COMISA has emerged in recent years as one of the most clinically consequential phenotypes in sleep medicine. Obstructive sleep apnea, in which the upper airway repeatedly collapses during sleep and triggers intermittent drops in blood oxygen, affects an estimated 9 to 38 percent of the general population. Insomnia, characterized by difficulty falling or staying asleep with daytime consequences, is similarly widespread. What has startled researchers is how often the two overlap: roughly 30 to 50 percent of patients with sleep apnea also report chronic insomnia symptoms, and 30 to 40 percent of chronic insomnia patients show objective evidence of sleep-disordered breathing. Crucially, the combination appears to be more than the sum of its parts. Prior studies have linked COMISA to elevated risks of cardiovascular disease and incident diabetes, exceeding the risk conferred by either disorder alone, particularly when the physiological burden is measured objectively rather than by symptoms alone.

To probe the relationship between diabetes and this dual sleep disorder, investigators turned to TURKAPNE, a prospective national registry that has enrolled adults aged 18 to 80 with suspected sleep apnea from 34 centers across Türkiye since 2017. For this cross-sectional analysis, the team included 12,715 patients who underwent full-night, in-laboratory polysomnography, the gold-standard sleep test that monitors brain waves, muscle tone, eye movements, airflow, respiratory effort, and oxygen saturation. Obstructive sleep apnea was defined as an apnea-hypopnea index of at least five events per hour, while insomnia was identified through standardized questions covering difficulty initiating sleep, sleep latency of 30 minutes or longer, trouble maintaining sleep, or use of hypnotic medications. Diabetes status was based on self-reported physician diagnosis or the use of antidiabetic medications. Participants using positive airway pressure therapy or mandibular advancement devices, and those with limited life expectancy, were excluded to keep the baseline measurements clean.

The headline numbers are striking. COMISA was present in 3,275 patients, or 25.7 percent of the cohort. Diabetes was significantly more common among those with COMISA than without it, at 22.8 percent versus 15.4 percent. Flipping the perspective, roughly one in three diabetic individuals in the cohort, 33.9 percent, met criteria for COMISA, compared with 24.1 percent of non-diabetic participants. After adjusting for age, sex, body mass index, smoking status, education level, and comorbidities, diabetes remained independently associated with COMISA, with an adjusted odds ratio of 1.17. While that figure may appear modest, in a cohort of this size and in a condition as prevalent as COMISA, it translates into a substantial population-level burden, and it held firm even after accounting for obesity, the most obvious shared risk factor.

The polysomnographic comparisons within the COMISA group tell an even more compelling story about physiological severity. Diabetic patients slept shorter overall, with a median total sleep time of 353.5 minutes versus 369.0 minutes in non-diabetics, and spent more time awake after sleep onset, 50.2 minutes versus 37.8 minutes. Their arousal index, a measure of how often the brain briefly surfaces from sleep, was 18.1 events per hour compared with 14.8. Their breathing was also markedly worse: the apnea-hypopnea index reached 30.0 events per hour versus 24.0, and the oxygen desaturation index, which counts how often blood oxygen dips each hour, hit 26.0 versus 20.0. Diabetic patients also spent more time with oxygen saturation below 90 percent and reached lower nadir saturations. Sleep architecture shifted toward lighter N1 sleep with reduced rapid eye movement sleep, a pattern associated with impaired glucose metabolism in experimental studies.

Why would diabetes and COMISA feed into each other? The proposed mechanisms run in both directions. Sleep apnea drives metabolic dysfunction through intermittent hypoxia, sympathetic nervous system activation, oxidative stress, and systemic inflammation, all of which impair insulin sensitivity and pancreatic beta-cell function. Insomnia, meanwhile, is thought to act through chronic physiological hyperarousal and dysregulation of the hypothalamic-pituitary-adrenal axis, the body’s central stress system, which elevates cortisol and disrupts glucose homeostasis. When the two disorders coexist, these pathways may amplify one another: the hyperarousal of insomnia can intensify the hypoxic and inflammatory insult delivered by apneic events, deepening insulin resistance. Conversely, diabetes itself may sabotage sleep through nocturia, peripheral neuropathy, autonomic dysfunction, and altered thermoregulation, creating a self-perpetuating cycle in which metabolic derangement and sleep disruption each worsen the other.

One intriguing detail from the data supports this bidirectional reading. Among diabetic patients with COMISA, difficulty maintaining sleep was more prevalent than difficulty initiating sleep, at 50.8 percent versus 44.0 percent for trouble falling asleep. Sleep-maintenance insomnia, waking repeatedly in the middle of the night, is precisely the symptom pattern one would expect from nocturnal hypoglycemia risk, medication effects, and the urge to urinate that accompanies poorly controlled blood sugar. The diabetic COMISA patients were also more frequently female and more often obese, and they carried heavier loads of hypertension, coronary artery disease, obstructive airway disease, hypothyroidism, and psychiatric disorders. Beyond diabetes, the regression analysis identified female sex, psychiatric disease, obstructive airway disease, smoking, lower education level, and higher body mass index as independent correlates of COMISA, sketching a portrait of a phenotype that clusters with social and medical vulnerability.

The sex difference deserves particular attention. Women with sleep apnea are known to present atypically, complaining of insomnia, fatigue, and mood disturbance rather than the classic snoring and witnessed apneas that raise suspicion in men, a pattern that contributes to systematic underdiagnosis of sleep-disordered breathing in women. Hormonal changes around menopause, including declines in progesterone and estrogen, may simultaneously increase upper airway collapsibility and insomnia prevalence. Because diabetic patients with COMISA in this cohort were more often female, clinicians evaluating women with diabetes who report poor sleep should consider that both conditions may be present and that neither should be dismissed as mere stress or menopausal discomfort.

The clinical implications are straightforward, though implementing them will require a shift in routine practice. The authors argue that individuals with diabetes should be screened systematically for both insomnia symptoms and sleep-disordered breathing, rather than waiting for one or the other to declare itself. Early identification of COMISA opens the door to integrated treatment, pairing positive airway pressure therapy for the apnea with cognitive behavioral therapy for insomnia, the first-line behavioral treatment that avoids the pitfalls of long-term hypnotic medication. Whether treating COMISA aggressively improves glycemic control and reduces cardiometabolic risk in diabetic patients remains to be tested in intervention trials, but the severity gradient documented here makes the hypothesis plausible and urgent.

The study has limitations worth keeping in view. Diabetes and comorbidities were identified by self-report and medication use rather than laboratory confirmation, insomnia was assessed with symptom questions rather than full diagnostic criteria, and details on diabetes duration, glycemic control, and specific drug classes were unavailable. Because the design is cross-sectional, causality cannot be established; the data show association, not direction. The cohort was also exclusively Turkish, which may limit generalizability. Still, with 12,715 polysomnographically characterized patients, the statistical signal is hard to dismiss. If roughly a third of people with diabetes carry a combined sleep disorder that worsens both their nights and their metabolism, then the sleep clinic and the diabetes clinic may need to stop operating as separate worlds, and the humble question about sleep quality may become one of the cheapest diagnostic tools in metabolic medicine.

Subject of Research: The association between diabetes mellitus and comorbid insomnia and obstructive sleep apnea (COMISA)

Article Title: Diabetes mellitus is associated with increased prevalence and severity of COMISA: evidence from the nationwide TURKAPNE cohort

Article References: Gürkan, C. G., Pihtili, A., Kiyan, E., Tasbakan, M. S., Basoglu, Ö. K., Arbatli, S., Aydin, S., Cilli, A., Dursunoglu, N., Baran, B., Peker, Y., Turkapne Study Group, Ursavaş, A., Annakkaya, A. N., Aksakal, A., Balcı, A., Utkusavaş, A., Ugurlu, A. Ö., Elmalı, A. D., … Zeren Uçar, Z. (2026). Diabetes mellitus is associated with increased prevalence and severity of COMISA: evidence from the nationwide TURKAPNE cohort. Journal of Clinical Sleep Medicine, 22(1), Article 103. https://doi.org/10.1007/s44470-026-00109-4

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00109-4

Keywords: diabetes mellitus, COMISA, insomnia, obstructive sleep apnea, polysomnography, sleep fragmentation, TURKAPNE cohort, insulin resistance, sleep-disordered breathing, metabolic dysfunction, intermittent hypoxia, sleep medicine

The commentary accompanies a large epidemiological analysis drawn from TURKAPNE, a nationwide Turkish sleep apnea cohort, which found that diabetes mellitus is associated with both an increased prevalence and an increased severity of COMISA. That finding matters because COMISA is not a rare curiosity. Studies of sleep clinic populations and community cohorts suggest that a substantial share of patients diagnosed with obstructive sleep apnea also report chronic insomnia symptoms, and vice versa, yet the overlap has historically been under-recognized. Patients with COMISA often fall through diagnostic cracks: their insomnia complaint may mask the apnea during a routine visit, or the apnea diagnosis may lead clinicians to dismiss the insomnia as secondary, leaving the underlying sleep fragmentation untreated.

Part of what makes COMISA biologically plausible as a driver of metabolic disease is the distinct sleep architecture it produces. Research comparing patients with COMISA against those with obstructive sleep apnea alone or insomnia alone has shown that the combined disorder is associated with a unique pattern of sleep disruption, blending the repetitive upper airway collapses and oxygen desaturations of apnea with the prolonged sleep-onset difficulties and nocturnal awakenings characteristic of insomnia. In laboratory studies, acute intermittent hypoxia, the hallmark physiological insult of sleep apnea, has been shown to impair glucose metabolism even in awake, healthy volunteers, suggesting a direct mechanistic pathway from oxygen fluctuation to insulin resistance.

The insomnia component adds its own metabolic burden. A systematic review and meta-analysis focusing on insomnia disorder characterized by objectively short sleep duration found associations with hypertension, diabetes, and elevated body mass index. In other words, the subset of insomnia patients whose bodies cannot compensate for their sleep loss with longer time in bed appears to carry measurable cardiometabolic risk. When that short, fragmented sleep is layered on top of the cyclical hypoxemia of sleep apnea, the two insults may act synergistically on the sympathetic nervous system, the hypothalamic-pituitary-adrenal axis, and inflammatory pathways, all of which are central to glucose homeostasis.

Cardiovascular data reinforce the concern. An analysis of a large sleep registry found that type 2 diabetic patients with co-morbid insomnia and sleep apnea faced elevated cardiovascular risk compared with diabetic patients who had neither or only one of the two sleep disorders. Separately, work on the so-called hypoxic burden, a quantitative measure of the oxygen desaturation load carried during sleep, has shown that this metric predicts cardiovascular disease-related mortality better than the traditional apnea-hypopnea index in large community cohorts such as the Osteoporotic Fractures in Men Study and the Sleep Heart Health Study. Sankari’s own longitudinal research on nocturnal heart rate variability, measured through R-R interval changes in a community-based cohort, has similarly pointed to autonomic dysregulation during sleep as a harbinger of adverse cardiovascular outcomes.

What the TURKAPNE findings add is epidemiological weight to the idea that the arrow may point in both directions. Diabetes is associated with more prevalent and more severe COMISA, but the mechanistic literature suggests COMISA may also worsen glycemic control, creating a potential feedback loop. Hyperglycemia can promote nocturia, neuropathic pain, and restless discomfort that fragment sleep, while fragmented, hypoxic sleep promotes insulin resistance, appetite dysregulation through altered leptin and ghrelin signaling, and weight gain, which in turn worsens both apnea severity and metabolic control. Breaking this loop, the commentary argues, requires treating the two sleep disorders together rather than sequentially.

Treatment evidence is beginning to catch up with the biology. The most striking recent development comes from trials of tirzepatide, a dual incretin agonist originally developed for diabetes and obesity, which demonstrated significant reductions in the apnea-hypopnea index in patients with obstructive sleep apnea and obesity. Meta-analytic work on weight reduction more broadly confirms that even modest weight loss produces meaningful drops in apnea severity. For patients with COMISA and type 2 diabetes, these agents occupy a uniquely attractive position, because they simultaneously target the metabolic disease, the body weight that drives airway collapse, and potentially the sleep-disordered breathing that feeds back into glycemic instability. Whether they also ameliorate the insomnia component of COMISA remains an open question that researchers are only beginning to explore.

The pharmacological picture is complicated by safety concerns on the insomnia side. Longitudinal primary care data have linked prescriptions of hypnotics and anxiolytics with increased mortality, particularly in multimorbid patients, a category that describes many older adults with type 2 diabetes and coexisting sleep disorders. This makes non-pharmacological approaches, above all cognitive behavioral therapy for insomnia, the preferred first-line option for the insomnia component, while positive airway pressure therapy remains the cornerstone of apnea treatment. The challenge, as the commentary emphasizes, is that adherence to positive airway pressure is notoriously poor among patients with comorbid insomnia, who may find the mask and airflow intolerable when they already struggle to fall asleep. Integrated treatment pathways that address both disorders from the outset, rather than treating apnea first and hoping insomnia resolves, may improve adherence and outcomes for both.

Screening represents another frontier. Obstructive sleep apnea in women, particularly around reproductive aging and menopause, is frequently missed because presenting complaints differ from the classic male phenotype of loud snoring and witnessed apneas, and insomnia symptoms can further obscure the picture. Sankari and colleagues have highlighted these screening challenges in recent work, and the same logic applies to diabetic patients of both sexes: a patient who reports difficulty falling or staying asleep should prompt clinicians to consider whether sleep-disordered breathing is hiding underneath, and a patient prescribed continuous positive airway pressure who remains fatigued should be evaluated for persistent insomnia. Simple validated screening instruments for both conditions could be deployed in endocrinology and primary care clinics at minimal cost.

The commentary’s central message is ultimately one of reframing. Coexistence is not the right word for what happens when diabetes, insomnia, and sleep apnea converge in a single patient; the evidence points toward genuine pathophysiological entanglement, with each condition amplifying the others through hypoxic stress, autonomic activation, inflammatory signaling, and behavioral pathways such as sedentary fatigue and disordered eating. Large prospective cohorts that track sleep architecture, hypoxic burden, and glycemic outcomes simultaneously will be needed to establish causality and to determine whether treating COMISA aggressively improves diabetes complications and cardiovascular survival. Until then, the practical takeaway for clinicians is clear: in a patient with type 2 diabetes who sleeps badly, neither the insomnia nor the apnea should be treated as background noise, because together they may be quietly driving the disease that brought the patient to the clinic in the first place.

Subject of Research: The bidirectional relationship between type 2 diabetes and comorbid insomnia and sleep apnea (COMISA)

Article Title: Beyond coexistence: attempting to unlock the diabetes–COMISA Link

Article References: Sankari, A. (2026). Beyond coexistence: attempting to unlock the diabetes–COMISA link. Journal of Clinical Sleep Medicine, 22(1), Article 125. https://doi.org/10.1007/s44470-026-00135-2

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00135-2

Keywords: COMISA, type 2 diabetes, obstructive sleep apnea, insomnia, sleep medicine, intermittent hypoxia, glucose metabolism, cardiovascular risk, TURKAPNE cohort, tirzepatide, cognitive behavioral therapy for insomnia, sleep architecture

The distinction matters because the two conditions demand different treatments. True insomnia is a disorder of hyperarousal, characterized by difficulty falling or staying asleep despite adequate opportunity, and it responds best to cognitive behavioral therapy for insomnia, or CBT-I, and, in some cases, carefully selected hypnotic medications. Obstructive sleep apnea, by contrast, is a mechanical and physiological problem: the upper airway collapses during sleep, oxygen levels dip, and the brain jolts the body awake just enough to reopen the airway. Its first-line treatment is positive airway pressure therapy. If a clinician mistakes apnea-driven fragmentation for insomnia and prescribes a sedative-hypnotic, the underlying breathing disorder may worsen, since hypnotics can suppress the arousal responses and upper-airway muscle tone that protect a vulnerable airway during sleep.

The letter responds directly to a recent analysis of the TURKAPNE cohort, a nationwide Turkish sleep study led by Gürkan and colleagues, which reported that diabetes mellitus is associated with increased prevalence and severity of COMISA. That finding, published in the same journal, seemed to confirm what many clinicians suspected: diabetes and the double burden of insomnia plus apnea travel together. But Xu and colleagues raise a methodological objection that cuts to the heart of how COMISA is diagnosed. Standard insomnia questionnaires, such as the Insomnia Severity Index, ask about difficulty falling asleep, frequent awakenings, and unrefreshing sleep. A patient with severe, untreated sleep apnea will answer yes to nearly all of those questions, not because their brain has forgotten how to sleep, but because their airway keeps waking them up.

This perceptual blind spot is one of the most counterintuitive findings in modern sleep science. Most people with obstructive sleep apnea do not remember the dozens or hundreds of brief arousals that fragment their night. Each arousal lasts only a few seconds, just long enough to restore airflow, and the sleeper typically falls back asleep without forming any memory of the event. What they remember is the consequence: a morning feeling of unrefreshing sleep, daytime fatigue, and the impression that they are an insomniac. When such a patient fills out an insomnia questionnaire, the answers faithfully report the symptom but misattribute the cause. In a population with high rates of obesity and apnea, such as people with type 2 diabetes, that misattribution can inflate the apparent prevalence of true insomnia comorbidity considerably.

The technical solution the letter points toward is objective sleep measurement. Polysomnography, the gold-standard sleep study, records brain waves, eye movements, muscle tone, airflow, respiratory effort, and blood oxygen saturation across a full night. It can quantify the apnea-hypopnea index, the number of breathing interruptions per hour of sleep, and it can reveal whether reported insomnia complaints correlate with objective sleep fragmentation from respiratory events. Studies of Asian patients with comorbid insomnia and sleep apnea, such as the 2025 analysis by Hoc and Lee published in Scientific Reports, have used polysomnographic characteristics to begin separating phenotypes: patients whose insomnia complaints track with respiratory-event-related arousals versus those with genuine difficulty initiating or maintaining sleep independent of breathing disturbances.

The stakes extend well beyond diagnostic bookkeeping. Large epidemiological studies have linked both sleep-disordered breathing and insomnia to cardiometabolic outcomes. The Hispanic Community Health Study/Study of Latinos, analyzed by Li and colleagues in the American Journal of Respiratory and Critical Care Medicine in 2021, found associations between sleep-disordered breathing, insomnia, and incident hypertension and diabetes. If apnea contributes to the development and worsening of diabetes through intermittent hypoxia, sympathetic activation, and impaired glucose metabolism, then misclassifying apnea as insomnia in diabetic patients does more than delay proper treatment; it obscures a potentially modifiable driver of the metabolic disease itself. Treating the apnea could, in principle, improve both sleep and glycemic control, whereas treating a phantom insomnia cannot.

The pharmacological dimension adds further urgency. A 2024 systematic review and meta-analysis by Messineo, Sands, and Labarca in the American Journal of Respiratory and Critical Care Medicine examined how hypnotic medications affect obstructive sleep apnea severity and endotypes. The evidence suggests that the effects of hypnotics on apnea are not uniform: some agents may worsen the disorder by prolonging apneas or blunting arousals, while the impact varies with the patient’s specific apnea endotype, meaning the anatomical and physiological pattern that produces their airway collapse. Prescribing a hypnotic to a diabetic patient whose insomnia symptoms are actually driven by unrecognized apnea therefore carries a real risk of aggravating the very condition that is destroying their sleep, potentially deepening both the sleep fragmentation and the metabolic consequences.

Xu and colleagues propose that studies examining COMISA in diabetes should incorporate objective respiratory monitoring before concluding that insomnia is genuinely comorbid. At minimum, they argue, the diagnostic pathway for a diabetic patient reporting chronic insomnia should include screening for sleep apnea, whether through validated questionnaires such as the STOP-BANG, home sleep apnea testing, or full polysomnography in complex cases. Only after excluding or adequately treating significant sleep-disordered breathing can a clinician confidently diagnose a true insomnia comorbidity and initiate CBT-I or hypnotic therapy on solid ground. This sequencing, they suggest, would sharpen both research definitions and everyday clinical practice, replacing a symptom-based label with a mechanism-based diagnosis.

The letter, which was received on 3 July 2026, accepted on 9 July, and published on 12 August 2026 as article 138 in volume 22 of the journal, was supported by the Gansu Provincial Natural Science Foundation under grant number 25JRRA266. The authors, who work across the departments of nephrology and diabetes, geriatrics, and rehabilitation medicine at Gansu Provincial Hospital of Traditional Chinese Medicine in Lanzhou, declare no competing interests. Their argument is deliberately modest in form but consequential in scope: it does not overturn the TURKAPNE finding, but it reframes it, asking whether the excess COMISA observed in diabetes reflects a true double sleep disorder or an apnea epidemic wearing an insomnia mask.

For the rapidly growing global population of people living with diabetes, the practical message is clear. Chronic insomnia complaints in this group should trigger a search for breathing-related sleep disruption before a diagnosis of comorbid insomnia is accepted and sedatives are prescribed. The tools to make that distinction already exist, from low-cost home sleep testing to full laboratory polysomnography, and the treatments for each condition are fundamentally different. As sleep researchers continue to refine the phenotypes of COMISA, the letter by Xu, Liu, and Liu serves as a reminder that in medicine, as in sleep itself, what appears on the surface is not always what is happening underneath. Getting the diagnosis right may be the first step toward a night of genuinely restorative sleep, and perhaps toward better metabolic health as well.

Subject of Research: Distinguishing true insomnia comorbidity from obstructive sleep apnea-related sleep disruption in patients with diabetes

Article Title: Clarifying COMISA in diabetes: distinguishing true insomnia comorbidity from OSA-related sleep disruption

Article References: Xu, S., Liu, X., & Liu, C. (2026). Clarifying COMISA in diabetes: distinguishing true insomnia comorbidity from OSA-related sleep disruption. Journal of Clinical Sleep Medicine, 22(1), Article 138. https://doi.org/10.1007/s44470-026-00154-z

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00154-z

Keywords: COMISA, insomnia, obstructive sleep apnea, diabetes, sleep medicine, polysomnography, CBT-I, hypnotics, TURKAPNE cohort, sleep fragmentation, type 2 diabetes, sleep-disordered breathing

The study followed 1,860 adults drawn at random from the resident population of Lausanne, aged between 35 and 75 at cohort entry. Unlike most previous work in this field, which relied on diagnostic codes or self-report, every participant underwent a full night of in-laboratory polysomnography, the gold standard for measuring sleep-disordered breathing. Obstructive sleep apnea was defined as an apnea-hypopnea index of at least 15 events per hour of sleep, while insomnia symptoms were captured with the Pittsburgh Sleep Quality Index, counting difficulty falling asleep within 30 minutes or waking during the night or early morning at least three times per week over the previous month. Cardiovascular outcomes — fatal and nonfatal myocardial infarction, ischemic and hemorrhagic stroke, central retinal artery occlusion, and coronary heart disease — were identified through medical records, hospital databases, and mortality registries, and then adjudicated by an expert committee of internists, cardiologists, and neurologists.

Over a median follow-up of 7.92 years, the pattern that emerged was strikingly specific. Participants with COMISA — 211 people, or 11.3 percent of the sample — had a crude hazard ratio of 3.68 for incident cardiovascular events compared with those who had neither condition. After statistical adjustment for age, sex, body mass index, diabetes, dyslipidemia, hypertension, smoking, alcohol intake, and prior cardiovascular events, the hazard ratio settled at 1.78, still clearly significant. In contrast, insomnia symptoms without sleep apnea showed no significant association with cardiovascular events, and neither did sleep apnea without insomnia symptoms. The adjusted eight-year absolute risk of a cardiovascular event was 12.9 percent in the COMISA group versus 8.1 percent in the reference group — an absolute difference of nearly five percentage points.

Perhaps the most intriguing statistical finding was a significant interaction between the two conditions. When the researchers modeled obstructive sleep apnea and insomnia as separate binary variables and included an interaction term, the hazard ratio for that interaction was 2.28, rising to 2.67 among participants free of cardiovascular disease at baseline. In plain terms, the combined hazard of having both disorders exceeded what would be expected from simply adding their individual effects — a signature of synergy rather than mere overlap. This statistical interplay is what elevates COMISA from a diagnostic curiosity to what the authors describe as a clinically relevant phenotype with its own prognostic weight.

The robustness of the result was tested from multiple angles. The team repeated the analysis using three alternative definitions of insomnia: one incorporating regular use of sleep medication, one requiring subjective wake after sleep onset of at least 30 minutes, and one requiring objectively measured wake after sleep onset of at least 30 minutes on polysomnography. COMISA remained significantly associated with cardiovascular events under every definition, with hazard ratios ranging from 1.86 to 2.14 in the full sample and up to 2.34 in participants without prior cardiovascular disease. Notably, the estimates were larger with the stricter wake-after-sleep-onset definitions, hinting that people whose apnea is punctuated by prolonged, genuine awakenings — rather than brief respiratory arousals — may represent the most vulnerable subgroup.

Sensitivity analyses reinforced the picture. Excluding participants who began continuous positive airway pressure therapy during follow-up did not eliminate the association, nor did including participants whose total sleep time fell below 240 minutes. When the outcome was restricted to cardiac events only, excluding the 35 cerebrovascular events, the association weakened and lost statistical significance — a finding the authors interpret cautiously given the small number of stroke events, but one that aligns with established links between both sleep apnea and insomnia and cerebrovascular disease.

Why should the combination of a racing mind and a collapsing airway be so much more dangerous than either alone? The authors lay out a plausible pathophysiological cascade. Insomnia is associated with physiological hyperarousal, dysregulation of the hypothalamic-pituitary-adrenal axis, elevated sympathetic tone, and metabolic disturbance. Obstructive sleep apnea contributes repetitive bouts of hypoxia, oxidative stress, dramatic swings in intrathoracic pressure, systemic inflammation, and further sympathetic activation. Together, these mechanisms could compound one another, keeping the cardiovascular system in a state of chronic nocturnal stress. A recent heart rate variability analysis of the Sleep Heart Health Study supports this view, reporting COMISA-specific autonomic dysfunction with reduced parasympathetic activity during wakefulness and heightened sympathetic activation during sleep.

Curiously, conventional markers of apnea severity told a different story. The apnea-hypopnea index, oxygen desaturation index, hypoxic burden, and respiratory arousal index were not significantly different when COMISA participants were directly compared with those who had sleep apnea alone. What did distinguish the COMISA group was sleep architecture: they spent a smaller proportion of the night in slow-wave, or N3, sleep — the deepest and most restorative stage. Previous HypnoLaus work has linked reduced delta spectral power to incident hypertension, suggesting that the microstructure of deep sleep may be a hidden determinant of cardiovascular vulnerability. The authors propose that alterations in both the macrostructure and microstructure of sleep, rather than respiratory severity per se, may drive the excess risk, and they call for advanced electroencephalographic analyses to identify the electrophysiological fingerprints of the phenotype.

The findings also carry an uncomfortable implication for sleep medicine. Large randomized trials have repeatedly failed to show that continuous positive airway pressure therapy prevents cardiovascular events in unselected patients with sleep apnea, and this study offers a possible explanation: comorbid insomnia may act as an effect modifier, diluting any cardiovascular benefit of treating the airway alone. The authors argue that systematic screening for insomnia symptoms in patients diagnosed with sleep apnea — and vice versa — could sharpen risk stratification. Encouragingly, cognitive behavioral therapy for insomnia has been shown to improve adherence to positive airway pressure therapy, and treating the apnea may in turn ease insomnia symptoms in some patients, opening the door to integrated treatment strategies whose cardiovascular impact now needs to be tested directly.

The study is not without limitations. Insomnia was assessed with a questionnaire that does not fully align with formal diagnostic criteria for chronic insomnia disorder, and symptoms were measured only at baseline, so the results reflect the prognostic value of COMISA as it existed at the start of follow-up rather than persistent insomnia over time. Residual confounding, as always in observational research, cannot be excluded. Yet the strengths are considerable: a randomly sampled general population, objective full-night polysomnography, expert-adjudicated outcomes, more than seven years of follow-up, and consistent results across multiple definitions and subgroups. Taken together with earlier, more heterogeneous studies, the work makes a compelling case that COMISA deserves recognition as a distinct, high-risk entity — one that clinicians can no longer afford to treat as two separate problems, and one that may hold the key to finally reducing the cardiovascular toll of disordered sleep.

Subject of Research: The association between comorbid insomnia and obstructive sleep apnea (COMISA) and incident cardiovascular events in a population-based cohort

Article Title: Comorbid insomnia and sleep apnea (COMISA) and incident cardiovascular risk: a prospective analysis from the HypnoLaus cohort

Article References: Solelhac, G., Imler, T., Marchi, N.-A., Baillieul, S., Van Den Broecke, S., Caetano, G., Heiniger, G., Waeber, A., Ericson, I., Bayon, V., Lombardi, A.-S., Haba-Rubio, J., Vollenweider, P., Marques-Vidal, P., & Heinzer, R. (2026). Comorbid insomnia and sleep apnea (COMISA) and incident cardiovascular risk: a prospective analysis from the HypnoLaus cohort. eClinicalMedicine, 100, Article 104227. https://doi.org/10.1016/j.eclinm.2026.104227

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104227

Keywords: COMISA, insomnia, obstructive sleep apnea, cardiovascular risk, polysomnography, HypnoLaus, sleep medicine, hypertension, stroke, myocardial infarction, CPAP, cognitive behavioral therapy

The dispute began with a paper from the TURKAPNE Study Group, led by Canan Gündüz Gürkan of Süreyyapaşa Chest Diseases Research and Training Hospital in Istanbul and Yüksel Peker, a pulmonary medicine specialist whose affiliations span Koç University in Istanbul, the University of Gothenburg, Lund University, and the University of Pittsburgh. Drawing on a nationwide Turkish cohort of adults evaluated for sleep-disordered breathing, the group reported that diabetes mellitus was associated with both an increased prevalence and an increased severity of a condition known by the acronym COMISA: co-morbid insomnia and sleep apnea. The finding landed with force because COMISA sits at the intersection of two of the most common chronic sleep disorders, and because patients who carry both conditions simultaneously are known to fare worse than those with either alone.

COMISA is not a niche concern. Epidemiological surveys across multiple countries suggest that a substantial fraction of patients presenting at sleep clinics with obstructive sleep apnea also report chronic insomnia symptoms, and conversely that many insomnia patients show objective evidence of upper airway obstruction during sleep. The clinical consequences of this overlap are well documented in the review literature: people with COMISA tend to report greater daytime sleepiness, more fatigue, worse quality of life, higher rates of depression and anxiety, and greater healthcare utilization than patients with a single disorder. Treatment is also trickier, because continuous positive airway pressure, the standard therapy for sleep apnea, can be poorly tolerated by patients whose insomnia makes it difficult to sleep while wearing a mask, and hypnotic medications used for insomnia can suppress arousal responses that protect apnea patients from prolonged airway collapse.

Into this landscape stepped Xu, Liu, and Liu, whose letter to the journal bore a title that framed the entire controversy: Clarifying COMISA in diabetes: distinguishing true insomnia comorbidity from OSA-related sleep disruption. Their argument, as the title suggests, was methodological and conceptual. They contended that the TURKAPNE analysis may have conflated two fundamentally different phenomena. On one side stands genuine insomnia disorder, a condition defined by persistent difficulty initiating or maintaining sleep despite adequate opportunity, accompanied by daytime impairment, and rooted in the hyperarousal mechanisms that modern insomnia research has mapped with increasing precision. On the other side stands something quite different: the fragmented, unrefreshing sleep that results when the upper airway repeatedly collapses during the night, triggering micro-awakenings that patients may perceive as insomnia.

This distinction matters because the two conditions demand different treatments and carry different prognoses. A patient whose sleep complaints are driven entirely by untreated apnea may find their insomnia-like symptoms dissolve once positive airway pressure therapy stabilizes their breathing. A patient with true co-morbid insomnia, by contrast, will typically continue to struggle with sleep even after their apnea is controlled, and will need cognitive behavioral therapy for insomnia or pharmacological treatment in addition to their breathing therapy. If researchers label apnea-related sleep fragmentation as insomnia, they inflate the apparent prevalence of COMISA, overestimate its burden in populations such as people with diabetes, and risk sending clinicians down the wrong therapeutic path.

The TURKAPNE investigators responded in a reply published on 13 August 2026, and their response defends the clinical reality of the association they reported. Peker and Gürkan, writing on behalf of the TURKAPNE Study Group, stand by the central claim of their original paper: that in their nationwide cohort, diabetes mellitus was associated with increased prevalence and severity of COMISA. The reply, published as a letter in volume 22 of the Journal of Clinical Sleep Medicine, represents the group’s formal answer to the critique, and it underscores how seriously the original authors take the challenge to their interpretation. The exchange is compact, but the stakes it illuminates are anything but.

Why would diabetes be expected to sit at the center of this storm in the first place? The physiological connections between type 2 diabetes and disordered sleep run in both directions. Obesity, the dominant risk factor for obstructive sleep apnea, is also the dominant driver of insulin resistance, so the two conditions travel together at the population level. But the links go deeper than shared adiposity. Intermittent hypoxia and sleep fragmentation from apnea activate sympathetic nervous system outflow and stress hormone release, worsen glucose tolerance, and promote insulin resistance, creating a plausible causal pathway from breathing disorder to metabolic disease. Conversely, diabetic autonomic neuropathy can destabilize the neural control of upper airway muscles and breathing rhythm, and diabetes-related nocturia and peripheral neuropathy can fragment sleep independently of any breathing problem. Insomnia, for its part, has been repeatedly linked to impaired glucose metabolism in large cohort studies, with chronic short sleep and poor sleep quality both associated with elevated diabetes risk.

This dense web of interconnection is precisely what makes the conceptual question raised by the letter writers so difficult and so important. In a patient with diabetes, poor sleep could reflect apnea-driven fragmentation, true insomnia with its hyperarousal physiology, painful neuropathy, nocturia from poor glycemic control, depression, medications, or some tangled combination of all of these. Disentangling those threads requires careful phenotyping: polysomnography to quantify apnea severity objectively, validated insomnia instruments that probe the subjective experience of sleep and its daytime consequences, and enough clinical detail to separate apnea-related awakenings from the difficulty falling asleep and staying asleep that characterizes insomnia disorder. Large registries and cohorts such as TURKAPNE, which has previously published cross-sectional analyses of more than twelve thousand adults with moderate-to-severe obstructive sleep apnea, offer the statistical power to detect associations, but their ability to resolve fine diagnostic distinctions depends entirely on the instruments used and the definitions applied.

The broader field has been converging on a more nuanced view of COMISA in recent years. Reviews of the co-morbid insomnia and sleep apnea literature, including influential work by Sweetman and colleagues, have emphasized that the overlap is real, that it is more common than chance would predict, and that it carries additive clinical burden. At the same time, researchers have acknowledged that the boundary between the two disorders is porous, that subjective insomnia symptoms can be produced or amplified by objective sleep disruption, and that the field still lacks a universally accepted algorithm for deciding when the two conditions are genuinely co-present. Some investigators have proposed sequential treatment trials, using the response to apnea therapy as a diagnostic probe: if insomnia symptoms persist after the breathing disorder is adequately treated, that persistence itself becomes evidence for true co-morbidity. Others advocate for parallel treatment pathways that address both conditions from the outset, arguing that waiting for diagnostic clarity delays relief for patients who are suffering.

What the exchange in the Journal of Clinical Sleep Medicine ultimately demonstrates is that a single word, comorbidity, can carry enormous weight. If the TURKAPNE finding survives the methodological scrutiny, it suggests that diabetes should be treated as a red flag for combined sleep pathology, prompting clinicians who evaluate diabetic patients with sleep complaints to look for both disorders rather than stopping at the first diagnosis. If the critics are right that part of the observed association reflects apnea-related sleep disruption masquerading as insomnia, then the clinical message shifts: the priority is aggressive detection and treatment of sleep apnea in diabetic patients, with insomnia reassessed only after breathing is stabilized. Either way, the practical takeaway for patients is the same. People with diabetes who struggle with sleep should not accept fragmented nights as an inevitable feature of their disease, because the causes are identifiable, the diagnostic tools exist, and effective treatments are available for both conditions. The scientific argument over definitions will continue in the letters pages, but its resolution will shape real decisions in sleep clinics, and for the growing global population living with diabetes, those decisions could determine whether restorative sleep remains out of reach or finally comes within grasp.

Subject of Research: Co-morbid insomnia and sleep apnea (COMISA) in patients with diabetes mellitus

Article Title: Reply to “Clarifying COMISA in diabetes: distinguishing true insomnia comorbidity from OSA-related sleep disruption”

Article References: Peker, Y., Gürkan, C. G., & on behalf of the TURKAPNE Study Group (2026). Reply to “Clarifying COMISA in diabetes: distinguishing true insomnia comorbidity from OSA-related sleep disruption”. Journal of Clinical Sleep Medicine, 22(1), Article 141. https://doi.org/10.1007/s44470-026-00158-9

Image Credits: AI Generated

DOI: 10.1007/s44470-026-00158-9

Keywords: COMISA, insomnia, obstructive sleep apnea, diabetes mellitus, type 2 diabetes, sleep medicine, TURKAPNE cohort, sleep fragmentation, CPAP therapy, cognitive behavioral therapy, sleep disorders, diagnostics