Michael Ith

Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes

BACKGROUND Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance. OBJECTIVE The aim was to assess the effects of fructose, a potent stimulator of hepatic de novo lipogenesis, on intrahepatocellular lipids (IHCLs) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders. DESIGN Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet (3.5 g x kg FFM(-1) x d(-1), +35% energy intake). Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp (0.3 and 1.0 mU x kg(-1) x min(-1)), together with 6,6-[2H2]glucose. IHCLs and intramyocellular lipids (IMCLs) were measured by 1H-magnetic resonance spectroscopy. RESULTS The OffT2D group had significantly (P < 0.05) higher IHCLs (+94%), total triacylglycerols (+35%), and lower whole-body insulin sensitivity (-27%) than did the control group. The high-fructose diet significantly increased IHCLs (control: +76%; OffT2D: +79%), IMCLs (control: +47%; OffT2D: +24%), VLDL-triacylglycerols (control: +51%; OffT2D: +110%), and fasting hepatic glucose output (control: +4%; OffT2D: +5%). Furthermore, the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group (group x diet interaction: P < 0.05). CONCLUSIONS A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity. Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group, which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes. This trial was registered at clinicaltrials.gov as NCT00523562.

Effects of a short-term overfeeding with fructose or glucose in healthy young males

Consumption of simple carbohydrates has markedly increased over the past decades, and may be involved in the increased prevalence in metabolic diseases. Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial. We therefore compared the effects of hypercaloric diets enriched with fructose (HFrD) or glucose (HGlcD) in healthy men. Eleven subjects were studied in a randomised order after 7 d of the following diets: (1) weight maintenance, control diet; (2) HFrD (3.5 g fructose/kg fat-free mass (ffm) per d, +35 % energy intake); (3) HGlcD (3.5 g glucose/kg ffm per d, +35 % energy intake). Fasting hepatic glucose output (HGO) was measured with 6,6-2H2-glucose. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured by 1H magnetic resonance spectroscopy. Both fructose and glucose increased fasting VLDL-TAG (HFrD: +59 %, P < 0.05; HGlcD: +31 %, P = 0.11) and IHCL (HFrD: +52 %, P < 0.05; HGlcD: +58 %, P = 0.06). HGO increased after both diets (HFrD: +5 %, P < 0.05; HGlcD: +5 %, P = 0.05). No change was observed in fasting glycaemia, insulin and alanine aminotransferase concentrations. IMCL increased significantly only after the HGlcD (HFrD: +24 %, NS; HGlcD: +59 %, P < 0.05). IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD, but were increased compared to values observed with a weight maintenance diet. However, glucose led to a higher increase in IMCL than fructose.

High protein intake reduces intrahepatocellular lipid deposition in humans

BACKGROUND High sugar and fat intakes are known to increase intrahepatocellular lipids (IHCLs) and to cause insulin resistance. High protein intake may facilitate weight loss and improve glucose homeostasis in insulin-resistant patients, but its effects on IHCLs remain unknown. OBJECTIVE The aim was to assess the effect of high protein intake on high-fat diet-induced IHCL accumulation and insulin sensitivity in healthy young men. DESIGN Ten volunteers were studied in a crossover design after 4 d of either a hypercaloric high-fat (HF) diet; a hypercaloric high-fat, high-protein (HFHP) diet; or a control, isocaloric (control) diet. IHCLs were measured by (1)H-magnetic resonance spectroscopy, fasting metabolism was measured by indirect calorimetry, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and plasma concentrations were measured by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry; expression of key lipogenic genes was assessed in subcutaneous adipose tissue biopsy specimens. RESULTS The HF diet increased IHCLs by 90 +/- 26% and plasma tissue-type plasminogen activator inhibitor-1 (tPAI-1) by 54 +/- 11% (P < 0.02 for both) and inhibited plasma free fatty acids by 26 +/- 11% and beta-hydroxybutyrate by 61 +/- 27% (P < 0.05 for both). The HFHP diet blunted the increase in IHCLs and normalized plasma beta-hydroxybutyrate and tPAI-1 concentrations. Insulin sensitivity was not altered, whereas the expression of sterol regulatory element-binding protein-1c and key lipogenic genes increased with the HF and HFHP diets (P < 0.02). Bile acid concentrations remained unchanged after the HF diet but increased by 50 +/- 24% after the HFHP diet (P = 0.14). CONCLUSIONS Protein intake significantly blunts the effects of an HF diet on IHCLs and tPAI-1 through effects presumably exerted at the level of the liver. Protein-induced increases in bile acid concentrations may be involved. This trial was registered at www.clinicaltrials.gov as NCT00523562.

Temperature and pressure effects during erbium laser stapedotomy

Laser‐assisted stapedotomy has become a well‐established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment.

Dynamics of laser-induced channel formation in water and influence of pulse duration on the ablation of biotissue under water with pulsed erbium-laser radiation

The ability to use fiber-delivered erbium-laser radiation for non-contact arthroscopic meniscectomy in a liquid environment was studied. The laser radiation is transmitted through a water-vapor channel created by the leading part of the laser pulse. The dynamics of the channel formation around a submerged fiber tip was investigated with time-resolved flash photography. Strong pressure transients with amplitudes up to a few hundreds of bars measured with a needle hydrophone were found to accompany the channel formation process. Additional pressure transients in the range of kbars were observed after the laser pulse associated with the collapse of the vapor channel. Transmission measurements revealed that the duration the laser-induced channel stays open, and therefore the energy transmittable through it, is substantially determined by the laser pulse duration. The optimum pulse duration was found to be in the range between 250 and 350 µS. This was confirmed by histological evaluations of the laser incisions in meniscus: Increasing the pulse duration from 300 to 800 µs leads to a decrease in the crater depth from 1600 to 300 µm. A comparison of the histological examination after laser treatment through air and through water gave information on the influence of the vapor channel on the ablation efficiency, the cutting quality and the induced thermal damage in the adjacent tissue. The study shows that the erbium laser combined with an adequate fiber delivery system represents an effective surgical instrument liable to become increasingly accepted in orthopedic surgery.

Observation and identification of metabolites emerging during postmortem decomposition of brain tissue by means of in situ 1H-magnetic resonance spectroscopy.

Postmortem decomposition of brain tissue was investigated by 1H‐magnetic resonance spectroscopy (MRS) in a sheep head model and selected human cases. Aiming at the eventual estimation of postmortem intervals in forensic medicine, this study focuses on the characterization and identification of newly observed metabolites. In situ single‐voxel 1H‐MRS at 1.5 T was complemented by multidimensional homo‐ and heteronuclear high‐resolution NMR spectroscopy of an extract of sheep brain tissue. The inclusion of spectra of model solutions in the program LC Model confirmed the assignments in situ. The first postmortem phase was characterized mainly by changes in the concentrations of metabolites usually observed in vivo and by the appearance of previously reported decay products. About 3 days postmortem, new metabolites, including free trimethylammonium, propionate, butyrate, and iso‐butyrate, started to appear in situ. Since the observed metabolites and the time course is comparable in sheep and human brain tissue, the model system seems to be appropriate. Magn Reson Med 48:915–920, 2002.

Fructose and Galactose Enhance Post-Exercise Human Liver Glycogen Synthesis

PURPOSE Both liver and muscle glycogen stores play a fundamental role in exercise and fatigue, but the effect of different CHO sources on liver glycogen synthesis in humans is unclear. The aim was to compare the effect of maltodextrin (MD) drinks containing galactose, fructose, or glucose on postexercise liver glycogen synthesis. METHODS In this double-blind, triple crossover, randomized clinical trial, 10 well-trained male cyclists performed three experimental exercise sessions separated by at least 1 wk. After performing a standard exercise protocol to exhaustion, subjects ingested one of three 15% CHO solutions, namely, FRU (MD + fructose, 2:1), GAL (MD + galactose, 2:1), or GLU (MD + glucose, 2:1), each providing 69 g CHO·h(-1) during 6.5 h of recovery. Liver glycogen changes were followed using (13)C magnetic resonance spectroscopy. RESULTS Liver glycogen concentration increased at faster rates with FRU (24 ± 2 mmol·L(-1)·h(-1), P < 0.001) and with GAL (28 ± 3 mmol·L(-1)·h(-1), P < 0.001) than with GLU (13 ± 2 mmol·L(-1)·h(-1)). Liver volumes increased (P < 0.001) with FRU (9% ± 2%) and with GAL (10% ± 2%) but not with GLU (2% ± 1%, NS). Net glycogen synthesis appeared linear and was faster with FRU (8.1 ± 0.6 g·h(-1), P < 0.001) and with GAL (8.6 ± 0.9 g·h(-1), P < 0.001) than with GLU (3.7 ± 0.5 g·h(-1)). CONCLUSIONS When ingested at a rate designed to saturate intestinal CHO transport systems, MD drinks with added fructose or galactose were twice as effective as MD + glucose in restoring liver glycogen during short-term postexercise recovery.

Inflammation and atrial remodeling after a mountain marathon

Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long‐distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic‐determined signal‐averaged P‐wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow‐up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high‐sensitivity C‐reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high‐sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise‐induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.

Infrared multiwavelength laser system for establishing a surgical delivery path through water

A multiwavelength laser system designed for precise and efficient tissue ablation under water was realized by simultaneously coupling radiation of a holmium:YAG laser, emitting at a wavelength of 2.12 μm and an erbium: YSGG laser at 2.79 μm into the same zirconium fluoride (ZrF4) fiber. The beam paths of the two lasers were collinearly combined taking advantage of the dispersion of an Infrasil prism. Fast video flash photographs and laser induced pressure transients simultaneously recorded with a PVDF pressure transducer were used to study the dynamics of bubble formation at the submerged fiber tip. The bubble size and the bubble lifetime were determined as a function of the wavelength and the delay time between the two different laser pulses. The results indicate that the combination of 2 and 3 μm radiation takes specific advantage of both wavelengths and strongly enhances the ablation efficiency of tissue under water.

Combination of fiber-guided pulsed erbium and holmium laser radiation for tissue ablation under water.

Because of the high absorption of near-infrared laser radiation in biological tissue, erbium lasers and holmium lasers emitting at 3 and 2 µm, respectively, have been proven to have optimal qualities for cutting or welding and coagulating tissue. To combine the advantages of both wavelengths, we realized a multiwavelength laser system by simultaneously guiding erbium and holmium laser radiation by means of a single zirconium fluoride (ZrF(4)) fiber. Laser-induced channel formation in water and poly(acrylamide) gel was investigated by the use of a time-resolved flash-photography setup, while pressure transients were recorded simultaneously with a needle hydrophone. The shapes and depths of vapor channels produced in water and in a submerged gel after single erbium and after combination erbium-holmium radiation delivered by means of a 400-µm ZrF(4) fiber were measured. Transmission measurements were performed to determine the amount of pulse energy available for tissue ablation. The effects of laser wavelength and the delay time between pulses of different wavelengths on the photomechanical and photothermal responses of meniscal tissue were evaluated in vitro by the use of histology. It was observed that the use of a short (200-µs, 100-mJ) holmium laser pulse as a prepulse to generate a vapor bubble through which the ablating erbium laser pulse can be transmitted (delay time, 100 µs) increases the cutting depth in meniscus from 450 to 1120 µm as compared with the depth following a single erbium pulse. The results indicate that a combination of erbium and holmium laser radiation precisely and efficiently cuts tissue under water with 20-50-µm collateral tissue damage.