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Insomnia May Play Causal Role in Type 2 Diabetes

Frequent insomnia symptoms are associated with higher levels of haemoglobin A1c (HbA1c), implying that the sleep disorder may play a causal role in the development of type 2 diabetes (T2DM), according a new multicentre study published in Diabetes Care.

Previous studies have linked sleep disturbances with increased insulin resistance and higher plasma glucose levels. Both shorter and longer sleep durations have been shown to be associated with a higher risk of T2DM, as have insomnia, daytime napping, and chronotype (evening preference) in observational studies. However a causal relation has not been clear because of residual confounding (for example, from physical activity or diet) and reverse causality (such as, with diabetes-related nocturia or neuropathic pain interfering with sleep).

Study Details

The researchers, led by the University of Bristol and involving researchers from the universities of Manchester and Exeter in the UK and Harvard in the US therefore used data from the UK Biobank and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) to assess the effects of five self-reported sleep traits (insomnia symptoms, sleep duration, daytime sleepiness, napping, and chronotype) on HbA1c. The total sample sizes were 336,999 for Biobank, with mean age 57 years and 54% female, and 46,368 for MAGIC, mean age 53 and 52% female.

Using multivariable regression and one- and two-sample Mendelian randomization, which removes bias from the results, they found that participants who reported they often had difficulty getting to sleep or staying asleep had higher HbA1c levels than those who said they never, rarely, or only sometimes had such difficulties.

There was no clear evidence for an effect of other sleep traits on HbA1c. After excluding participants with diabetes and those with HbA1c of 48 mmol/mol or greater, the associations were somewhat attenuated but remained significant.

"Our results suggest that frequent insomnia symptoms cause higher HbA1c levels and, by implication, that insomnia has a causal role in type 2 diabetes," the team said.

The mechanisms underlying the link are unclear however. The team said that they could include mediation by depression, anxiety, bipolar disorders, or alterations in sleep physiology. They found the genetic correlations between insomnia and depression-related traits were stronger than those seen with other sleep-related traits. Another possibility is that several hormones are influenced by sleep disturbance, including evening cortisol, night-time growth hormone, and ghrelin. There are also possible influences on brain glucose utilization, alterations in the sympatho-vagal balance, and pro-inflammatory processes. Whether these hypothesised mechanisms are causal requires further exploration, they said.

Treating Insomnia Could Prevent or Reverse Diabetes

Nevertheless, the findings suggest that lifestyle or pharmacological interventions to alleviate insomnia could help to prevent or treat diabetes.

"These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycaemia and prevent diabetes," the researchers concluded.

Dr Faye Riley, research communications manager at Diabetes UK said: "We know from past research that there’s a link between sleep and a person’s risk of type 2 diabetes, but it hasn’t been clear which comes first, bad sleep or higher blood sugars, or if other factors are at play.

"This new study, funded by Diabetes UK, gives us important insights into the direction of the relationship between sleep and type 2 diabetes, suggesting that insufficient sleep can cause higher blood sugars levels and could play a direct role in the development of type 2 diabetes. Knowing this could open up new approaches to help prevent or manage the condition."

Tens of Thousands of People Could Benefit

Junxi (James) Liu, senior research associate at Bristol Medical School and corresponding author, told Medscape UK that the team used Mendelian randomization to estimate the size of possible treatment effects, and thus the potential clinical significance of the study. 

"The UK Biobank cohort is similar to the UK population in that about 28% have insomnia in both groups," he said. "We showed that an effective insomnia treatment would be expected to reduce HbA1c by around 0.24 to 0.52 SD units, whereas a 1 SD reduction in BMI (about 5 kg/m2, for example, equivalent to 14-kg weight loss in a person of average 1.7 m height) would be expected to produce around 0.12 SD reduction of HbA1c.

"The effect of reducing HbA1c via insomnia treatment appears larger than that achieved by reducing body weight (body mass index; BMI) by a large amount."

Furthermore, "analysis indicates that insomnia treatment would reverse diabetes (through lowering HbA1c levels) irrespective of any effects on body weight", Dr Liu said.

"We worked out that 27,300 people aged 40-70 in the UK population have insomnia and have HbA1c levels that are 1.08 mmol/mol above the HbA1c threshold (48 mmol/mol) used for diagnosing diabetes. If all those people received an effective insomnia treatment then their HbA1c would be predicted to fall by 1.08 mmol/mol and, therefore, they would no longer have diabetes."

The study was supported by a Diabetes UK grant.

MKR reports receiving research funding from Novo Nordisk and consultancy fees from Novo Nordisk and Roche Diabetes Care and has a modest shareholding in GlaxoSmithKline, all unrelated to this work. JB reports receiving consultancy fees from Novartis, unrelated to this work. DAL has received support from Roche Diagnostics and Medtronic Ltd for research unrelated to this work.

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