and glucose control. Proc Nutr Soc. 2016 Jun 23:1-9.

6. Anothaisintawee T, et al. Sleep disturbances compared to traditional risk factors for diabetes development: systematic review and meta-analysis. Sleep Med Rev. 2015 Oct 21;30:11-24.

7. Gottlieb DJ, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863-867.

8. Rao MN, et al. Subchronic sleep restriction causes tissue-specific insulin resistance. J Clin Endocrinol Metab. 2015 Apr;100(4):1664-1671.

9. Brum MC, et al. Shift work and its association with metabolic disorders. Diabetol Metab Syndr. 2015 May 17;7:45.

10. Reutrakul S, Van Cauter E. Interactions between sleep, circadian function, and glucose metabolism: implications for risk and severity of diabetes. Ann N Y Acad Sci. 2014;1311:151-117. 

11. Guo Y, et al. Shift work and the relationship with metabolic syndrome in Chinese aged workers. In: Behrens T, et al., editors. PLoS One. 2015 Mar 11;10(3):e0120632.

12. Rajan P, Greenberg H. Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus. Nat Sci Sleep. 2015 Oct 5;7:113-125.

13. Kent BD, et al. Insulin resistance, glucose intolerance and diabetes mellitus in obstructive sleep apnoea. J Thorac Dis. 2015 Aug;7(8):1343-1357.

14. Aronsohn RS, et al. Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med. 2010;181:507-513.

15. Martínez-Ceron E, et al. Effects of continuous positive airway pressure treatment on glucose metabolism in patients with obstructive sleep apnea. Sleep Med Rev. 2016 Feb;25:121-130.