Predictive factors for sustained pain after (sub)acute osteoporotic vertebral fractures:Combined results from the VERTOS II and VERTOS IV trial

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 ( 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03170-7

Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma.

peer reviewedProlactinomas 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

Insulin resistance in patients with type 1 diabetes assessed by glucose clamp studies: systematic review and meta-analysis

Objective: 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. Design and methods: 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. Results: 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. Conclusions: Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic, peripheral and adipose tissue

Subjective sleep impairment in adults with type 1 or type 2 diabetes: results from Diabetes MILES - the Netherlands

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

Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice

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

Insulin resistance in multiple tissues in patients with type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion therapy

The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls. We studied eight patients (four men and four women) with type 1 diabetes mellitus on continuous subcutaneous insulin infusion and eight healthy controls, matched for age, gender and body mass index. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with infusion of [6,6-(2) H(2)] glucose. Endogenous glucose production did not differ in the basal state between patients and controls. However, endogenous glucose production was less suppressed during clamp conditions in patients compared with controls (64% vs 79%, p = 0.01), indicating decreased hepatic insulin sensitivity. During the clamp study, glucose disposal rate was ~38% lower in patients compared with controls (24.4 ± 2.5 vs 39.7 ± 5.6 µmol/kgLBM/min, p = 0.04). Accordingly, the rate of infusion of glucose was ~51% lower in patients (17.7 ± 2.8 vs 39.7 ± 5.7 µmol/kgLBM/min, p = 0.02). Finally, non-esterified fatty acids levels were ~2.5 times higher in patients during steady state clamp conditions (150 ± 26 vs 58 ± 4 pmol/L, p = 0.01), reflecting decreased insulin sensitivity of lipolysis. Insulin resistance is a prominent feature of lean patients with type 1 diabetes mellitus, despite long term and stable treatment with continuous subcutaneous insulin infusion. Insulin resistance in type 1 diabetes involves both lipolysis, hepatic and peripheral glucose metabolis

Vertebroplasty versus active control intervention for chronic osteoporotic vertebral compression fractures:The VERTOS V randomized controlled trial

Background Evidence regarding percutaneous vertebroplasty (PV) for chronic painful osteoporotic vertebral compression fractures (OVCFs) remains limited. Purpose To compare pain relief, quality of life, and disability between PV and active control (anesthetic infiltration) interventions for chronic OVCF. Materials and Methods This prospective randomized clinical trial was conducted between May 2013 and June 2019 in participants with pain due to OVCF lasting longer than 3 months with bone marrow edema present at MRI. Study participants were randomly assigned to undergo PV ( n = 40) or active control intervention ( n = 40). The primary outcome was pain severity, assessed with the visual analog scale (VAS) (range, 0-10) during 12 months after treatment. Secondary outcomes included Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) score (range, 0-100) and Roland Morris Disability Questionnaire (RMDQ) score (range, 0-100). Outcomes were analyzed according to a longitudinal multilevel model used to test the difference between groups in change from baseline across follow-up. Results The mean age of the 80 participants (54 women) was 69 years ± 10 (SD) in the PV group and 71 years ± 10 in the active control group. VAS score was 7.6 (95% CI: 7.0, 8.2) in the PV group and 7.3 (95% CI: 6.9, 7.8) in the active control group at baseline ( P = .47) and 3.9 (95% CI: 3.1, 4.8) and 5.1 (95% CI: 4.3, 6.0), respectively, at month 12 ( P = .045). At month 12, the group difference from baseline was 1.3 (95% CI: 0.1, 2.6; P = .02) for VAS, 5.2 (95% CI: 0.9, 9.4; P = .02) for QUALEFFO, and 7.1 (95% CI: -3.3, 17.5; P = .18) for RMDQ, favoring the PV group. Conclusion In the treatment of pain caused by chronic OVCFs, PV is more effective for pain relief and quality of life improvement than anesthetic injection alone, with similar improvement for disability between the groups. </p

The Association between Habitual Sleep Duration and Sleep Quality with Glycemic Traits: Assessment by Cross-Sectional and Mendelian Randomization Analyses

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&#8211;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; n = 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-&#946;. 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

A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects

Subsequent nights with partial sleep restriction result in impaired glucose tolerance, but the effects on insulin sensitivity have not been characterized. The aim of this study was to evaluate the effect of a single night of partial sleep restriction on parameters of insulin sensitivity. 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. 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). 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 diabete