Sleep, Diabetes, and Pain: Intricately Intertwined

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LAS VEGAS—Sleep and diabetes, diabetes and pain, and pain and sleep all are intricately intertwined, said Victor Rosenfeld, MD, Medical Director of the Sleep Center at the SouthCoast Medical Group, Savannah, Georgia.

SLEEP AND DIABETES

Sleep and diabetes go hand-in-hand. Diabetes can cause sleep loss, and poor sleep can increase the risk for or worsen diabetes. Tired people eat more sugary foods for energy. Sleep deprivation has been linked with prediabetes.

In addition, said, lack of adequate sleep is related to weight gain, which in turn can worsen sleep, insulin resistance, and glucose tolerance. Weight gain worsens sleep, which worsens weight and diabetic control which worsens weight, which worsens sleep—and so on.

One in 15 people has moderate-to-severe obstructive sleep apnea (OSA) and, among the middle-aged working population, this increases to 9% in women and 24% in men. One study found 97% of those who were both obese and had diabetes suffered from OSA, which may also have a causal role in the development of diabetes. Approximately 85% of those with OSA have not been diagnosed, he said.

OSA is associated with insulin resistance (independent of obesity), and 30% of patients presenting to a sleep clinic have impaired glucose tolerance or diabetes, of which 40% are undiagnosed. Many possible mechanisms have been proposed, from intermittent hypoxia to an increase in cortisol, glucagon, and glucocorticoids, he said. Use of continuous positive airway pressure (CPAP) may improve insulin sensitivity.

DIABETES AND PAIN

Many patients with diabetic neuropathy have no symptoms, while others have pain, tingling, or numbness. Diabetic neuropathy can affect every organ system. Although 60% to 70% of patients with diabetes have some form of neuropathy, the highest rates are in those with diabetes for more than 25 years, Dr. Rosenfeld said.

The causes of diabetic neuropathy include metabolic factors, neurovascular damage, autoimmune factors, mechanical injuries, and lifestyle factors. Mechanisms include polyol pathway activation, protein kinase C activation, oxidative stress, poly (ADP-ribose) polymerase activation, alteration in neurotrophic factors, advanced glycation end product formation, and essential fatty acid abnormalities.

Types of diabetic neuropathy include peripheral, autonomic, proximal, and focal. Large fiber peripheral neuropathy can be assessed by NCS/EMG studies, while small fiber peripheral neuropathy, which cannot be seen on NCS/EMG, can now be identified by skin punch biopsy.

Tight glucose control and alpha-lipoic acid (100 mg twice daily) can possibly help prevent progression of diabetic neuropathy, he said. Medications include the tricyclics (amitriptyline, nortriptyline, imipramine), the serotonin–norepinephrine reuptake inhibitors (duloxetine and venlafaxine), the anticonvulsants (gabapentin, pregabalin, carbamazepine), and opioids (oxycodone and tramadol). The US Food and Drug Administration has specifically approved duloxetine and pregabalin for the treatment of painful diabetic peripheral neuropathy.

The advantages of duloxetine, Dr. Rosenfeld said, are that it is well tolerated and efficacious; disadvantages are that it takes a few weeks to work, with side effects including nausea, constipation, diarrhea, dry mouth, fatigue, somnolence, and dizziness. Pregabalin also improves sleep; side effects of pregabalin include edema, dizziness, sleepiness, confusion, blurred vision, and weight gain.

PAIN AND SLEEP

Approximately 15% of the general population experiences chronic pain, Dr. Rosenfeld said, increasing to greater than 50% in older adults. In patients with chronic pain, more than 50% complain of poor or “unrefreshing” sleep.

Many pain medications can fragment sleep. For example, adverse effects of sodium oxybate, used for the treatment of narcolepsy to reduce excessive daytime sleepiness, include slower breathing, confusion, depression, edema, dizziness, vomiting, bedwetting, and sleepwalking.

The primary causes of sleep loss due to pain include back pain, headache, facial pain (eg, temporomandibular joint disorders), musculoskeletal pain, fibromyalgia, and premenstrual dysphoric disorder. Clinicians should investigate whether patients have a sleep disorder or mattress/pillow issues; their sleep environment and sleep hygiene should also be assessed. Circadian issues, such as shift work as well as medications, inadequate sleep, and exercise may also all play a role.

Dr. Rosenfeld said both deep sleep and REM appear to be helpful to “reset” pain thresholds. The mechanism of the interaction between pain and sleep is not clear but may involve 5-HT, norepinephrine, and substance P regulation. Many pain and sleep medicines can interfere with normal sleep architecture, he concluded.

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