Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.

BACKGROUND: Changes in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, diffuse optical spectroscopic imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties. METHODS: Ten overweight or obese adults were assessed during 3 months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed-effects models and were also used to form 3D surface images. RESULTS: Subjects lost a mean of 11.7±3.4% of starting weight, while significant changes in A (+0.23±0.04 mm(-1), adj. P<0.001),b (-0.17±0.04, adj. P<0.001), tissue water fraction (+7.2±1.1%, adj. P<0.001) and deoxyhemoglobin (1.1±0.3 µM, adj. P<0.001) were observed using mixed-effect model analysis. DISCUSSION: Optical scattering signals reveal alterations in tissue structure that possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.

Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes.

Recent technical advances allow detection of several hundred volatile organic compounds (VOCs) in human exhaled air, many of which reflect unidentified endogenous pathways. Our group has previously estimated plasma glucose levels in healthy adults during a standard oral glucose tolerance test via exhaled VOC analysis. As a result of the metabolic characteristics of hyperglycemia in the diabetic (low insulin and increased free fatty acids and ketones), we hypothesized that different exhaled VOC profiles may be present in children with type 1 diabetes mellitus (T1DM) during spontaneous hyperglycemia. Exhaled methyl nitrate strongly correlated specifically with the acute, spontaneous hyperglycemia of T1DM children. Eighteen experiments were conducted among 10 T1DM children. Plasma glucose and exhaled gases were monitored during either constant euglycemia (n = 5) or initial hyperglycemia with gradual correction (n = 13); all subjects received i.v. insulin and glucose as needed. Gas analysis was performed on 1.9-liter breath samples via gas chromatography using electron capture, flame ionization, and mass selective detection. Among the approximately 100 measured exhaled gases, the kinetic profile of exhaled methyl nitrate, commonly present in room air in the range of 5-10 parts per trillion, was most strongly statistically correlated with that of plasma glucose (P = 0.003-0.001). Indeed, the kinetic profiles of the two variables paralleled each other in 16 of 18 experiments, including repeat subjects who at different times displayed either euglycemia or hyperglycemia.

Effect of prior hyperglycemia on IL-6 responses to exercise in children with type 1 diabetes.

The proinflammatory cytokine interleukin-6 (IL-6) may modulate the onset and progression of complications of diabetes. As this cytokine increases after exercise, and many other exercise responses are altered by prior glycemic fluctuations, we hypothesized that prior hyperglycemia might exacerbate the IL-6 response to exercise. Twenty children with type 1 diabetes (12 boys/8 girls, age 12-15 yr) performed 29 exercise studies (30-min intermittent cycling at approximately 80% peak O2 uptake). Children were divided into four groups based on highest morning glycemic reading [blood glucose (BG) < 150, BG 151-200, BG 201-300, or BG > 300 mg/dl]. All exercise studies were performed in the late morning, after hyperglycemia had been corrected and steady-state conditions (plasma glucose < 120 mg/dl, basal insulin infusion) had been maintained for > or = 90 min. Blood samples for IL-6, growth factors, and counterregulatory hormones were drawn at pre-, end-, and 30 min postexercise time points. At all time points, circulating IL-6 was lowest in BG < 150 and progressively higher in the other three groups. The exercise-induced increment also followed a similar dose-response pattern (BG < 150, 0.6 +/- 0.2 ng/ml; BG 151-200, 1.2 +/- 0.8 ng/ml; BG 201-300, 2.1 +/- 1.1 ng/ml; BG > 300, 3.2 +/- 1.4 ng/ml). Other measured variables (growth hormone, IGF-I, glucagon, epinephrine, cortisol) were not influenced by prior hyperglycemia. Recent prior hyperglycemia markedly influenced baseline and exercise-induced levels of IL-6 in a group of peripubertal children with type 1 diabetes. While exercise is widely encouraged and indeed often considered part of diabetic management, our data underscore the necessity to completely understand all adaptive mechanisms associated with physical activity, particularly in the context of the developing diabetic child.