The Restless Legs Syndrome–Diabetes Link

March 20, 2014

In a US study, diabetes was shown to significantly increase the odds of having restless legs syndrome and a history of diabetes was the most consistent risk factor linked to the disorder.

Restless leg syndrome (RLS) is a movement disorder that affects up to 10% of the US population, tends to worsen with age, and affects women twice as often as men.1 About 85% of patients with RLS also have periodic leg movements of sleep, or foot dorsiflexion that occurs throughout sleep and is accompanied by an autonomic surge and increased blood pressure.2 RLS is associated with many chronic illnesses and so the symptoms are common complaints in primary care practices.

Noteworthy for primary care clinicians who daily see patients from the expanding population of persons with type 2 diabetes mellitus, a strong association has been found between diabetes and the movement disorder. According to a 2013 cross-sectional study of more than 22,000 participants in the US Physicians Health Study I and II, diabetes significantly increased the odds of having RLS (OR = 1.41), and a history of diabetes was the most consistent risk factor linked to RLS.2

RLS Etiology: The Link With Diabetes

Although the cause of RLS has yet to be determined, the disorder is often split into primary and secondary. Primary RLS may have a genetic component, especially among patients who develop RLS before age 40. Basal ganglia dysfunction and disruption of dopamine circuits may also be involved. Parkinson patients with basal ganglia dysfunction and abnormal dopamine levels often have RLS.

Secondary RLS may result from a number of underlying conditions. Some may not be directly related to diabetes, such as lung disease, immune disorders, pregnancy, and adverse effects of certain medications (see below). There is considerable overlap, however, between RLS and diabetes, especially among comorbidities that commonly result from long-standing, poorly controlled hyperglycemia. The observed link between RLS and underlying disease has focused attention on RLS as a potential screening tool for more serious disorders.3

Diabetes comorbidities commonly associated with RLS include2,4,5:

• Neuropathy: possibly one of the main risk factors for RLS

• Cardiovascular disease, hypertension, stroke

• Chronic kidney disease and dialysis

• Obesity

• Deficiency states: iron, vitamin B12, magnesium

• Vascular disease

Associated Health Risks

RLS has been linked to a series of health consequences that negatively impact quality of life. These include5-7:

Sleep disturbance: perhaps one of the most destructive symptoms of RLS; up to two-thirds of RLS patients have serious insomnia and wake up periodically throughout the night, resulting in daytime sleepiness and decreased productivity.5 In turn, RLS symptoms can be exacerbated by sleep deprivation.

Mental health: depression, anxiety

Increased mortality: higher mortality rates have been found among RLS patients, perhaps related to serious underlying comorbidities.

Decreased quality of life: RLS has been linked to worse quality of life than is found in many other chronic conditions, such as osteoarthritis.

Increased health care costs: related to more frequent doctor visits and increased health care utilization.

Diagnosis: RLS or Something Else?

Although the International Restless Legs Syndrome Study Group has defined diagnostic criteria for RLS, there is still no specific test for the disorder. Blood tests can identify deficiency states, and polysomnography can rule out other sleep disorders, such as sleep apnea. In general, the 4 main diagnostic criteria rely on patient history:

• Worsening nighttime symptoms that improve by morning

• An overwhelming urge to move the lower limb(s), usually associated with paresthesias or dysesthesias

• Symptoms are triggered by rest, relaxation, or sleep

• Symptoms are relieved with movement; relief persists as long as movement continues

Management

Optimal control of underlying disease: adequate glycemic control, in the case of diabetes

Correct deficiency states: iron, vitamin B12, or magnesium supplementation

Dopamine agonists: long-term use can worsen symptoms over time; FDA-approved medications for moderate to severe RLS: ropinirole, pramipexole, and rotigotine; carbidopa/levodopa has also been reported to improve symptoms.1 Avoid cabergoline unless the benefits clearly outweigh the risks, because of safety concerns.8

Anticonvulsants: gabapentin, gabapentin-enacarbil, pregabalin

Presynaptic alpha2-adrenergic agonists: clonidine

Benzodiazepines, opioids: use may be limited by daytime sleepiness, potential for abuse or addiction

Nonpharmacologic treatment: smoking cessation; improved sleep hygiene; avoidance of caffeine, alcohol, and nicotine; moderate exercise; hot or cold bath; limb massage; and vibratory or electrical stimulation of affected limbs at bedtime

Avoid medications known to exacerbate symptoms: selective serotonin reuptake inhibitors, serotonin-norepinepherine reuptake inhibitors, lithium, tricyclic antidepressants, dopamine antagonists, some antipsychotics (haloperidol or phenothiazine derivatives), beta-blockers, antinausea drugs (prochlorperazine or metoclopramide), diphenhydramine, and antihistamines.

Conclusion

Since the consequences of RLS can affect nighttime rest and mental health, the disorder can complicate diabetes management.5 Maintaining adequate glycemic control and avoiding medications that can exacerbate symptoms are two strategies that can help relieve the distress of RLS as well as minimize development of diabetic comorbidities. Conversely, symptoms of RLS in your patients, particularly those with diabetes who may be at increased risk for the disorder, could be one way of monitoring for worsening diabetes complications.   

References:

1. NIH Restless Legs Syndrome Fact Sheet. http://www.ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm. Accessed March 14, 2014.

2. Winter AC, Berger K, Glynn RJ, et al. Vascular risk factors, cardiovascular disease and restless legs syndrome in men. Am J Med. 2013;126:228-235.e2. doi:10.1016/j.amjmed.2012.06.039.

3. Zhang C, Li Y, Malhotra A, et al. Restless legs syndrome status as a predictor for lower physical function. Neurology. Published online ahead of pint March 5, 2014. doi:10.1212/WNL.0000000000000284.   

4. Ekbom K, Ulfberg J. Restless legs syndrome. J Intern Med. 2009;266:419-431.

5. Merlino G, Valente M, Serafini A, et al. Effects of restless legs syndrome on quality of life and psychological status in patients with type 2 diabetes. Diabetes Educ. 2010;36:79-87. doi:10.1177/0145721709351252. 

6. Salas RE, Kwan AB. The real burden of restless legs syndrome: clinical and economic outcomes. Am J Manag Care. 2012;18:S207-S212.

7. Li Y, Wang W, Winkelman JW, et al. Prospective study of restless legs syndrome and mortality among men. Neurology. 2013;81:52-59. doi:10.1212/WNL.0b013e318297eee0. Epub 2013 Jun 12.

8. Garcia-Borreguero D, Kohnen R, Silber MH, et al. The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. Sleep Med. 2013;14:675-684.