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 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 6,6-2H2glucose.
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 μmol×kg lean body mass−1 · 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 μmol · kg lean body mass−1 · 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 μmol/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.
Partial sleep restriction during only a single night reduces insulin sensitivity of hepatic and peripheral glucose metabolism, as well as of peripheral lipolysis by 19–25%.
Abstract Aims Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study ...examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of poor subjective sleep quality with glycaemic control, self-care and daytime functioning; (3) possible risk markers for poor sleep quality. Methods In a cross-sectional study, Dutch adults with type 1 ( n = 267) or type 2 diabetes ( n = 361) completed an online survey, including the Pittsburgh Sleep Quality Index (PSQI), socio-demographic, clinical, self-care and psychological measures. Results Poor sleep quality (PSQI-score >5) was reported by 31% of adults with type 1 and 42% of adults with type 2 diabetes. Participants with good and poor sleep quality did not differ in self-reported HbA1c or the frequency of meeting lifestyle recommendations. Poor sleep quality was related to a higher self-care burden and higher levels of daytime sleepiness, fatigue, depressive and anxiety symptoms, and diabetes-specific distress. In multivariable logistic regression analyses examining risk markers, poor sleep quality was associated with depressive symptoms in adults with type 1 (OR = 1.39, 95% CI 1.25–1.54) and type 2 diabetes (OR = 1.31, 1.16–1.47), and with being female in those with type 2 diabetes (OR = 2.72, 1.42–5.20). Conclusions Poor subjective sleep quality is prevalent both in adults with type 1 and type 2 diabetes, and is related to poor daytime functioning and higher self-care burden. The temporal relation with depression and merits of therapy should be explored.
We have previously shown that acute sleep curtailment induces insulin resistance, both in healthy individuals as well as in patients with type 1 diabetes, suggesting a causal role for sleep ...disturbances in pathogenesis of insulin resistance, independent of endogenous insulin production. However, the underlying mechanisms remain unclear. This study aimed to explore the metabolic pathways affected by sleep loss using targeted metabolomics in human fasting plasma samples. Healthy individuals (n = 9) and patients with type 1 diabetes (n = 7) were studied after a single night of short sleep (4 h) versus normal sleep (8 h) in a cross-over design. Strikingly, one night of short sleep specifically increased the plasma levels of acylcarnitines, essential intermediates in mitochondrial fatty acid oxidation (FAO). Specifically, short sleep increased plasma levels of tetradecenoyl-l-carnitine (C14:1) (+32%, p = 2.67*10−4), octadecanoyl-l-carnitine (C18:1) (+22%, p = 1.92*10−4) and octadecadienyl-l-carnitine (C18:2) (+27%, p = 1.32*10−4). Since increased plasma acylcarnitine levels could be a sign of disturbed FAO, it is possible that sleep curtailment acutely induces inefficient mitochondrial function. Our observations provide a basis for further research into the role of acylcarnitines as a potential mechanistic pathway by which sleep deprivation – even short term – causes adverse metabolic effects, such as insulin resistance.
•One night of short sleep acutely increases plasma acylcarnitine levels.•Short sleep increases acylcarnitine in healthy individuals and patients with DM1.•Acylcarnitines reflect fatty acid oxidation and have pro-inflammatory properties.•Acylcarnitines may mediate the relation between short sleep and insulin resistance.
Evidence on whether habitual sleep duration and sleep quality are associated with increased insulin resistance is inconsistent. Here, we investigated the associations between different measures of ...habitual sleep with glycemic traits through cross-sectional and Mendelian randomization (MR) analyses. We assessed the associations of sleep duration and sleep quality with glycemic traits using multivariable linear regression models adjusted for potential confounders in 4672 middle-aged (45-65 years; 48% men) nondiabetic participants of the Netherlands Epidemiology of Obesity (NEO) study. Genetic variants for total, short, and long sleep duration were used as instrumental variables in MR analyses using summary-level data of glycemic traits in nondiabetic individuals (MAGIC;
= 58,074). In cross-sectional analyses, shortest sleepers (median 5.0 h of sleep per night) had 14.5% (95% confidence interval (CI): 2.0; 28.6%) higher fasting insulin level and 16.3% (95% CI: 2.7; 31.7%) higher HOMA-β. Bad sleep quality was associated with higher insulin resistance (e.g., 14.3% (95% CI: 4.7; 24.9%) higher HOMA-IR). All these associations disappeared after adjustment for BMI and the risk of sleep apnea. MR analyses did not indicate a causal association between total, short or long sleep duration and glycemic traits. Therefore, our used measures of habitual sleep duration and sleep quality are unlikely to directly associate with insulin resistance.
Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in ...wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of fasting did not show an effect on hepatic insulin sensitivity in terms of glucose production in the presence of increased hepatic TG content. In muscle, however, fasting resulted in increased insulin sensitivity, with increased muscle glucose uptake without changes in muscle TG content. In liver, fasting resulted in increased mRNA expression of genes promoting gluconeogenesis and TG synthesis but in decreased mRNA expression of genes involved in glycogenolysis and fatty acid synthesis. In muscle, increased mRNA expression of genes promoting glucose uptake, as well as lipogenesis and β-oxidation, was found.
In conclusion, 16 h of fasting does not induce hepatic insulin resistance, although it causes liver steatosis, whereas muscle insulin sensitivity increases without changes in muscle TG content. Therefore, fasting induces differential changes in tissue-specific insulin sensitivity, and liver and muscle TG contents are unlikely to be involved in these changes.
AbstractObjectiveTo assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral ...body.DesignRandomised, double blind, sham controlled clinical trial.SettingFour community hospitals in the Netherlands, 2011-15.Participants180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89).InterventionsParticipants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group.Main outcome measuresMain outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months’ follow-up.ResultsThe mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval −0.53 to 0.94) at baseline, −0.43 (−1.17 to 0.31) at one day, −0.11 (−0.85 to 0.63) at one week, 0.41 (−0.33 to 1.15) at one month, 0.21 (−0.54 to 0.96) at three months, 0.39 (−0.37 to 1.15) at six months, and 0.45 (−0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months’ follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction.ConclusionsPercutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months’ follow-up among patients with acute osteoporotic vertebral compression fractures.Trial registrationClinicalTrials.gov NCT01200277.
The aim of this study was to perform a systematic review and meta-analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls, assessed by ...hyperinsulinemic euglycemic clamp studies.
We conducted a systematic search of publications using PubMed, EMBASE, Web of Science and COCHRANE Library. Hyperinsulinemic euglycemic clamp studies comparing adult patients with type 1 diabetes mellitus to healthy controls were eligible. Primary outcome measures were pooled mean differences of insulin sensitivity of endogenous glucose production (EGP), of glucose uptake and of lipolysis. We estimated mean (standardized) differences and 95% CIs using random effects meta-analysis.
We included 38 publications in this meta-analysis. The weighed mean differences in EGP during hyperinsulinemia between patients and controls was 0.88 (95% CI: 0.47, 1.29) in the basal state and 0.52 (95% CI: 0.09, 0.95) in insulin stimulated conditions, indicating decreased hepatic insulin sensitivity in patients. Insulin sensitivity of glucose uptake was either reported as M value (M), glucose infusion rate (GIR), glucose disposal rate (GDR) or metabolic clearance rate (MCR). Weighed mean differences were similar for M -3.98 (95% CI: -4.68, -3.29) and GIR -4.61 (95% CI: -5.86, -3.53). Weighed mean difference for GDR was -2.43 (95% CI: -3.03, -1.83) and -3.29 (95% CI: -5.37, -1.22) for MCR, indicating decreased peripheral insulin sensitivity in patients. Insulin mediated inhibition of lipolysis was decreased in patients, reflected by increased non-esterified fatty acid levels.
Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic, peripheral and adipose tissues.
Prolactinomas are the most commonly encountered pituitary adenomas in the clinical setting. While most can be controlled by dopamine agonists, a subset of prolactinomas are dopamine-resistant and ...very aggressive. In such tumors, the treatment of choice is neurosurgery and radiotherapy, with or without temozolomide. Here, we report a patient with an highly aggressive, dopamine-resistant prolactinoma, who only achieved biochemical and tumor control during pasireotide long-acting release (PAS-LAR) therapy, a second-generation somatostatin receptor ligand (SRL). Interestingly, cystic degeneration, tumor cell necrosis or both was observed after PAS-LAR administration suggesting an antitumor effect. This case shows that PAS-LAR therapy holds clinical potential in selective aggressive, dopamine-resistant prolactinomas that express somatostatin (SST) receptor subtype 5 and appears to be a potential new treatment option before starting temozolomide. In addition, PAS-LAR therapy may induce cystic degeneration, tumor cell necrosis or both in prolactinomas.
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 ...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/m², 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 6,6-²H₂glucose. 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 μmol · kg lean body mass⁻¹ · min⁻¹, NS). In contrast, sleep restriction decreased the glucose disposal rate during the clamp (25.5 ± 2.6 vs. 22.0 ± 2.1 μmol · kg lean body mass⁻¹ · min⁻¹, P = 0.04), reflecting decreased peripheral insulin sensitivity. Accordingly, sleep restriction decreased the rate of glucose infusion by ~21% (P = 0.04). Sleep restriction did not alter plasma NEFA levels during the clamp (143 ± 29 vs. 133 ± 29 μmol/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.
Purpose
Osteoporotic vertebral compression fractures are treated conservatively or in selected cases with percutaneous vertebroplasty (PV). The purpose of this retrospective analysis is to determine ...predictive factors for a high visual analogue scale (VAS) pain score after conservative, sham or PV and is based on previously published randomized trials.
Methods
The VERTOS II compared conservative versus PV, and VERTOS IV compared sham versus PV treatment. The conservative group received pain medication. The sham and PV group received subcutaneous lidocaine/bupivacaine. In addition, the PV group received cementation, which was simulated in the sham group. Nineteen different predictors of high (≥ 5) versus low (< 5) VAS pain score at 12 months were investigated.
Results
20.7% of patients in the PV group demonstrated a VAS ≥ 5 at the 12-month, compared to 40.1% in the conservative or sham group, with a significant difference (
χ
2
(1) = 15.26,
p
< 0.0001, OR = 2.57, 95% CI = 1.59 to 4.15). In the subgroup analysis, we detected five predictors for the risk of high pain scores (VAS ≥ 5 after 12 months follow-up), namely: female, baseline VAS > 8, long-term baseline pain, mild/severe Genant and new fractures.
Conclusions
Statistically significant more patients had a high pain score at 12 months in the sham and conservative group when compared with the PV group. Five predictors were identified for sustained high local back pain, regardless of the received treatment. Patients with moderate fracture deformity were less likely to have high pain scores at 12 months if they received PV than if they had sham or conservative therapy.
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