Raj K. Krishnan

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high-risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in 23 older, obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin, and basal fat oxidation were greater in the hypocaloric group. Following the intervention, there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007) but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved but that such a trend may rely on reducing caloric intake in addition to exercise training.

Effects of Exercise and Caloric Restriction on Insulin Resistance and Cardiometabolic Risk Factors in Older Obese Adults—A Randomized Clinical Trial

BACKGROUND The prevalence of insulin resistance, metabolic syndrome, and cardiovascular disease is greatest in older obese patients, and effective evidence-based treatment strategies are lacking. METHODS A prospective controlled study was conducted on 24 older (65.5 +/- 5.0 years) obese (body mass index, 34.3 +/- 5.2 kg/m(2)) adults with clinically diagnosed metabolic syndrome. We examined the effect of exercise alone (EX) or exercise combined with moderate caloric restriction (-500 kcal, EX + CR) on metabolic and cardiovascular risk factors. Measures of insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and by oral glucose tolerance test, lipid profiles, blood pressure, body composition, abdominal fat, and aerobic capacity were all obtained before and after the interventions. RESULTS Both groups experienced significant weight loss, but the reduction was greater in the EX + CR group than in the EX group (-6.8 +/- 2.7 kg vs -3.7 +/- 3.4 kg, respectively, p = .02). Both interventions improved insulin sensitivity (2.4 +/- 2.4 mg/kg FFM/min and 1.4 +/- 1.7 mg/kgFFM/min, respectively, p < .001) and indices of metabolic syndrome (systolic/diastolic blood pressure, waist circumference, glucose, and triglycerides; p < .05). High-density lipoprotein levels remained unchanged. Total abdominal, subcutaneous, and visceral fat; aerobic capacity; and total and low-density lipoprotein cholesterol were also improved. With the exception of weight loss and subcutaneous fat, there was no difference in the magnitude of improvement between the interventions. CONCLUSION These data suggest that exercise alone is an effective nonpharmacological treatment strategy for insulin resistance, metabolic syndrome, and cardiovascular disease risk factors in older obese adults.

Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans

To examine the effects of acute altitude-induced hypoxia on the hormonal and metabolic response to ingested glucose, 8 young, healthy subjects (5 men and 3 women; age, 26 +/- 2 years; body mass index, 23.1 +/- 1.0 kg/m(2)) performed 2 randomized trials in a hypobaric chamber where a 75-g glucose solution was ingested under simulated altitude (ALT, 4300 m) or ambient (AMB, 362 m) conditions. Plasma glucose, insulin, C-peptide, epinephrine, leptin, and lactate concentrations were measured at baseline and 30, 60, 90, and 120 minutes after glucose ingestion during both trials. Compared with AMB, the plasma glucose response to glucose ingestion was reduced during the ALT trial (P = .04). There were no differences in the insulin and C-peptide responses between trials or in insulin sensitivity based on the homeostasis model assessment of insulin resistance. Epinephrine and lactate were both elevated during the ALT trial (P < .05), whereas the plasma leptin response was reduced compared with AMB (P < .05). The data suggest that the plasma glucose response is suppressed at ALT, but this is not due to insulin per se because insulin and C-peptide levels were similar for both trials. Elevated plasma epinephrine and lactate during ALT are indicative of increased glycogenolysis, which may have masked the magnitude of the reduced glucose response. We conclude that, during acute altitude exposure, there is a rapid metabolic response that is accompanied by a shift in the hormonal milieu that appears to favor increased glucose utilization.

Age-related differences in the pancreatic β-cell response to hyperglycemia after eccentric exercise

Eccentric exercise (ECC) causes muscle damage, insulin resistance, and increased pancreatic β-cell secretion in young individuals. However, the effects of age on the pancreatic β-cell response to glucose after ECC are unknown. Hyperglycemic clamps (180 min, 10.0 mM) were performed on eight young (age 22 ± 1 yr) and eight older (age 66 ± 2 yr) healthy sedentary males without exercise (CONT) and 48 h after ECC. ECC increased ( P < 0.02) muscle soreness ratings and plasma creatine kinase concentrations in both groups. Insulin and C-peptide secretions were similar between young and older subjects during CONT clamps. ECC increased ( P < 0.05) first-phase (0-10 min) C-peptide area under the curve in young (4.2 ± 0.4 vs. 3.7 ± 0.6 nM ⋅ min; ECC vs. CONT, respectively) but not in older subjects (3.2 ± 0.7 vs. 3.5 ± 0.7 nM ⋅ min; ECC vs. CONT), with significant group differences ( P < 0.02). Indeed, ECC repressed ( P < 0.05) first-phase peak C-peptide concentrations in older subjects (0.93 ± 0.16 vs. 1.12 ± 0.11 nM; ECC vs. CONT). Moreover, first-phase C-peptide-to-insulin molar ratios suggest age-related differences ( P < 0.05) in insulin/C-peptide clearance after ECC. Furthermore, the observed C-peptide response after ECC was related to abdominal adiposity [ r = -0.62, P < 0.02, and r = -0.66, P < 0.006, for first and second (10-180 min) phases, respectively]. In conclusion, older individuals did not exhibit the compensatory increase in β-cell secretion observed among young individuals after ECC. Thus, with increasing age, the pancreatic β-cell may be less responsive to the physiological stress associated with ECC.

A High Glycemic Meal Suppresses the Postprandial Leptin Response in Normal Healthy Adults

Background/Aims: To evaluate the metabolic effects of meals with varying glycemic index (GI). Methods: We measured the glucose, insulin and leptin responses to two contrasting breakfast cereals in a group of 10 young healthy volunteers. Meals were provided on two separate occasions in random order after a 12-hour overnight fast, and consisted of 50 g of available carbohydrate from either Corn Flakes (Kellogg’s), or Fiber One® (General Mills). Blood samples were obtained at rest, and 30, 60, 90 and 120 min after eating. The GI was calculated from the glucose response to the test meal normalized against a 50 g oral glucose load. Results: The GI for Corn Flakes was 125 ± 17 units and 49 ± 8 units for Fiber One®. These meals were classified as high GI and low GI, respectively, and were significantly different from each other (p < 0.0003). The area under the insulin response curve (AUC) following the low glycemic meal was significantly attenuated compared to the high glycemic meal (14,064 ± 2,694 vs. 6,828 ± 1,182 pmol/l·min, p < 0.02). The leptin AUC revealed that circulating leptin was suppressed by the high glycemic meal compared to the low (3.1 ± 1.5 vs. 9.6 ± 3.6 ng/ml·min, p < 0.04). Conclusions: Lower insulin and higher leptin suggests that low glycemic meals promote a postprandial metabolic milieu that is favorable for reduced food consumption; this may be advantageous in the control of obesity and related disorders including insulin resistance and type 2 diabetes.

Acknowledgement to the 2007 Reviewers

T. Decsi, Pécs, Hungary K.A. Dewaal, Zwolle, The Netherlands I. Dostalova, Prague, Czeck Republic C.P. Earthman, St. Paul, USA P. Eckl, Salzburg, Austria K. Eder, Halle/Saale, Germany I. Elmadfa, Vienna, Austria G. Emil, Bratislava, Republic of Slovakia M. Faber, Tygerberg, South Africa E. Fabian, Vienna, Austria L. Ferguson, Auckland, New Zealand A. Flynn, Cork, Ireland S.D. Freedman, Boston, USA J. Freeland-Graves, Austin, USA H. Freisling, Vienna, Austria J. Frohlich, Vancouver, Canada D. Fuchs, Innsbruck, Austria N. Fuller, London, UK P. Galassetti, Calif., USA K. Gedrich, Freising-Weihenstephan, Germany D. Genser, Vienna, Austria H. Goldenberg, Vienna, Austria R. Grossklaus, Berlin, Germany F. Guillon, Nantes, France P. Haber, Vienna, Austria J.E. Haddow, Providence, USA M.H. Hamdaoui, Tunis, Tunisia J.C. Hansen, Aarhus, Denmark H. Hauner, Munich, Germany S. Hercberg, Bobigny, France M. Hershfinkel, Be’er-Sheva, Israel H. Heseker, Paderborn, Germany M. Hiesmayr, Vienna, Austria E.C. Hinton, Cambridge, UK M. Hohenegger, Vienna, Austria B.J. Holub, Guelph, Canada N. Houalla, Beirut, Lebanon G. Hu, Helsinki, Finland M. Huettinger, Vienna, Austria T. Inagawa, Izumo, Japan C. Invitti, Milan, Italy S. Jackson, London, UK G. Jahreis, Jena, Germany A. Kafatos, Heraklion, Greece H. Karlic, Vienna, Austria C.L. Keen, Davis, USA M.J. Keenan, Baton Rouge, USA R. Kelishadi, Isfahan, Iran D. Kelley, California, USA E.T. Kennedy, Boston, USA V.G. Athyros, Thessaloniki, Greece S. Lee, Seoul, Korea W. Aberer, Graz, Austria F.B. Aksungar, Istanbul, Turkey L. Allen, Davis, USA S.B. Astley, Colney, UK P. Athias, Dijon, France K.T. Augusti, Thalassery, India F. Azizi, Tehran, Iran P. Balagopal, Jacksonville, USA D.E. Barre, Sydney, Canada R.L. Batterham, London, UK I. Bautista, Las Palmas de Gran Canaria, Spain H. Bays, Louisville, USA R. Benamouzig, Bobigny, France A. Berg, Freiburg, Germany J. Berger, Vienna, Austria E. Oerich Berghofer, Vienna, Austria R. Bergmann, Berlin, Germany L.M. Bermejo López, Madrid, Spain V. Boehm, Jena, Germany H. Boeing, Nuthetal, Germany A. Bordoni, Bologna, Italy C.L. Bowlus, Sacramento, USA J. Bradbury, London, UK M.A. Brehm, Amsterdam, The Netherlands J. Briedé, Maastricht, The Netherlands T.L. Broderick, Glendale, USA C. Brombach, Wädenswil, Switzerland D.L. Brown, Ithaca, USA R.S. Bruno, Storrs, USA W. Bursch, Vienna, Austria P.C. Calder, Southampton, UK J. Campion, Pamplona, Spain M. Caroli, Brindisi, Italy R. Cermak, Leipzig, Germany N. Chang, Seoul, Korea J.-M. Chardigny, Clermont-Ferrand, France M.-F. Chen, Taipei, Taiwan S. Claeyssens, Rouen, France F. Correia, Porto, Portugal T. Crowe, Melbourne, Australia E. Curis, Paris, France S. Czernichow, Bobigny, France H. Dabadie, Pessac, France S. Dalton, New York, USA U. Das, Willemstad, Curacao, Neerlandaises Antilles M. Daniel Vaz de Almeida, Porto, Portugal J. de la Osada, Zaragoza, Spain D. de Luis, Simancas, Spain