Purpose:To introduce a method of independent determination of CH 2 and CH 3 components of intramyocellular lipids (IMCLs) by using long TE for spectra measurement and LCModel for spectra evaluation, to test this technique in controls and insulin-resistant subjects, and to compare results at 1.5 and 3 T. Materials and Methods:Eight healthy volunteers and 11 patients with type 2 diabetes mellitus underwent measurement using a 1.5-T MR scanner; six healthy volunteers were measured using a 3-T MR scanner. Spectra from the tibialis anterior muscle were acquired by using a point resolved spectroscopy (PRESS) sequence with the following parameters: TR/TE/ACQ ϭ 2000 msec/270 msec/256. Spectra were processed by LCModel 6.1 software with two types of adopted basis-set.Results: Spectra with good separation of both CH 2 and CH 3 components of IMCL and extramyocellular lipids (EMCLs) were obtained and the LCModel routine was successfully applied. The reproducibility comparison (N ϭ 7 at 1.5 T vs. N ϭ 5 at 3 T) showed that better results can be obtained at higher B 0 values. The comparison of the healthy and insulin-resistant subjects proved that both IMCL_CH 2 /Cr and IMCL_CH 3 /Cr ratios significantly differ. Conclusion:Long TE spectroscopy of the human muscle with IMCL quantification using the LCModel technique can detect changes in IMCL levels as well as help in the study of fatty acyl chain composition. Using a higher field strength increased the intra-individual reproducibility by approximately 150%. PROTON (1 H) MUSCLE MR spectroscopy has been frequently applied to study intramyocellular lipid (IMCL) metabolism in the past several years. Since resonances of particular lipid compartments were identified (1), several clinical studies regarding the relationship between IMCL levels and insulin resistance have been performed (2-4). In the above-mentioned studies, short echo time (10 -50 msec) spectra were mainly measured and the CH 2 signal at ϳ1.2 ppm, often referenced to creatine, for IMCL quantification was used. However, short echo time (TE) spectra contain broad resonances with uncertain lineshapes originating in metabolites with short relaxation time T2. These broad signals are located mainly around 2.1 ppm but also dominate in the CH 3 lipid region around 0.8 -1.0 ppm. This fact makes accurate quantification of short TE muscle spectra difficult. The first automatic routine suitable for the evaluation of 1 H muscle spectra was introduced by Slotboom et al (5). This routine was used by Boesch et al (6) for short TE muscle spectra evaluation. Although this routine allows the independent fitting of spectral components, in Boesch et al's (6) study, the spectral parameters of the CH 2 and CH 3 components were related by prior knowledge, probably because of massive peak overlap. LCModel (7) software version 6.1, released in June 2004, also allows the independent quantification of CH 2 and CH 3 components of lipids. However, the fully simulated basis-set adapted to the short echo time spectra fitting cannot overcome the pro...
ObjectiveOsteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove limited for patients with impaired renal function. An alternative therapy option is offered by denosumab, a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand.Patients and methodsWe evaluated 63 patients with osteoporosis (23 males and 40 females, age 56.4 ± 13.1 years) following solid organ transplantation (15 diabetic patients after simultaneous transplantation of the kidney and pancreas, 34 patients after kidney transplantation, and 14 patients with liver grafts). Osteoporosis was diagnosed according to standard DEXA examination using the Lunar Prodigy apparatus. Transplanted patients with impaired renal function were treated for osteoporosis of the lumbar spine (L-spine) and/or proximal femur with calcium and vitamin D supplementation and 60 mg of denosumab every 6 months between the years 2012 and 2017. The mean duration of the therapy was 1.65 ± 0.7 years.ResultsAfter denosumab therapy, L-spine T-scores improved across the whole group, ranging from −2.7 ± 0.09 to −1.8 ± 1.0 (p < 0.001). T-score values for the proximal femur increased from −2.5 ± 0.8 to −2.0 ± 0.7 after the therapy (p < 0.01). We observed only a mild, statistically insignificant improvement in distal forearm T-scores. The mean increase in L-spine bone mineral density (BMD) was 11.5 ± 6.2% in subjects with osteoporosis at this site and 10.4 ± 6.1% in the case of all patients. BMD of the proximal femur increased by 10.4 ± 8.3% in patients with osteoporosis and by 7.5 ± 7.3% in all patients. Denosumab therapy decreased the prevalence of osteoporosis in the L-spine from 75 to 27% (p < 0.001) and proximal femur osteoporosis from 54 to 36% (p < 0.05). Denosumab therapy reduced elevated levels of osteocalcin and beta-crosslaps (βCTX) in comparison with baseline levels (p < 0.001) across the whole group of graft recipients.ConclusionDenosumab therapy was well-tolerated and improved bone density in our group of solid organ transplant recipients. The indications are that denosumab could be a viable therapeutic option for transplanted patients with osteoporosis, especially in those with renal function impairment or bisphosphonate intolerance.
Objective: Telmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome. Design and methods: Twelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed. Results: Fasting plasma glucose was lower after telmisartan compared with placebo (P!0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor a (TNFa), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P!0.05), leptin and resistin (P!0.001) were increased, whereas TNFa was decreased (P!0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFa and leptin was increased after telmisartan treatment. Conclusions: Despite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFa during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.
Diabetic foot (DF) can develop in diabetic patients after organ transplantation (Tx) due to several factors including peripheral arterial disease (PAD), diabetic neuropathy and inappropriate DF prevention. Aim: To assess the occurrence of DF and associated risk factors in transplant patients. Methods: Fifty-seven diabetic patients were enrolled as part of this prospective study. All patients underwent organ Tx (01/2013-12/2015) and were followed up for minimum of 12 months up to a maximum of 50 months. Over the study period we evaluated DF incidence and identified a number of factors likely to influence DF development, including organ function, presence of late complications, PAD, history of DF, levels of physical activity before and after Tx, patient education and standards of DF prevention. Results: Active DF developed in 31.6% (18/57) of patients after organ Tx within 11 months on average (10.7 ± 8 months). The following factors significantly correlated with DF development: diabetes control (p = .0065), PAD (p<0.0001), transcutaneous oxygen pressure (TcPO2;p = .01), history of DF (p = .0031), deformities (p = .0021) and increased leisure-time physical activity (LTPA) before Tx (p = .037). However, based on logistic stepwise regression analysis, the only factors significantly associated with DF during the post-transplant period were: PAD, deformities and increased LTPA. Education was provided to patients periodically (2.6 ± 2.5 times) during the observation period. Although 94.7% of patients regularly inspected their feet (4.5 ± 2.9 times/week), only 26.3% of transplant patients used appropriate footwear. Conclusions: Incidence of DF was relatively high, affecting almost 1/3 of pancreas and kidney/pancreas recipients. The predominant risk factors were: presence of PAD, foot deformities and higher LTPA before Tx. Therefore, we recommend a programme involving more detailed vascular and physical examinations and more intensive education focusing on physical activity and DF prevention in at-risk patients before transplantation.
The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry (IC) is used for estimation of insulin-stimulated substrate utilization. Calculations are based on urinary urea nitrogen excretion (UE), which is influenced by correct urine collection. The aims of our study were to improve the timing of urine collection during the clamp and to test the effect of insulin on UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11). Urine samples were collected (a) over 24 h divided into 3-h periods and (b) before and during two-step clamp (1 and 10 mIU.kg-1.min-1; period 1 and period 2) combined with IC. The UE during the clamp was corrected for changes in urea pool size (UEc). There were no significant differences in 24-h UE between C and DM1 and no circadian variation in UE in either group. During the clamp, serum urea decreased significantly in both groups (p<0.01). Therefore, UEc was significantly lower as compared to UE not adjusted for changes in urea pool size both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp, UEc decreased significantly in both groups (p<0.01). UEc during the clamp was significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2 (p<0.01). The UE over 24 h and UEc during the clamp were statistically different in both C and DM1. We conclude that urine collection performed during the clamp with UE adjusted for changes in urea pool size is the most suitable technique for measuring substrate utilization during the clamp both in DM1 and C. Urine collections during the clamp cannot be replaced either by 24-h sampling (periods I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease in UEc in DM1 implicates the impaired insulin effect on proteolysis.
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