One-year Results of Health-related and Vision-related Quality of Life After Clear Lens Extraction and Multifocal Intraocular Lens Implantation.

PURPOSE: Multifocal intraocular lenses (MIOLs) are effective in treating presbyopia before cataracts develop. This study measured health-related quality of life (HRQoL) and vision-related quality of life (VRQoL) after clear lens extraction (CLE) and MIOL implantation. DESIGN: Before-and-after study METHODS: Patients were treated in Medilaser Coronaria, CorGroup, Oulu, Finland. HRQoL was measured by a generic 15-dimension (15D) instrument. VRQoL was measured with Visual Function Index-14 (VF-14) questionnaire. RESULTS: CLE and MIOL implantation was performed in 137 patients. The patient age was 57 ± 6.2 years (mean ± standard deviation), and 58% were women. The near add was 2.1±0.3 diopters (D). The overall HRQoL 15D score increased from 0.938±0.058 to 0.955±0.057 at 6 months (P < .0001 vs baseline) and to 0.948±0.060 at 1 year (P = .02 vs baseline). The VRQoL VF14 score increased from 85.32±15.57 to 96.57±5.07 at 6 months (P < .0001 vs baseline) and to 96.61±6.48 at 1 year (P < .0001 vs baseline). The increase of HRQoL was correlated with the increase of VRQoL (P < .04). CONCLUSIONS: CLE and MIOL implantation improved HRQoL and VRQoL compared to spectacles in this 1-year follow-up study. Improvement of HRQoL was correlated with VRQoL.

Cataract complications study: an analysis of adverse effects among 14,520 eyes in relation to surgical experience.

BACKGROUND: To evaluate the learning-curve in performing cataract surgery with respect to developments in technology and different teaching strategies by comparing the incidence of capsular bag-related complications to operator experience. METHODS: A review of the registry of 14,520 cataract surgeries carried out at the Ophthalmology Unit of Kymenlaakso Central Hospital, Kotka, Finland, from August 8, 2009 to July 31, 2017. RESULTS: We identified 144 cases with posterior capsule rupture and/or loss of capsular bag support (incidence 0.99% of all surgeries). The mean age of patients was 76.9±9.1 years and gender distribution ratio 29:71 male:female. Pseudoexfoliation syndrome (PXF; incidence 21%) and small pupil (incidence 14%) were over-represented in complication eyes, especially at the beginning of the study. Capsular bag-related complication rates were reported in 0.36% of surgeries for senior and 7.03% for resident surgeons at the beginning of the study, compared to 0.32% and 1.32%, respectively, at the end of the study. Best-corrected visual acuity at the final post-operative visit was 0.61±0.16 decimals at the beginning of the study, and 0.81±0.19 decimals at the end of the study. The mean number of post-operative visits was 4.3±2.7 and did not show trend over the study period. CONCLUSIONS: Real-world evidence suggests PXF and small pupil as significant risk factors in cataract surgery. A gradual decline in the rate complications was noted with increasing surgical experience, also among residents over the follow-up period.

Preoperative anti-inflammatory treatment of diabetic patients does not improve recovery from cataract surgery when postoperatively treated with a combination of prednisolone acetate and nepafenac.

PURPOSE: To examine preoperative anti-inflammatory treatment on recovery from cataract surgery in eyes of diabetic patients. METHODS: A Prospective randomized clinical trial. One hundred and three eyes of 103 patients with diabetes undergoing routine cataract surgery were randomized (1:1) not to receive any preoperative anti-inflammatory medication or to receive preoperative topical anti-inflammatory medication with a combination of prednisolone acetate (10 mg/ml) and nepafenac (1 mg/ml). All eyes received postoperative anti-inflammatory combination therapy for 3 weeks. Recovery from surgery was recorded by a structured home questionnaire. Clinical outcome parameters were recorded at 28 days and 3 months. RESULTS: Patient age and gender distribution, and all baseline ophthalmic and systemic parameters were comparable between the study groups. After surgery, conjunctival injection lasted 2.4 ± 1.7 days (mean ± SD) and irritation of the eye 3.3 ± 3.9 days in eyes without preoperative treatment, when compared to 1.6 ± 1.6 days (p = 0.067) and 2.4 ± 4.0 days (p = 0.431), respectively, in eyes with preoperative treatment. At 28 days, central subfield macular thickness (CSMT) increased 2.2 ± 20.2 µm in eyes without preoperative treatment, when compared 0.1 ± 25.2 µm (p = 0.670) in eyes with preoperative treatment. At 3 months, the respective CSMT change from baseline was -1.5 ± 26.9 µm and -3.4 ± 26.2 µm (p = 0.762). None of the eyes were reported with pseudophakic cystoid macular oedema (PCME) in either group. CONCLUSION: Lack of preoperative anti-inflammatory treatment does not impair recovery from surgery or predispose diabetic patients to increased risk of PCME in eyes postoperatively treated with combination therapy of prednisolone acetate and nepafenac.

Effects of bariatric surgery on retinal microvascular architecture in obese patients.

STUDY AIM: Retinal microvasculature changes reflect systemic small vessel damage from obesity. The impact of bariatric surgery induced weight loss on the microvasculature is relatively unknown. We hypothesized that weight loss following bariatric surgery would be associated with improved structural changes in the retinal microvasculature, reflecting an overall improvement in microvascular health. METHODS: The study included 22 obese subjects scheduled for bariatric surgery (laparoscopic Roux-en-Y gastric bypass or a sleeve gastrectomy) and 15 lean, age-matched controls. Ophthalmic examination, including fundus photography, was performed at baseline and 6-months. Retinal microvasculature caliber was analysed quantitatively using a semi-automated computer program and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE). RESULTS: Mean weight loss at 6 months was 26.1 kg ± 8 kg in the bariatric surgery group. Retinal artery caliber increased (136.0 ± 1.4 to 141.4 ± 1.4 µm, p = 0.013) and venular caliber decreased (202.9 ± 1.9 to 197.3 ± 1.9 µm, p = 0.046) in the bariatric surgery group by 6 months, with no change in arteriolar (136.6 ± 1.1 to 134.5 ± 1.2, p = 0.222) or venular (195.1 ± 2.1 to 193.3 ± 2.2, p = 0.550) caliber in the control group. The arteriolar to venular ratio increased in the bariatric surgery group, with no change in the control group at 6 months. CONCLUSIONS: The findings suggest obesity-related microvascular changes are reversible after bariatric surgery-induced weight loss. The capacity for the retinal microvasculature to improve following bariatric surgery suggests plasticity of the human microvasculature early in the disease course.

The effect of bariatric surgery on intraocular pressure.

PURPOSE: Study purpose was to investigate the effects of bariatric surgery on intraocular pressure (IOP) and other ophthalmic parameters in a prospective observational follow-up study. METHODS: Ophthalmic examination was performed on 22 obese women before and 6 months after bariatric surgery. A control group of 15 non-obese age-matched women were studied twice 6 months apart. IOP was measured with the Goldmann applanation tonometer (GAT) and the Pascal dynamic contour tonometer (PDCT). None of the subjects had glaucoma. RESULTS: Average weight loss 6 months after bariatric surgery was 25 ±8 kg, (p < 0.05). Visual acuity (VA), pachymetry and systolic as well as diastolic blood pressures did not differ between the obese and control groups and no change between the visits was detected. At baseline, IOP was significantly higher in the obese group than in the controls (16.6 ± 3.0 mmHg GAT and 18.1 ± 2.2 mmHg PDCT compared with 14.3 ± 1.5 mmHg GAT and 16.5 ± 1.9 mmHg PDCT respectively). After bariatric surgery, IOP was significantly lower (15.2 ± 2.7 mmHg GAT and 16.5 ± 2.0 mmHg PDCT, p < 0.05) and no significant difference was detected between the operated and control groups. In the whole data at baseline, IOP correlated with weight, body mass index, waist circumference, body fat per cent and systolic blood pressure values. CONCLUSION: Intraocular pressure (IOP) is significantly higher in obese women than in non-obese age-matched controls. Obese subjects had a decrease in IOP after bariatric surgery with no change in IOP in the control group. This change in obese group may be related to weight loss. Different measures of obesity correlated with IOP at baseline.

Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome.

AIMS/HYPOTHESIS: Obesity causes an imbalance in fat mass distribution between visceral and subcutaneous adipose tissue (AT) depots. We tested the hypothesis that this relates to increased NEFA uptake between these depots in obese compared with healthy participants. Second, we hypothesised that a diet very low in energy (very low calorie diet [VLCD]) decreases fat mass in obese participants and that this is associated with the decline in NEFA uptake. METHODS: NEFA uptake in AT depots was measured with [(18)F]-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA) and positron emission tomography (PET) in 18 obese participants with the metabolic syndrome before and after a 6 week VLCD. Whole body fat oxidation was measured using indirect calorimetry and [U-(13)C]palmitate. Sixteen non-obese participants were controls. RESULTS: Obese participants had >100% higher (p < 0.0001) NEFA uptake in the visceral and subcutaneous abdominal AT depots than controls. VLCD decreased AT mass in all regions (12% to 21%), but NEFA uptake was decreased significantly (18%; p < 0.006) only in the femoral AT. Whole body carbohydrate oxidation decreased, while fat oxidation increased. CONCLUSIONS/INTERPRETATION: The data demonstrate that weight loss caused by VLCD does not affect abdominal fasting NEFA uptake rates. We found that visceral fat takes up more NEFAs than subcutaneous AT depots, even after weight loss.

Increased brain fatty acid uptake in metabolic syndrome.

OBJECTIVE: To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS: We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [(11)C]-palmitate and [(18)F]fluoro-6-thia-heptadecanoic acid ([(18)F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS: At baseline, brain global fatty acid uptake derived from [(18)F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [(11)C]-palmitate was 86% higher. Brain fatty acid uptake measured with [(18)F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS: To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction.

Higher free fatty acid uptake in visceral than in abdominal subcutaneous fat tissue in men.

Visceral adipose tissue has been shown to have high lipolytic activity. The aim of this study was to examine whether free fatty acid (FFA) uptake into visceral adipose tissue is enhanced compared to abdominal subcutaneous tissue in vivo. Abdominal adipose tissue FFA uptake was measured using positron emission tomography (PET) and [(18)F]-labeled 6-thia-hepta-decanoic acid ([(18)F]FTHA) and fat masses using magnetic resonance imaging (MRI) in 18 healthy young adult males. We found that FFA uptake was 30% higher in visceral compared to subcutaneous adipose tissue (0.0025 +/- 0.0018 vs. 0.0020 +/- 0.0016 micromol/g/min, P = 0.005). Visceral and subcutaneous adipose tissue FFA uptakes were strongly associated with each other (P < 0.001). When tissue FFA uptake per gram of fat was multiplied by the total tissue mass, total FFA uptake was almost 1.5 times higher in abdominal subcutaneous than in visceral adipose tissue. In conclusion, we observed enhanced FFA uptake in visceral compared to abdominal subcutaneous adipose tissue and, simultaneously, these metabolic rates were strongly associated with each other. The higher total tissue FFA uptake in subcutaneous than in visceral adipose tissue indicates that although visceral fat is active in extracting FFA, its overall contribution to systemic metabolism is limited in healthy lean males. Our results indicate that subcutaneous, rather than visceral fat storage plays a more direct role in systemic FFA availability. The recognized relationship between abdominal visceral fat mass and metabolic complications may be explained by direct effects of visceral fat on the liver.

Contribution of glucose tolerance and gender to cardiac adiposity.

CONTEXT AND OBJECTIVE: To examine whether pericardial and myocardial fat depots may contribute to the association between diabetes and cardiovascular risk, including sex-related differences, and the role of adiponectin, we evaluated data in patients with obesity and without diabetes [nondiabetic (ND)] or with impaired glucose tolerance or type 2 diabetes and in lean ND controls. METHODS: Magnetic resonance imaging and spectroscopy were used to measure left ventricular (LV) function and abdominal sc and visceral fat areas to estimate respective masses, pericardial fat depots, and myocardial triglyceride content in 53 subjects (10 lean ND, 25 obese ND, six impaired-glucose-tolerance, and 12 type 2 diabetic patients with macrovascular disease); gender effects and adiponectin levels were evaluated in the available subset of subjects. RESULTS: Myocardial and pericardial fat increased progressively across study groups. They were lower in obese women than men (P = 0.002), but cardiac steatosis caught up in hyperglycemic women (+81% vs. ND, P = 0.01). Adiponectin was inversely related with both fat depots (P < 0.01) and LV mass (P = 0.003) and positively with LV function (P = 0.03). In multiple regression analysis, myocardial and pericardial fat were independently related with plasma glucose levels, only pericardial fat mass was associated with visceral adiposity and myocardial fat with cardiac output and work. CONCLUSIONS: We conclude that glycemia, gender, adiponectin, and cardiac workload are associated with, and hyperglycemia and male gender are independent positive predictors of, heart adiposity. Once glucose tolerance becomes impaired, the evolution of cardiac steatosis is more pronounced in women.

Effect of caloric restriction on myocardial fatty acid uptake, left ventricular mass, and cardiac work in obese adults.

Obesity is associated with increased fatty acid uptake in the myocardium, and this may have deleterious effects on cardiac function. The aim of this study was to evaluate how weight loss influences myocardial metabolism and cardiac work in obese adults. Thirty-four obese (mean body mass index 33.7 +/- 0.7 kg/m(2)) but otherwise healthy subjects consumed a very low calorie diet for 6 weeks. Cardiac substrate metabolism and work were measured before and after the diet. Myocardial fatty acid uptake was measured in 18 subjects using fluorine-18-fluoro-6-thia-heptadecanoic acid and positron emission tomography, and myocardial glucose uptake was measured in 16 subjects using fluorine-18-2-fluoro-2-deoxyglucose. Myocardial structure and cardiac function were measured using magnetic resonance imaging. Consumption of the very low calorie diet decreased weight (-11.2 +/- 0.6 kg, p <0.0001). Myocardial fatty acid uptake decreased from 4.2 +/- 0.4 to 2.9 +/- 0.2 micromol/100 g/min (p <0.0001). Myocardial mass decreased by 7% (p <0.005), and cardiac work decreased by 26% (p <0.0001). Whole-body insulin sensitivity increased by 33% (p <0.01), but insulin-stimulated myocardial glucose uptake remained unchanged (p = 0.90). Myocardial triglyceride content decreased by 31% (n = 8, p = 0.076). In conclusion, weight reduction decreases myocardial fatty acid uptake in parallel with myocardial mass and cardiac work. These results show that the increased fatty acid uptake found in the hearts of obese patients can be reversed by weight loss.

The Pro12Ala polymorphism of the PPARgamma2 gene is associated with hepatic glucose uptake during hyperinsulinemia in subjects with type 2 diabetes mellitus.

The Ala12 allele of the peroxisome proliferator-activated receptor gamma gene (PPARG2) has been associated with reduced risk of type 2 diabetes mellitus (T2DM) and increased whole-body and skeletal muscle insulin sensitivity in nondiabetic subjects. The effect of the Pro12Ala polymorphism on tissue specific insulin sensitivity in subjects with T2DM has not been previously investigated. We studied the effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake (GU) in T2DM subjects, and the rates of hepatic GU in nondiabetic and T2DM subjects during hyperinsulinemia. Our study included 105 T2DM subjects whose whole-body, skeletal muscle, subcutaneous adipose tissue, and hepatic GUs were measured using (18)F-fluorodeoxyglucose and positron emission tomography during the hyperinsulinemic euglycemic clamp. Hepatic GU was also measured in 68 nondiabetic subjects. In obese (body mass index >or=27 kg/m(2)) subjects with T2DM, the rate of hepatic GU was 28% lower in subjects with the Pro12Pro genotype than in carriers of the Ala12 allele (P = .001); and a similar trend was observed in nondiabetic obese subjects (P = .137). No effect of the Pro12Ala polymorphism on the rates of whole-body, skeletal muscle, or subcutaneous adipose tissue GU was observed in T2DM subjects. We conclude that the Ala12 allele of PPARG2 is associated with higher hepatic GU in obese subjects with T2DM.

Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance.

OBJECTIVE: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity. HYPOTHESIS: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content. DESIGN: Thirty-four healthy obese subjects (body mass index, 33.7 +/- 8.0 kg/m(2)) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [(18)F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [(18)F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy. RESULTS: Subjects lost weight (11.2 +/- 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05). CONCLUSIONS: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.

Effects of weight loss on visceral and abdominal subcutaneous adipose tissue blood-flow and insulin-mediated glucose uptake in healthy obese subjects.

OBJECTIVE: Rapid weight loss with very-low-calorie diet (VLCD) is known to improve insulin sensitivity and decrease adipose tissue masses. The aim was to investigate the effects of VLCD on adipose tissue regional glucose uptake (rGU) and perfusion and their association with adipokines. RESEARCH DESIGN AND METHODS: Sixteen healthy obese (body mass index 33+/-1.1 kg/m(2)) subjects underwent VLCD for 6 weeks. RGU and perfusion were measured using [(18)F]-fluoro-deoxy-glucose, [(15)O]H(2)O and positron emission tomography. RESULTS: Blood-flow and rGU expressed per gram of adipose tissue were higher in visceral fat compared to abdominal subcutaneous fat (P<0.01 for both). Dieting decreased weight by 11+/-0.9 kg (P<0.0001). Visceral adipose fat decreased by 25% (P<0.001) and abdominal subcutaneous fat by 16% (P<0.001). Whole body insulin sensitivity increased by 33% (P<0.01). Perfusion of both fat depots decreased (P<0.001), while rGU remained unchanged. Among the adipokines, leptin and interleukin-6 levels seemed to be associated with abdominal subcutaneous and intra-abdominal adipose tissue insulin resistance but not with adipose tissue perfusion. CONCLUSIONS: Abdominal adipose tissue perfusion and rGU are not related in obesity. Rapid weight loss decreases perfusion through adipose tissue depots but has no influence on rGU demonstrating the 'sink' role of adipose tissue.

Quantification of liver perfusion with [(15)O]H(2)O-PET and its relationship with glucose metabolism and substrate levels.

BACKGROUND/AIMS: Hepatic perfusion plays an important role in liver physiology and disease. This study was undertaken to (a) validate the use of Positron Emission Tomography (PET) and oxygen-15-labeled water ([(15)O]H(2)O) to quantify hepatic and portal perfusion, and (b) examine relationships between portal perfusion and liver glucose and lipid metabolism. METHODS: Liver [(15)O]H(2)O-PET images were obtained in 14 pigs during fasting or hyperinsulinemia. Carotid arterial and portal venous blood were sampled for [(15)O]H(2)O activity; Doppler ultrasonography was used invasively as the reference method. A single arterial input compartment model was developed to estimate portal tracer kinetics and liver perfusion. Endogenous glucose production (EGP) and insulin-mediated whole body glucose uptake (wbGU) were determined by standard methods. RESULTS: Hepatic arterial and portal venous perfusions were 0.15+/-0.07 and 1.11+/-0.34 ml/min/ml of tissue, respectively. The agreement between ultrasonography and [(15)O]H(2)O-PET was good for total and portal liver perfusion, and poor for arterial perfusion. Portal perfusion was correlated with EGP (r=or+0.62, p=0.03), triglyceride (r=or+0.66, p=0.01), free fatty acid levels (r=or+0.76, p=0.003), and plasma lactate levels (r=or-0.81, p=0.0009). CONCLUSIONS: Estimates of liver perfusion by [(15)O]H(2)O-PET compared well with those by ultrasonography. The method allowed to predict portal tracer concentrations which is essential in human studies. Portal perfusion may affect liver nutrient handling.

Brain white matter expansion in human obesity and the recovering effect of dieting.

CONTEXT AND OBJECTIVE: Obesity is associated with several metabolic abnormalities. Recent studies suggest that obesity also affects brain function and is a risk factor for some degenerative brain diseases. The objective of this study was to examine the effects of weight gain and weight loss on brain gray and white matter structure. We hypothesized that possible differences seen in the brains of obese subjects would disappear or diminish after an intensive dieting period. METHODS: In part I of the study, we scanned with magnetic resonance imaging 16 lean (mean body mass index, 22 kg/m(2)) and 30 obese (mean body mass index, 33 kg/m(2)) healthy subjects. In part II, 16 obese subjects continued with a very low-calorie diet for 6 wk, after which they were scanned again. Regional brain white and gray matter volumes were calculated using voxel-based morphometry. RESULTS: White matter volumes were greater in obese subjects, compared with lean subjects in several basal brain regions, and obese individuals showed a positive correlation between white matter volume in basal brain structures and waist to hip ratio. The detected white matter expansion was partially reversed by dieting. Regional gray matter volumes did not differ significantly in obese and lean subjects, and dieting did not affect gray matter. CONCLUSIONS: The precise mechanism for the discovered white matter changes remains unclear, but the present study demonstrates that obesity and dieting are associated with opposite changes in brain structure. It is not excluded that white matter expansion in obesity has a role in the neuropathogenesis of degenerative brain diseases.

Biodistribution of the fatty acid analogue 18F-FTHA: plasma and tissue partitioning between lipid pools during fasting and hyperinsulinemia.

UNLABELLED: Alterations of free fatty acid (FA) metabolism in several organs are implicated in the pathogenesis of chronic disorders. The aim of this study was to investigate the biodistribution and partitioning of the FA analog, 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic acid ((18)F-FTHA), across different lipid pools in plasma and in metabolically important organs and its response to insulin. METHODS: Eight anesthetized pigs were studied during fasting or euglycemic insulin stimulation. Plasma samples from the carotid artery, hepatic vein, and portal vein were collected at 10 and 40 min after (18)F-FTHA injection via indwelling catheters. The animals were then sacrificed and tissue biopsies rapidly obtained from the heart, brain, liver, subcutaneous and visceral fat, pancreas, intestine, and skeletal muscle. Radioactivity was assessed in the FA, phospholipid, and triglyceride or glycerol ester pools. RESULTS: The tissue-to-plasma intact (18)F-FTHA ratio was high in all tissues, with the highest values being in the heart and liver; (18)F-FTHA accumulated in the brain to a significant extent. Hyperinsulinemia was associated with higher plasma (18)F-FTHA clearance (P < 0.05) and lower labeled triglyceride appearance (P

Quantification of liver glucose metabolism by positron emission tomography: validation study in pigs.

BACKGROUND & AIMS: The liver is inaccessible to organ balance measurements in humans. To validate [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [(18)F]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual). METHODS: Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with C(15)O (blood pool) and [(18)F]FDG (glucose uptake). 6,6-Deuterated glucose ([(2)H]G) was coinjected with [(18)F]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [(18)F]FDG versus [(18)F]FDG-6-phosphate and [(18)F]-glycogen. Endogenous glucose production was measured with [(2)H]G and hepatic blood flow by flowmeters. RESULTS: HGU was increased in hyperinsulinemia versus fasting (P < .05). Fractional extraction of [(18)F]FDG and [(2)H]G was similar (not significant), intercorrelated (r = 0.98, P < .0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P < .0001), with a modest underestimation of HGU by the former. CONCLUSIONS: [(18)F]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [(18)F]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.

Myocardial triglyceride content and epicardial fat mass in human obesity: relationship to left ventricular function and serum free fatty acid levels.

CONTEXT AND OBJECTIVE: Ectopic fat accumulation within and around the myocardial wall has been implicated in the pathogenesis of heart disease in obesity. We evaluated myocardial and epicardial fat, left ventricular (LV) function, and metabolic risk factors in nine (five lean, four moderately obese) men. METHODS: Myocardial fat percent was quantified in the septum by proton magnetic resonance spectroscopy. Reproducibility was assessed by triplicate systolic and diastolic measurements. LV parameters and epicardial fat were determined by magnetic resonance imaging. Waist-to-hip ratio and liver enzymes (alanine transaminase) were used as surrogate markers of visceral and liver fat contents. RESULTS: Myocardial fat (2.1 +/- 0.5 vs. 0.8 +/- 0.1, P = 0.03) and epicardial fat (120 +/- 33 vs. 55 +/- 12 g, P = 0.08) were higher in obese than lean subjects. Individuals with above-median alanine transaminase values had a 4-fold elevation in myocardial fat. The coefficient of variation of repeated myocardial fat percent determinations was 17 +/- 3 and 23 +/- 3% in systole and diastole, respectively. Myocardial fat was correlated with free fatty acid (FFA) levels (r = 0.76; P = 0.017), epicardial fat (r = 0.69; P = 0.042), and waist-to-hip ratio (r = 0.70; P = 0.035), and it showed a tendency to associate positively with LV work. Epicardial fat was associated with peripheral vascular resistance (positively) and the cardiac index (negatively). FFA levels were significantly correlated with LV mass (r = 0.72; P = 0.030) and forward work (r = 0.74; P = 0.023). CONCLUSIONS/INTERPRETATION: The accumulation of triglyceride in and around the myocardium of moderately obese individuals is significant, and it is related to FFA exposure, generalized ectopic fat excess, and peripheral vascular resistance. These changes precede LV overload and hypertrophy.

18F-FDG assessment of glucose disposal and production rates during fasting and insulin stimulation: a validation study.

UNLABELLED: The glucose analog (18)F-FDG is commonly used to quantify regional glucose uptake in vivo. The aim of this study was to test whether the analysis of plasma (18)F-FDG kinetics could be used to estimate endogenous glucose production (EGP) and the total rate of appearance (Ra), total rate of disappearance (Rd), and the metabolic clearance rate (MCR) of glucose. METHODS: Fourteen pigs were coinjected with (18)F-FDG and 6,6-(2)H-glucose ((2)H-G) during fasting (n = 6) and during physiologic (1.0 mU.kg(-1).min(-1), n = 4) and supraphysiologic (5.0 mU.kg(-1).min(-1), n = 4) euglycemic hyperinsulinemia. Arterial plasma was sampled for 180 min to quantify the parameters for the 2 tracers. RESULTS: Fasting Rd((2))(H-G) and Rd(FDG) were 12.3 +/- 2.1 and 13.3 +/- 1.3 micromol.kg(-1).min(-1) (difference not statistically significant [NS]). M values were more than doubled between the 2 clamp studies (P < 0.0001). Rd((2))(H-G) and Rd(FDG) were dose-dependently higher during the hyperinsulinemic state (19.8 +/- 3.7 vs. 18.9 +/- 1.1 and 31.4 +/- 4.1 vs. 31.9 +/- 2.3 in 1.0 and 5.0 mU.kg(-1).min(-1) studies, respectively; difference between tracers NS) than during the fasting state, with a parallel suppression of EGP((2))(H-G) and EGP(FDG). Parameters estimated by (18)F-FDG and (2)H-G were equivalent in all groups; their agreement was confirmed by Bland-Altman examination. Total Rd(FDG) correlated with Rd((2))(H-G) (r = 0.74; P = 0.003), M (r = 0.92; P = 0.001), MCR((2))(H-G) (r = 0.52; P = 0.037), and EGP((2))(H-G) (r = -0.71; P = 0.004). EGP(FDG) correlated with EGP((2))(H-G) (r = 0.62; P = 0.018), Rd((2))(H-G) (r = -0.78; P = 0.001), and MCR((2))(H-G) (r = -0.67; P = 0.008). The (18)F-FDG mean transit time correlated inversely with the M and Rd values and positively with EGP. CONCLUSION: The glucose analog (18)F-FDG can be used in the simultaneous estimation of whole-body glucose turnover and production and regional (18)F-FDG PET measurements under both fasting and insulin-stimulated conditions.

[11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia.

PURPOSE: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [11C]palmitate injection during fasting and insulin stimulation. METHODS: Plasma [11C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. RESULTS: At 10 min, plasma levels of unchanged [11C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P< or=.03), suggesting faster clearance. Levels of unmetabolized [11C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [11C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92+/-1% and 82+/-6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. CONCLUSION: The study indicates that the redistribution of [11C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional [11C]palmitate source in the modeling of PET data.