Regular physical activity (PA) for youth with diabetes improves cardiorespiratory fitness, body composition, bone health, insulin sensitivity, and psychosocial well-being. However many youth with diabetes or pre-diabetes fail to meet minimum PA guidelines and a large percentage of youth with diabetes are overweight or obese. Active youth with type 1 diabetes tend to have lower HbA1c levels and reduced insulin needs, whereas activity in adolescents at-risk for type 2 diabetes improves various measures of metabolism and body composition. Insulin and nutrient adjustments for exercise in type 1 diabetes is complex because of varied responses to exercise type and because of the different times of day that exercise is performed. This review highlights the benefits of exercise and the established barriers to exercise participation in the pediatric diabetes population. A new exercise management algorithm for insulin and carbohydrate intake strategies for active youth with type 1 diabetes is presented.

Second-generation antipsychotics (SGAs) are increasingly used for a variety of mental illnesses; however, the data regarding the safety of these medications during pregnancy are inconclusive and contradictory. We examined the risk of adverse pregnancy outcomes associated with in utero exposure to SGAs by conducting a systematic review and meta-analysis. We searched the databases EMBASE and MEDLINE from January 1990 to December 2014. Eligible studies had to report pregnant women who took SGAs during pregnancy (first trimester exposure if analyzing congenital malformations), follow a healthy comparison group in a similar manner, and report data on pregnancy outcomes. There was no restriction on language, sample size, or publication date. The primary outcome analyzed was major congenital malformations, and secondary outcomes included miscarriages, stillbirths, preterm births, small or large for gestational age neonates, and differences in gestational ages and birth weights. A total of 12 studies met our inclusion criteria, totalling 1782 cases and 1,322,749 controls. The use of SGA during the first trimester of pregnancy was associated with a significant increased risk for major congenital malformations (odds ratio, 2.03; 95% confidence interval, 1.41-2.93); however, no specific pattern of malformations was found. An increased risk was also found for preterm births (odds ratio, 1.85; 95% CI, 1.20-2.86). The use of SGA during pregnancy was not found to be associated with an increased risk for secondary outcomes analyzed. The absence of a specific pattern of malformations makes it difficult to identify an explicit risk posed by SGAs, and therefore, further studies sufficiently controlling for confounding factors are needed to validate these findings.

Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. This phenomenon has been attributed, in part, to the actions of stress hormones as well as local and systemic inflammation. We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wk old) underwent a "training" protocol of 24-h voluntary running wheel access and CR (15-20 g/day; ~50-65% of ad libitum intake) for 3 wk ("All Trained") or were sedentary and fed ad libitum ("Sed"). After 3 wk, All Trained were randomly divided into one group which was terminated immediately ("Trained"), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked groups received either a daily gavage of a placebo ("Detrained + Placebo") or curcumin (200 mg/kg) ("Detrained + Curcumin"). Cessation of daily CR and exercise caused an increase in body mass, as well as a 9- to 14-fold increase in epididymal, perirenal, and inguinal adipose tissue mass, all of which were attenuated by curcumin ( P < 0.05). Insulin area under the curve (AUC) during an oral glucose tolerance test, HOMA-IR, and C-reactive protein (CRP) were elevated 6-, 9-, and 2-fold, respectively, in the Detrained + Placebo group vs. the Trained group (all P < 0.05). Curcumin reduced insulin AUC, HOMA-IR, and CRP vs. the placebo group (all P < 0.05). Our results indicate that curcumin has a protective effect against weight regain and impaired metabolic control following a successful period of weight loss through diet and exercise, perhaps via inhibition of glucocorticoid action and inflammation. NEW & NOTEWORTHY Weight regain after dieting and exercise is a common phenomenon plaguing many individuals. The biological mechanisms underlying weight regain are incompletely understood and are likely multifactorial. In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise.

Teich T, Dunford EC, Porras DP, Pivovarov JA, Beaudry JL, Hunt H, Belanoff JK, Riddell MC. Glucocorticoid antagonism limits adiposity rebound and glucose intolerance in young male rats following the cessation of daily exercise and caloric restriction. Am J Physiol Endocrinol Metab 311: E56 -E68, 2016. First published May 3, 2016 doi:10.1152/ajpendo.00490.2015.-Severe caloric restriction (CR), in a setting of regular physical exercise, may be a stress that sets the stage for adiposity rebound and insulin resistance when the food restriction and exercise stop. In this study, we examined the effect of mifepristone, a glucocorticoid (GC) receptor antagonist, on limiting adipose tissue mass gain and preserving whole body insulin sensitivity following the cessation of daily running and CR. We calorically restricted male Sprague-Dawley rats and provided access to voluntary running wheels for 3 wk followed by locking of the wheels and reintroduction to ad libitum feeding with or without mifepristone (80 mg·kg Ϫ1 ·day Ϫ1 ) for 1 wk. Cessation of daily running and CR increased HOMA-IR and visceral adipose mass as well as glucose and insulin area under the curve during an oral glucose tolerance test vs. pre-wheel lock exercised rats and sedentary rats (all P Ͻ 0.05). Insulin sensitivity and glucose tolerance were preserved and adipose tissue mass gain was attenuated by daily mifepristone treatment during the post-wheel lock period. These findings suggest that following regular exercise and CR there are GC-induced mechanisms that promote adipose tissue mass gain and impaired metabolic control in healthy organisms and that this phenomenon can be inhibited by the GC receptor antagonist mifepristone. exercise; caloric restriction; glucocorticoid antagonism; glucose intolerance; adiposity rebound REPEATED BOUTS OF WEIGHT LOSS and weight regain, termed weight cycling, have been associated with a greater risk for developing cardiovascular disease and type 2 diabetes over time (5,20,26). Although caloric restriction (CR) and regular exercise reduce body fat content and improve metabolic health (74), a key component to their success is adherence. Following weight loss from CR in overweight or obese individuals, nearly one-half of the weight is regained within one year (16). This weight regain is associated with a marked deterioration in whole body insulin sensitivity, which may occur via increased adipose tissue hypertrophy and hyperplasia, changes in neuroendocrine inputs to adipose tissue (43), and reductions in skeletal muscle insulin sensitivity (32). Although regular exercise attenuates the metabolic drive to regain weight after long-term weight loss in animal models (44), humans tend to relapse toward more sedentary behavior after lifestyle interventions (79). Humans (1, 25, 31, 52, 57, 73) and rodents (13, 32-34, 36, 37) rapidly develop significant insulin resistance, glucose intolerance, and visceral fat growth when increased physical activity or dieting stops. Additionally, the reintroduction to ad libitum feeding followi...

A rapid deterioration of whole‐body insulin sensitivity and visceral fat mass rebound occurs following cessation of regular exercise in humans and rodents. Both dieting and daily exercise have been shown to increase intracellular visceral fat exposure to glucocorticoids (GCs) via up‐regulation of the pre‐receptor enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), a phenomenon that may predispose animals to rapid fat rebound. We hypothesized that sustained elevations of GC exposure in visceral fat, upon removal of regular exercise and caloric restriction (CR), may influence this detrimental metabolic response. Thus, we tested the efficacy of Mifepristone, a potent but non‐selective GC receptor antagonist, on limiting adiposity rebound and preserving whole‐body insulin sensitivity following cessation of daily exercise and CR. Using young male Sprague‐Dawley rats, we provided 20g/day of standard rodent chow and access to voluntary running wheels for 3 weeks followed by locking of the wheels and reintroduction to ad libitum feeding either with or without Mifepristone (80 mg/kg/day) via oral gavage for 1 week. Additional Sedentary and Control Runner groups, who were also calorie restricted (20 g/day), were used as pre‐wheel lock comparisons (n= 8‐10 per group). Cessation of daily running and CR resulted in a 6.5‐fold increase in HOMA‐IR and a 2‐fold increase in glucose AUC during an oral glucose tolerance test in Placebo vs. Control Runners (p<0.05). Mifepristone treatment abolished both of these impairments. Mifepristone also attenuated visceral fat mass rebound in epididymal depots by 14% vs. Placebo and significantly reduced perirenal fat mass rebound by 55% vs. Placebo (p<0.05). Control Runners demonstrated a 5‐fold increase in 11β‐HSD1 protein content in epididymal fat vs. Sedentary and a similar increase remained in the Placebo group one week following cessation of exercise and CR vs. Sedentary (p<0.05). Daily Mifepristone significantly reduced 11β‐HSD1 vs. Control Runners and Placebo groups (p<0.05). These findings suggest that elevations in GC action following regular exercise and dieting promote rapid deterioration in metabolic control in healthy organisms and that this deterioration can be inhibited by a GC receptor antagonist. Grant Funding Source: Supported by NSERC and Corcept Therapeutics