The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes

Figures & data

Figure 1 The mammalian core components of the clock system.

Notes: The circadian clock consists of transcription/translation feedback loops. The positive regulatory components are transcription factors CLOCK and BMAL1, which heterodimerize and bind to the E Box of clock target genes and activate downstream genes. These target genes are the period (Per 1, 2, and 3), cryptochrome (CRY1 and 2), REV-ERB, RORs, and other clock controlled genes.
Abbreviations: AMPK, adenosine monophosphate-activated protein kinase; NAD+, nicotinamide adenine dinucleotide; NAMPT, nicotinamide phosphoribosyltransferase; CKI, casein kinase I; PPARα, peroxisome proliferator-activated receptor alpha; CLOCK, circadian locomotor output cycles kaput; BMAL1, brain and muscle Arnt-like protein; PGC1-α, peroxisome proliferator-activated receptor gamma co-activator 1-alpha.

Figure 2 Behavioral factors that may affect the development of type 2 diabetes are influenced by shift work, eating behavior (breakfast skipping, night eating), and sleep loss (sleep restriction, sleep fragmentation).

Notes: These components affect circadian asynchrony. Accumulated evidence suggests that disruption of circadian synchronization between periods of rest and activity with feeding or fasting, and energy storage or energy utilization may be tightly linked to not only obesity, but also glucose metabolism, vascular reactivity, and lipid homeostasis. Copyright © 2008, Elsevier. Reprinted from Green CB, Takahashi JS, Bass J. The meter of metabolism. Cell. 2008;134(5):728–742, with permission from Elsevier.⁷⁵
Abbreviations: GH, growth hormone; CLOCK, circadian locomotor output cycles kaput; BMAL1, brain and muscle Arnt-like protein.

Table 1 Summary of the behavioral aspects of circadian rhythm in relation to development of type 2 diabetes mellitus

Authors	Year of publication	Methods	Main results	Ref no
Shift work
Mikuni et al	1983	Japanese 9,000 males age-and weight-adjusted prevalence	Prevalence of diabetes 2.1% in all three shifts 0.9% in only day shifts	51
Kawakami et al	1999	Japanese 2,194 males 8-year prospective cohort study occurrence of NIDDM Diabetes criteria WHO	Age adjusted incidence per 1,000 person years Rotating shift 2.04 Day only 1.90	52
Morikawa et al	2005	Japanese 2,860 males 8-year prospective cohort study occurrence of diabetes HbAlc 5.7%<	Diabetes incidence rate of 4.41/1,000 person years relative risk of diabetes mellitus two-shift 1.73. Three-shift 1.33	53
Kroenke et al	2007	62,574 US women 94% White 6-year prospective cohort study Nurses’ Health Study II surveys ascertainment of type 2 diabetes	Duration of rotating shift Age adjusted relative risk 5–< 10 years 1.59, 10 years 1.64 Multivariate-adjusted model 2 adjusted for BMI	54
Pan et al	2011	69,269 women aged 42-67 in Nurses’ Health Study I (NHS I) 107,915 women aged 25–42 in NHS II 18–20 years cohort study	5–< 10 years 1.14, 10 years 0.98 Pooled hazard ratios participants with >20 years of shift work 1.58 (P<0.001) adjusted for updated BMI participants with >20 years 1.24 (Ρ<0.001)	55
Erikson et al	2013	3,205 women and 2,227 men aged 35–56 years 8–10 years population- based cohort study baseline normal OGTT	Odds ratio for shift work in women Age adjusted 2.3, multi-factor adjusted 1.9 Odds ratio for shift work in men Age adjusted 0.9, multi factor adjusted 0.8	56
Eating behavior
Keski-Rahkonen	2003	Five birth cohorts of adolescent twins and their parents 16-year-old girls and boys (n=5,448) and their parents (n=4,660)	Adjusted odds ratios for BMI 25 or more Breakfast a few times a week: 1.41 Breakfast once a week or less often: 2.00	58
Cho et al	2003	NHANES III	Breakfast skippers and meat and egg eaters had higher BMI	59
Niemeir et al	2006	9,919 adolescents in Waves II (age 11–21) and III (age 18–27) of the National Longitudinal Study of Adolescent Health	Fewer days of breakfast consumption at Wave II and decreases in breakfast consumption between Waves II and III predicted increased BMI at Wave III	60
Odegaard et al	2013	3,598 participants from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study	Eating breakfast daily gained 1.9 kg less weight over 18 years (Ρ=0.001) Hazard ratio for type 2 diabetes was 0.81 (0.63-1.05)	61
Morse et al	2012	714 tertiary care patients with type 1 and 2 diabetes	Patients with night eating behaviors were more likely to be obese (odds ratio 2.6) and to have two or more diabetes complications (odds ratio 2.6)	63
Sleep loss
Vgontzas et al	2004	25 young, healthy, normal sleepers (12 men and 13 women), 1 week of sleep restriction (for only 2 hours)	24-hour secretion of IL-6 was increased by 0.8±0.3 pg/mL (P<0.05) in both sexes, TNF was increased only in men	70
Tasali et al	2008	Nine healthy volunteers (age 20–31 years; five men and four women). Experimental suppression of slow-wave sleep	Marked decreases in insulin sensitivity without adequate compensatory increase in insulin release with increased diabetes risk	7i
Scheer et al	2009	Ten adults (5 female) underwent a 10-day laboratory protocol 12 hours out of phase from their habitual times	Decreased leptin (17%, P<0.001) Increased glucose (6%, P<0.001) Increased insulin (22%, P=0.006)	72

Note: The results are summarized in this table.

Abbreviations: NIDDM, non-insulin dependent diabetes mellitus; WHO, World Health Organization; OGTT, oral glucose tolerance test; NHANES, National Health and Nutrition Examination Survey; BMI, body mass index; IL-6, interleukin 6; TNF, tumor necrosis factor; HbA_1c, glycated hemoglobin.

Green CB, Takahashi JS, Bass J. The meter of metabolism. Cell. 2008;134(5):728–742.

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