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Obesity is the most common cause of insulin resistance in children. The effect of different degrees of obesity in children on the prevalence of the metabolic syndrome and its relationship to insulin resistance is examined.

We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism. Twelve older men ([greater than or equal to] 60 yr) with serum total testosterone concentrations aging; muscle strength; lean body mass; insulin-like growth factor I

Background: Few studies have compared long-term moderate-intensity aerobic versus light-resistance training on serial improvements in glucose tolerance in older people. Methods: Healthy, inactive older (74 ± 5 [SD] years) women (N = 20) were randomized into either a high-volume, moderate-intensity aerobic (ATM, n = 12) or a lower-intensity resistance training (RTL, n = 8) group. Both groups exercised under supervision 4 times per week for 45- to 60-minute sessions over 9 months. Measurements of plasma glucose, insulin, and free fatty acid (FFA) responses to an oral glucose tolerance test (OGTT) were performed at baseline and at 3, 6, and 9 months 48 hours after the last exercise session. Results: We observed significant improvements in 2-hour glucose concentrations at 3, 6, and 9 months among women in the RTL (152 ± 42 vs 134 ± 33 vs 134 ± 24 vs 130 ± 27 mg · dL-1; P < .05), but not the ATM (151 ± 25 vs 156 ± 37 vs 152 ± 40 vs 155 ± 39 mg · dL-1) group. These improvements were accompanied by an 18% (P < .07) decrease in basal FFA concentrations in the RTL group, whereas basal and 30-minute FFA concentrations increased (P < .05) after training in the ATM group. Conclusions: These findings suggest that the net physiological benefits of exercise might have been blunted in the ATM group, owing to higher circulating levels of FFA, which might have temporarily interfered with insulin action. [ABSTRACT FROM AUTHOR]

When allowed to choose between different macronutrients, most animals display a strong attraction toward carbohydrates compared with proteins. It remains uncertain, however, whether this food selection pattern depends primarily on the sensory properties intrinsic to each nutrient or, alternatively, metabolic signals can act independently of the hedonic value of sweetness to stimulate elevated sugar intake. Here we show that Trpm5-/-mice, which lack the cellular mechanisms required for sweet and several forms of L-amino acid taste transduction, develop a robust preference for D-glucose compared with isocaloric L-serine independently of the perception of sweetness. Moreover, a close relationship was found between glucose oxidation and taste-independent nutrient intake levels, with animals increasing intake as a function of glucose oxidation rates. Furthermore, microdialysis measurements revealed nutrient-specific dopaminergic responses in accumbens and dorsal striatum during intragastric infusions of glucose or serine. Specifically, intragastric infusions of glucose induced significantly higher levels of dopamine release compared with isocaloric serine in both ventral and dorsal striatum. Intragastric stimulation of dopamine release seemed to depend on glucose utilization, because administration of an anti-metabolic glucose analog resulted in lower dopamine levels in striatum, an effect that was reversed by intravenous glucose infusions. Together, our findings suggest that carbohydrate-specific preferences can develop independently of taste quality or caloric load, an effect associated with the ability of a given nutrient to regulate glucose metabolism and stimulate brain dopamine centers. [ABSTRACT FROM AUTHOR]

Although metformin (MET) is an insulin sensitizer that is being used as an adjunct to treatment of some of the complications of childhood obesity besides T2DM, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance. To examine this question, we conducted a 3-month double-blind clinical trial in 28 obese (mean BMI: 40.3±5.7 kg/m:), insulin resistant (HOMA-IR: 7.6±2.8 and WBISI: 1.5±0.7) adolescents (age 15.0±1.3 yrs) randomized to MET (n=15, dose 1500 mg daily) or placebo (n=13). Treatment with MET was well tolerated and there were no adverse changes in liver functions, lactate or vitamin B12 levels. Post intervention, the MET group had a 35 % improvement of insulin sensitivity (WBISI) when compared to the Placebo group (p = 0.008, p[sup *] = 0.09). MET also decreased BMI (p and p[sup *] = 0.02) due to a reduction in subcutaneous fat (p and p[sup *] = 0.03) and deep superficial subcutaneous fat (p and p[sup *] = 0.04) as assessed by MRI. While there was no change in endothelial function, inflammatory cytokines and lipid parameters, cardiovascular fitness as assessed by heart rate recovery after exercise improved with MET and worsened in placebo (p =0.02, p[sup *] = 0.03). In conclusion short-term use of MET is well tolerated by obese children with normal glucose tolerance and has a beneficial effect on insulin sensitivity and BMI. Although biomarkers of cardiovascular disease were not altered, there was an unexpected improvement in cardiovascular fitness with MET treatment. Long-term trials are needed to determine whether MET may be a useful agent to prevent the progressive deterioration of glucose tolerance and to reduce the risk of future cardiovascular disease as obese youth mature unto young adulthood. (*) adjusted for differences at baseline. [ABSTRACT FROM AUTHOR]

Normal glucose tolerance is expressed over a wide range of glucose concentrations. Whether there is a continuum of risk for developing type 2 diabetes mellitus even when the 2-h plasma glucose is still within this normal range is uncertain. Oral glucose tolerance tests were performed in 407 obese normal glucose tolerance youth (4-20 yr) to examine the relationship between variations in 2-h plasma glucose levels and beta-cell responsiveness. Individuals were grouped by 2-h plasma glucose levels as follows: 1) less than 100 mg/dl, 2) 100-119 mg/dl, and 3) 120-139 mg/dl. Subsequent analysis stratified each 2-h plasma level by insulin sensitivity index. Increased 2-h glucose level was associated with a progressive increase in glucose between 0 and 30 min (P < 0.05). The Delta (0-30 min) insulin did not vary significantly across levels, thus resulting in a decreased insulinogenic index (P < 0.02). This pattern was observed at every level of insulin sensitivity (P < 0.02). These data translated to an unfavorable (leftward) shift in the insulin feedback system for increasing 2-h glucose level (P < 0.005). Increased 2-h plasma glucose within the range of normal glucose tolerance in obese youth is associated with a specific impairment of beta-cell responsiveness distinct from the deterioration of insulin sensitivity.