Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity.

CONTEXT: Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive. OBJECTIVE: We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals. DESIGN AND PARTICIPANTS: Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m(2) · min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Musclesen and those in the lower two tertiles were assigned Muscleres. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liversen and the remainder Liverres. MAIN OUTCOMES MEASURES: Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared. RESULTS: Musclesen and Muscleres had similar body mass index and total fat (P > .16), but Musclesen had lower glycated hemoglobin (P < .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Musclesen had lower visceral (P < .001) and liver (P < .001) fat. Liversen had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liverres. When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1-hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity. CONCLUSIONS: Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity.

Detection of changes in cartilage water content using MRI T2-mapping in vivo.

OBJECTIVES: Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vivo if changes in the water content of patellar cartilage typically occurring in early OA can be detected using T(2) mapping MRI methods. DESIGN: Twenty healthy volunteers performed 60 knee bends in order to compress their patellar cartilage thereby reducing its water content. MR images of the patellar cartilage were acquired immediately following exercise and after 45 min of rest. Patellar cartilage thickness and T(2) maps were determined and their difference between the time points evaluated. RESULTS: Cartilage thickness increased by 5.4+/-1.5% from 2.94+/-0.15 mm to 3.10+/-0.15 mm (P< 0.001) following 45 min of rest, while T(2) increased by 2.6+/-1.0% from 23.1+/-0.5 ms to 23.7+/-0.6 ms (P< 0.05). CONCLUSION: Small, physiologic changes in the water content of patellar cartilage and the concomitant change in proteoglycan and collagen density following exercise can be detected using MRI. The proposed T(2)-mapping method, together with other non-invasive MR cartilage imaging techniques, could aid in the early diagnosis of OA.

Metabolite and water apparent diffusion coefficients in the isolated rat heart: effects of ischemia.

A decrease in the apparent diffusion coefficient (ADC) of water is important in the detection of acute brain disorders, yet it is unknown whether changes in myocardial ADCs hold similar potential. Consequently, in this study a STEAM pulse sequence was modified in order to measure the ADCs of water and the (1)H-NMR detectable metabolites, taurine (an inert marker) and creatine, during perfusion, ischemia, and reperfusion in the isolated rat heart. At the short diffusion time of 50 ms, myocardial ADCs were (1.06 +/- 0. 07) x 10(-3) mm(2)/s for water, (0.29 +/- 0.01) x 10(-3) mm(2)/s for taurine and (0.26 +/- 0.01) x 10(-3) mm(2)/s for creatine. Heart water and taurine ADCs remained constant during ischemia, yet the total creatine ADC increased by 35% owing to the hydrolysis of PCr to creatine. The average cardiomyocyte diameter, calculated from taurine ADC values measured at diffusion times between 50 ms and 1510 ms, was 40 microm in the perfused heart and 27 microm by the end of ischemia. It is concluded that the taurine ADC measured at short diffusion times does not reveal ischemic injury in the heart, but at long diffusion times may be used to calculate changes in myocyte diameter. Magn Reson Med 44:208-214, 2000.