Search

Objective: This study examined the metabolic effects of heart transplantation in patients in end-stage cardiac failure.Research Design and Methods: A total of 18 patients after heart transplantation for end-stage heart disease (age 47 +/- 3 years; transplant age 5.5 +/- 1.5 years; BMI 25.8 +/- 0.8 kg/m(2); cyclosporin A 4.2 +/- 0.6 mg/[kg.day]; azathioprine 0.87 +/- 0.31 mg/[kg.day]), 12 patients with type 2 diabetes (D-Tx), and 6 patients without type 2 diabetes (Tx) were studied by means of 1) an oral glucose tolerance test (OGTT) to assess the beta-cell secretory response, 2) a euglycemic-hyperinsulinemic (1 mU/[kg.min]) clamp combined with indirect calorimetry and a primed continuous infusion of [6,6-2H2]glucose and [1-13C]leucine to measure postabsorptive and insulin-stimulated carbohydrate and protein metabolism, and 3) 1H-NMR spectroscopy of the calf muscles to measure intramyocellular triglyceride (IMCL) content. The patients were selected from 480 transplant patients in whom there was a 6% prevalence of type 2 diabetes. Five healthy subjects matched for anthropometric parameters served as control subjects (CON).Results: Tx had postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism, as well as IMCL content, similar to that of CON. D-Tx were characterized by a reduced secretory response during the OGTT and peripheral insulin resistance with respect to glucose metabolism, which was paralleled by increased plasma free fatty acid concentrations and IMCL content. A defective insulin-dependent suppression of the endogenous leucine flux (index of proteolysis) was also evident during the clamp in D-Tx.Conclusions: Heart transplantation, notwithstanding the immunosuppressive therapy, was characterized by a normal postabsorptive and insulin-stimulated glucose, leucine, and free fatty acid metabolism in Tx. In contrast, insulin resistance with respect to glucose, free fatty acids, and protein metabolism was present in D-Tx regardless of whether diabetes was preexisting or consequent to heart transplantation. [ABSTRACT FROM AUTHOR]

Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states. [ABSTRACT FROM AUTHOR]

Studies have pointed to insulin resistance as pathogenic factor in fatty liver; the role of beta-cell function, even if generally accepted, is unexplored. This study was undertaken to test whether fasting indexes of beta-cell function were related to the intra-hepatic fat (IHF) content in non-diabetic humans. IHF content was measured by means of ¹H-Magnetic Resonance Spectroscopy (MRS), and insulin sensitivity and beta-cell function were estimated based on fasting plasma glucose, insulin and C-peptide in 31 patients with fatty liver and 62 individuals with matched anthropometric features (age: 36±8 vs. 36±7 years, BMI: 27.4±3.8 vs. 26.7±3.2 kg/m²). Patients with fatty liver had higher fasting glucose (P<0.05), insulin (P<0.01), c-peptide (P<0.005) and insulin resistance (HOMA2-%S: 56±24% vs. 77±38%; P=0.008). Fasting insulin secretion (383±168 vs. 284±107 pmol/L; P=0.007) and the beta-cell insulin sensitivity (HOMA2-%B: 171 ± 41% vs. 152±43%; P=0.04) were also increased in patients with fatty liver. A subgroup analysis, performed matching also for HOMA2-%S (including only those <70%; n=25 and n=30 in subjects with and without fatty liver: 47±12% vs. 49±12; P=0.56), confirmed increased insulin secretion (408±178 vs. 266±107 pmol/L; P=0.002) and HOMA2-%B (174±62% ys. 136±56%; P=0.02) in the individuals with fatty liver. In univariate analysis including the entire population fasting insulin explained 14% of the IHF content variability (P<0.000); in multivariate analysis the inclusion of fasting C-peptide increased it more than two-fold (to 32%; P<0.000); inclusion of age, sex, BMI and glucose in this model was not useful. Logistic regression showed that the insulin*C-peptide product was associated with the likelihood of having fatty liver (P<0.001). In conclusion, nondiabetic individuals with fatty liver are characterized not only by reduced insulin sensitivity but also by features of enhanced fasting beta-cell function, which is an independent meaningful factor. [ABSTRACT FROM AUTHOR]

Fatty liver is characterized by metabolic abnormalities at the liver site but also at the level of the skeletal muscle and adipose tissue. In patients with overt type 2 diabetes fatty liver is associated with impaired insulin-stimulated myocardial glucose uptake and reduced coronary functional capacity. To ascertain whether fatty liver is associated with alterations of cardiac energy metabolism also before the development of overt diabetes, we studied 21 young, non-diabetic men with fatty liver and 21 healthy men matched for anthropometric features (age: 35±7 vs. 36±7 years, BMI: 27.5±3.6 vs. 27.1±1.3 kg/m²) in the resting state by means of cardiac Magnetic Resonance Imaging (MRI), ³P spectroscopy (MRS) and hepatic ¹H-MRS to assess respectively the cardiac morphology and function, the left ventricular (LV) energy metabolism and the IHF content as a continuous variable. Insulin sensitivity (HOMA2-%S) and B-cell insulin sensitivity (HOMA2-%B) were determined by the updated HOMA computer model. Individuals with fatty liver showed reduced insulin sensitivity (HOMA2-%S: 51±19% vs. 63±18%; P<0.05), abnormal serum triglycerides (1.85±1.20 vs. 1.00±0.49 mmol/L; P<0.02), FFA (711 ± 194 vs. 559±184 mmol/L; P<0.01) and adipokines concentrations (lower plasma adiponectin and resistin concentrations) and higher blood pressure. Parameters of LV morphology (mass and volumes), systolic function (ejection fraction, stroke volume) and diastolic function (early/atrial peak filling rates and deceleration time) were not different between groups. The LV phosphocreatine (PCr)/ATP ratio, which is a recognized marker of cardiac high energy phosphates metabolism, was significantly reduced in patients with fatty liver (defined as IHF content >5% wet weight) in comparison with normals (1.85±0.35 vs. 2.11± 0.31 mean ± SD; P<0.016) and was proportionally linked with diastolic blood pressure (Spearman's rho: r=0.41, P<0.02). In conclusion, despite of normal LV morphologic features and systolic and diastolic functions, abnormal LV energy metabolism may be detected in non-diabetic patients with fatty liver. Even if within the normal range, higher blood pressure may be contributing to this cardiac metabolic alteration. [ABSTRACT FROM AUTHOR]

This study examined the impact of L-acetylcamitine therapy in patients with lipodystrophy syndrome consequent to the effect of antiretroviral therapy in human immunodeficiency virus (HIV) on insulin sensitivity and body composition. Seven HIV-1 patients with lipodystrophy syndrome (3 females/4 males, age = 40 ± 4 yr, HIV duration = 8 ± 2 yr, BMI = 23.7 ± 3.2 kg/m², on protease inhibitors and nucleoside analog reverse transcriptase inhibitors) were studied. In all patients, the following parameters were evaluated before and after 32 weeks of therapy with L-acetylcarnitine (2g/day): fasting glucose and insulin levels (to calculate HOMA-IS and QUICKI), lipid profile, lipid oxidation (indirect calorimetry), body composition (DEXA) and intramyocellular triglyceride (IMCL) content of the calf muscles (¹H-NMR spectroscopy). After treatment with L-acetylcarnitine insulin sensitivity improved (HOMA-IS from 0.56±0.30 to 0.97±0.45 and QUICKI from 3.40±0.13 to 3.86±0.16; both p<0.05). L-acetylcarnitine, caused a decrease of IMCL content of the soleus muscle (from 206 ± 99 to 80 ± 43 AU; P = 0.005), meanwhile it was unaffected at the level of tibialis anterior (from 28 ± 11 to 31 ± 10 AU, P = ns). L-acetylcarnitine treatment increased the percentage of fat in the legs (from 13.5% to 14.7%; p=0.005). The percentage fat in the mink and in the arms did not change (respectively from 25±2 to 24±1%, P = 0.08 and from 21±4 to 21±3%, P= 0.7). In parallel plasma FFA (0.78±0.29 vs 0.65±0.23 mmol/l; p< 0.05) and Respiratory Quotient (0.82±0.16 vs 0.74±0.15; p<0.05) decreased. Treatment with L-acetylcarnitine for 32 weeks in HIV-1 infected patients with lipodystrophy syndrome caused improvement of insulin sensitivity and of FFA metabolism. Most interestingly, the short-term treatment with L-acetylcarnitine determined an improvement of body fat distribution both at orthotopic and ectopic sites. [ABSTRACT FROM AUTHOR]