The studies performed in this thesis show that type 1 diabetes mellitus is characterized not only by insulin deficiency, but also by insulin resistance. Both hepatic and peripheral insulin... Show moreThe studies performed in this thesis show that type 1 diabetes mellitus is characterized not only by insulin deficiency, but also by insulin resistance. Both hepatic and peripheral insulin sensitivity were decreased in patients with type 1 diabetes mellitus, as well as inhibition of lipolysis. However, insulin resistance is not a fixed pathophysiological condition in type 1 diabetes. We demonstrated that a single night of partial sleep deprivation decreased insulin sensitivity by 14-20% in patients with type 1 diabetes and by 20-25% in healthy controls. These effects of partial sleep restriction could not be explained by a reduction of total slow wave sleep in patients with type 1 diabetes. Sleep duration is a determinant of insulin sensitivity, also in patients with diabetes. In addition, various aspects of diabetes could be linked to increased prevalence of sleep disturbances. Impaired sleep and type 1 diabetes might potentiate each other in some patients, thereby creating a negative vicious circle. Optimizing sleep duration and sleep quality could therefore be considered as a potential therapeutic target to improve metabolic control in patients with type 1 diabetes. Show less
Donga, E.; Dijk, M. van; Hoogma, R.P.L.M.; Corssmit, E.P.M.; Romijn, J.A. 2013
OBJECTIVE: Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in... Show moreOBJECTIVE: Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied seven patients (three men, four women) with type 1 diabetes: mean age 44 +/- 7 years, BMI 23.5 +/- 0.9 kg/m(2), and A1C 7.6 +/- 0.3%. They were studied once after a night of normal sleep duration and once after a night of only 4 h of sleep. Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with an infusion of [6,6-(2)H(2)]glucose. RESULTS Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (469 +/- 8.5 vs. 222 +/- 7.1 min, P = 0.02). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids (NEFAs), or endogenous glucose production. Endogenous glucose production during the hyperinsulinemic clamp was not altered during the night of sleep restriction compared with the night of unrestricted sleep (6.2 +/- 0.8 vs. 6.9 +/- 0.6 micromol x kg lean body mass(-1) x min(-1), NS). In contrast, sleep restriction decreased the glucose disposal rate during the clamp (25.5 +/- 2.6 vs. 22.0 +/- 2.1 micromol x kg lean body mass(-1) x min(-1), P = 0.04), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 21% (P = 0.04). Sleep restriction did not alter plasma NEFA levels during the clamp (143 +/- 29 vs. 133 +/- 29 micromol/l, NS). CONCLUSIONS: Partial sleep deprivation during a single night induces peripheral insulin resistance in these seven patients with type 1 diabetes. Therefore, sleep duration is a determinant of insulin sensitivity in patients with type 1 diabetes. Show less
Donga, E.; Dijk, M. van; Dijk, J.G. van; Biermasz, N.R.; Lammers, G.J.; Kralingen, K. van; ... ; Romijn, J.A. 2010
BACKGROUND: Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. OBJECTIVE: The aim of this... Show moreBACKGROUND: Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. OBJECTIVE: The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity. RESEARCH DESIGN AND METHODS: Nine healthy subjects (five men, four women) were studied once after a night of normal sleep duration (sleep allowed from 2300 to 0730 h), and once after a night of 4 h of sleep (sleep allowed from 0100 to 0500 h). Sleep characteristics were assessed by polysomnography. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies (from 1130 to 1430 h) with infusion of [6,6-(2)H(2)]glucose. RESULTS: Sleep duration was shorter in the night with sleep restriction than in the unrestricted night (226 +/- 11 vs. 454 +/- 9 min; P< 0.0001). Sleep restriction did not affect basal levels of glucose, nonesterified fatty acids, insulin, or endogenous glucose production. Sleep restriction resulted in increased endogenous glucose production during the hyperinsulinemic clamp study compared to the unrestricted night (4.4 +/- 0.3 vs. 3.6 +/- 0.2 micromol x kg lean body mass(-1) x min(-1); P = 0.017), indicating hepatic insulin resistance. In addition, sleep restriction decreased the glucose disposal rate during the clamp (32.5 +/- 3.6 vs. 40.7 +/- 5.1 micromol x kg lean body mass(-1) x min(-1); P = 0009), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by approximately 25% (P = 0.001). Sleep restriction increased plasma nonesterified fatty acid levels during the clamp study (68 +/- 5 vs. 57 +/- 4 micromol/liter; P = 0.005). CONCLUSIONS: Partial sleep deprivation during only a single night induces insulin resistance in multiple metabolic pathways in healthy subjects. This physiological observation may be of relevance for variations in glucoregulation in patients with type 1 and type 2 diabetes. Show less
