Genetic Mapping of Disposition Index and Acute Insulin Response Loci on Chromosome 11q

Palmer, Nicholette D.; Langefeld, Carl D.; Campbell, Joel K.; Williams, Adrienne H.; Saad, Mohammed F.; Norris, Jill M.; Sm, Haffner; Rotter, Jerome I.; Wagenknecht, Lynne E.; Bergman, Richard N.; Rich, Stephen S.; Bowden, Donald W.

doi:10.2337/diabetes.55.04.06.db05-0813

Cited by 35 publications

(37 citation statements)

References 35 publications

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“…4), whereas spectral EEG power in other frequency bands including theta, alpha, and sigma was unaffected [see supporting information (SI) Figs. [5][6][7]. The largest reductions were achieved, as expected, during the first two NREM cycles when delta power was reduced overall by Ϸ44-55% (P Ͻ 0.001) (Fig.…”

Section: Resultsmentioning

confidence: 50%

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Slow-wave sleep and the risk of type 2 diabetes in humans

Tasali

Leproult²,

Ehrmann³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

808

617

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There is convincing evidence that, in humans, discrete sleep stages are important for daytime brain function, but whether any particular sleep stage has functional significance for the rest of the body is not known. Deep non-rapid eye movement (NREM) sleep, also known as slow-wave sleep (SWS), is thought to be the most ''restorative'' sleep stage, but beneficial effects of SWS for physical well being have not been demonstrated. The initiation of SWS coincides with hormonal changes that affect glucose regulation, suggesting that SWS may be important for normal glucose tolerance. If this were so, selective suppression of SWS should adversely affect glucose homeostasis and increase the risk of type 2 diabetes. Here we show that, in young healthy adults, all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. SWS suppression reduced delta spectral power, the dominant EEG frequency range in SWS, and left other EEG frequency bands unchanged. Importantly, the magnitude of the decrease in insulin sensitivity was strongly correlated with the magnitude of the reduction in SWS. These findings demonstrate a clear role for SWS in the maintenance of normal glucose homeostasis. Furthermore, our data suggest that reduced sleep quality with low levels of SWS, as occurs in aging and in many obese individuals, may contribute to increase the risk of type 2 diabetes.aging ͉ sleep quality ͉ sleep disordered breathing ͉ delta waves ͉ insulin resistance H uman sleep is composed of rapid-eye-movement (REM) sleep and stages 1, 2, 3, and 4 of non-REM (NREM) sleep. The deeper stages of NREM sleep, i.e., stages 3 and 4, also known as slow-wave sleep (SWS), are thought to be the most ''restorative.'' There is indeed evidence that SWS plays a role in waking neurobehavioral function (1), particularly in memory consolidation (2, 3), but whether SWS is also important for peripheral physiological function is not known. The initiation of SWS is temporally associated with transient metabolic, hormonal, and neurophysiologic changes, all of which could potentially affect glucose homeostasis. These include decreased brain glucose utilization, stimulation of growth hormone release, inhibition of corticotropic activity, decreased sympathetic nervous activity, and increased vagal tone. We therefore hypothesized that SWS plays a role in glucose regulation and that suppression of SWS may adversely affect glucose homeostasis.To test this hypothesis, we developed an experimental model in young healthy lean individuals that was designed to selectively suppress SWS and assessed the impact of this intervention on glucose homeostasis. The EEG was continuously monitored, and SWS was suppressed by delivering acoustic stimuli of varying frequencies and intensities. The intervention was designed to substitute deep NREM sleep, i.e., stages 3 and 4, with shallow NREM slee...

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Section: Resultsmentioning

confidence: 50%

“…Inadequate beta cell compensation for a given decrease in S.I. results in a fall in DI, which is a validated marker of diabetes risk (7)(8)(9)(10). Indeed, the DI was Ϸ20% lower after SWS suppression (Fig.…”

Section: Resultsmentioning

confidence: 99%

Slow-wave sleep and the risk of type 2 diabetes in humans

Tasali

Leproult²,

Ehrmann³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

808

617

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show abstract

“…One clue has emerged from two disparate population studies-the FUSION Study of type 2 diabetes in Finland and the IRAS Family Study of several ethnicities in the U.S. (51,52). Both studies have identified a locus on chromosome 11 related to diabetes risk and linked with the DI.…”

Section: Orchestration Of Glucose Homeostasismentioning

confidence: 99%

Orchestration of Glucose Homeostasis

Bergman

2007

Diabetes

Self Cite

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“…The disposition index (DI) is the product of AIR G × SI, and is a marker of diabetes risk that is used in genetic studies. 22 In individuals with normal glucose tolerance, the product AIRg × SI remains constant because beta cell function is able to compensate for insulin resistance with increased insulin release. 23 Type 2 diabetes occurs when beta-cell function is unable to be sufficiently upregulated to compensate for insulin resistance, resulting in hyperglycemia.…”

Section: Laboratory Studies Of Glucose Metabolism and Sleep Lossmentioning

confidence: 99%

The metabolic consequences of sleep deprivation

Knutson

Spiegel

Penev

et al. 2007

Sleep Medicine Reviews

1,112

767

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The prevalence of diabetes and obesity is increasing at an alarming rate worldwide, and the causes of this pandemic are not fully understood. Chronic sleep curtailment is a behavior that has developed over the past 2-3 decades. Laboratory and epidemiological studies suggest that sleep loss may play a role in the increased prevalence of diabetes and/or obesity. Current data suggest the relationship between sleep restriction, weight gain and diabetes risk may involve at least three pathways: 1. alterations in glucose metabolism; 2. upregulation of appetite; 3. decreased energy expenditure. The present article reviews the current evidence in support of these three mechanisms that might link short sleep and increased obesity and diabetes risk.

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Genetic Mapping of Disposition Index and Acute Insulin Response Loci on Chromosome 11q

Cited by 35 publications

References 35 publications

Slow-wave sleep and the risk of type 2 diabetes in humans

Slow-wave sleep and the risk of type 2 diabetes in humans

Orchestration of Glucose Homeostasis

The metabolic consequences of sleep deprivation

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