We aimed to investigate sex-related glycemic and cardiovascular responses after intensity- (moderate) and duration- (30 minutes) matched interval aerobic exercise (IAE) and continuous (CAE) aerobic exercise sessions in patients with type 1 diabetes mellitus (T1DM). A total of 19 volunteers (10 women) participated in 2 randomized and crossover sessions (1:1). Heart rate, systolic and diastolic blood pressure, double product, and blood glucose (BG) levels were measured before (PRE), immediately after (POST-0), and 20 minutes after (POST-20) each session. The rates of perceived exertion (RPE) and enjoyment levels (ELs) were assessed after each session. Generalized estimating equations were used to analyze the data (condition × time × sex). Regarding sex-related changes, men showed BG reductions at POST-0 and POST-20 after CAE (∆: -3.7 and -3.7 mmol/L, respectively) and only at POST-0 after IAE (∆: -1.6 mmol/L), with 1 episode of hypoglycemia occurring in the latter group. In contrast, women showed reduced BG values only after CAE at both time points (∆: -1.4 and -1.7 mmol/L) compared with PRE values. The decrease in BG levels at both time points was higher for men after CAE than IAE. Cardiovascular responses, RPEs, and ELs were similar between exercise sessions, except for blood pressure, which showed higher values in men. In conclusion, lower BG levels were observed after CAE, with greater reductions in men. Similar cardiovascular, RPE, and EL responses were found across sexes and sessions. Consideration of sex-specific recommendations may be warranted when prescribing aerobic exercise, particularly, for men with irregular physical activity levels.

The magnitude of diabetes mellitus (DM) has increased in recent decades, where the number of cases and the proportion of the disease have been gradually increasing over the past few decades. The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease. The prevalence of type 1 DM (T1DM) is increasing globally, and it has a very significant burden on countries and at an individual level. T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications. This study aims to discuss the health benefits of physical activity (PA) in T1DM patients. The present review article was performed following a comprehensive literature search. The search was conducted using the following electronic databases: "Cochrane Library", Web of Science, PubMed, HINARI, EMBASE, Google for grey literature, Scopus, African journals Online, and Google Scholar for articles published up to June 21, 2021. The present review focused on the effects of PA on many outcomes such as blood glucose (BG) control, physical fitness, endothelial function, insulin sensitivity, well-being, the body defense system, blood lipid profile, insulin resistance, cardiovascular diseases (CVDs), insulin requirements, blood pressure (BP), and mortality. It was found that many studies recommended the use of PA for the effective management of T1DM. PA is a component of comprehensive lifestyle modifications, which is a significant approach for the management of T1DM. It provides several health benefits, such as improving BG control, physical fitness, endothelial function, insulin sensitivity, well-being, and the body defense system. Besides this, it reduces the blood lipid profile, insulin resistance, CVDs, insulin requirements, BP, and mortality. Overall, PA has significant and essential protective effects against the health risks associated with T1DM. Even though PA has several health benefits for patients with T1DM, these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular. However, several effective strategies have been identified to control exercise-induced hypoglycemia in these patients. Finally, the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. It also provides suggestions for the future direction of research in this field.

This cross-sectional study aimed to investigate sex-related glycemic, cardiovascular, and enjoyment responses after intensity-(moderate) and duration-(30 min) matched aerobic (AE) and strength exercises sessions (SE) in type 1 diabetic (T1DM) patients.

Twelve volunteers performed randomly three exercise sessions: AE, strength exercises A (SEA) and B (SEB). Heart rate, systolic and diastolic blood pressure, double product (DP) and capillary blood glucose (BG) levels were measured pre (PRE), immediately (POST-0) and 20 min (POST-20) after each exercise session. Rating of perceived exertion and enjoyment level were also measured. A generalized mixed model was used to verify responses over time (p < 0.05). Effect size (ES) was also calculated.

Men shown reduced BG levels (POST-0 and POST-20), besides presenting lower values than women in both time points after AE. BG was found reduced POST-0 (SEA and SEB) and POST-20 (SEA) in men, and POST-0 and POST-20 min (SEA) in women compared to PRE (ES was moderate, large or very large), without causing hypoglycemic episodes. However, no differences between sexes were seen concerning strength sessions. Cardiovascular parameters and enjoyment levels were similar between exercise sessions.

When aerobic and strength exercise sessions are intensity- and duration-matched, lower glucose levels are seen in men after AE, but similar values are found regarding SE. These findings suggest that sex-specific recommendations may be considered when prescribing exercise for T1DM patients.

The aim of the study was to assess the effect of dietary macronutrients on circulating glucagon and insulin levels in obese and normal-weight women. Potentially, the impaired release of glucagon may proceed abnormal glucose metabolism in obese patients ahead of overt diabetes. In 20 insulin-sensitive women (11 obese and 9 normal-weight), plasma concentrations of insulin and glucagon levels were assessed before and after 3 different macronutrient test meals. AUCtotal insulin in the obese group was increased after protein and carbohydrates compared to fatty test meal consumption (3981 ± 2171 and 4869 ± 2784 vs. 2349 ± 1004 μIU∗h/m, p < 0.05, respectively), but without a difference between protein and carbohydrates ingestion. However, in the normal-weight group, AUCtotal insulin was increased after carbohydrates compared to fatty test meal ingestion (3929 ± 1719 vs. 2231 ± 509 μIU∗h/ml, p < 0.05) and similar after carbohydrate and protein as well as after fatty and protein test meals (3929 ± 1719 vs. 2231 ± 509 vs. 3046 ± 1406 μIU∗h/ml, respectively). However, AUCtotal insulin was significantly increased in obese compared to normal-weight women only after carbohydrate test meal ingestion (4869 ± 2784 vs. 3929 ± 1719 μIU∗h/ml, p < 0.05). AUCtotal glucagon was similar after carbohydrate, protein, and fatty test meals ingestion in obese and normal-weight women (921 ± 356 vs. 957 ± 368 vs. 926 ± 262 ng∗h/ml and 1196 ± 14 vs. 1360 ± 662 vs. 1792 ± 1176 ng∗h/ml, respectively). AUCtotal glucagon was significantly lower in obese than normal-weight women after a fatty meal (926 ± 262 vs. 1792 ± 1176 ng∗h/ml, p < 0.01). Postprandial glucagon secretion is not related to the macronutrient composition of the meal in normal-weight women since postprandial glucagon concentrations were stable and did not change after carbohydrate, protein, and fatty test meals. Lower glucagon secretion was observed in obese subjects after fatty meal consumption when compared to normal-weight subjects. Postprandial insulin profile was significantly higher after carbohydrate than fatty test meal intake in the obese group and did not differ between obese and normal-weight groups after carbohydrate, protein, and fatty test meals consumption. Impaired glucagon secretion after fatty meat suggests early pancreatic alpha-cell dysfunction, after a carbohydrate meal is a compensatory mechanism.

The Wilderness Medical Society convened an expert panel in 2018 to develop a set of evidence-based guidelines for the treatment of type 1 and 2 diabetes, as well as the recognition, prevention, and treatment of complications of diabetes in wilderness athletes. We present a review of the classifications, pathophysiology, and evidence-based guidelines for planning and preventive measures, as well as best practice recommendations for both routine and urgent therapeutic management of diabetes and glycemic complications. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks or burdens for each recommendation.

In adults with type 1 diabetes, resistance exercise (RE) is associated with more stable blood glucose (BG) levels than aerobic exercise, both during and after exercise. In individuals without diabetes, growth hormone and epinephrine responses to RE differ between the sexes. These hormones are known to affect BG levels in individuals with type 1 diabetes. In this study, we explored whether sex-related differences may exist in BG responses to RE in individuals with type 1 diabetes.

A secondary data analysis was conducted on pooled data from 2 studies with identical RE protocols for individuals with type 1 diabetes (13 males, age range 16 to 63 years; 10 females, age range 19 to 45 years). The RE session consisted of 7 resistance-based exercises performed at 5 pm. Plasma glucose samples were collected before, immediately after and 1 h after exercise. Interstitial glucose levels were recorded through blinded continuous glucose monitoring 24 h before, during and 24 h after exercise.

There was a significant sex-by-time interaction (p<0.001) in plasma glucose responses to RE. Plasma glucose decreased significantly in males from 8.6±2.5 to 6.3±2.1 mmol/L (p<0.001) during exercise, whereas females experienced no significant change (7.2±1.3 to 7.3±1.3 mmol/L, p=0.999). In the 6 h after RE, males developed significantly more hypoglycemia, as measured by continuous glucose monitoring (p=0.048).

Males may have a greater risk of hypoglycemia with an acute bout of RE than females. Further research is needed to examine this phenomenon more closely, as sex-specific recommendations for preventing hypoglycemia around RE may be necessary in type 1 diabetes.

Sex-related differences in metabolic and neuroendocrine response to exercise in individuals without diabetes have been well established. Men and women differ in fuel selection during exercise, in which women rely to a greater extent on fat oxidation, whereas males rely mostly on carbohydrate oxidation for energy production. The difference in fuel selection appears to be mediated by sex-related differences in hormonal (including catecholamines, growth hormone, and estrogen) response to different types and intensities of exercise. In general, men exhibit an amplified counter-regulatory response to exercise, with elevated levels of catecholamines compared with women. However, women exhibit greater sensitivity to the lipolytic action of the catecholamines and deplete less of their glycogen stores than men during exercise, which suggests that women may experience a greater defense in blood glucose control after exercise than men. Conversely, little is known about sex-related differences in response to exercise in individuals with type 1 diabetes (T1D). A single study investigating sex-related differences in response to moderate aerobic exercise in individuals with T1D found sex-related differences in catecholamine response and fuel selection, but changes in blood glucose were not measured. To our knowledge, there are no studies investigating sex-related differences in blood glucose responses to different types and intensities of exercise in individuals with T1D. This review summarizes sex-related differences in exercise responses that could potentially impact blood glucose levels during exercise in individuals with T1D and highlights the need for further research.

Closed-loop systems for patients with type 1 diabetes are progressing rapidly. Despite these advances, current systems may struggle in dealing with the acute stress of exercise. Algorithms to predict exercise-induced blood glucose changes in current systems are mostly derived from data involving relatively young, fit males. Little is known about the magnitude of confounding variables such as sex, age, and fitness level-underlying, uncontrollable factors that might influence blood glucose control during exercise. Sex-related differences in hormonal responses to physical exercise exist in studies involving individuals without diabetes, and result in altered fuel metabolism during exercise. Increasing age is associated with attenuated catecholamine responses and lower carbohydrate oxidation during activity. Furthermore, higher fitness levels can alter hormonal and fuel selection responses to exercise. Compounding the limited research on these factors in the metabolic response to exercise in type 1 diabetes is a limited understanding of how these variables affect blood glucose levels during different types, timing and intensities of activity in individuals with type 1 diabetes (T1D). Thus, there is currently insufficient information to model a closed-loop system that can predict them accurately and consistently prevent hypoglycemia. Further, studies involving both sexes, along with a range of ages and fitness levels, are needed to create a closed-loop system that will be more precise in regulating blood glucose during exercise in a wide variety of individuals with T1D.

Physical activity (PA) can improve cardiovascular risk in the general population and in patients with type 2 diabetes. Studies also indicate an HbA(1c)-lowering effect in patients with type 2 diabetes. Since reports in patients with type 1 diabetes are scarce, this analysis aimed to investigate whether there is an association between PA and glycemic control or cardiovascular risk in subjects with type 1 diabetes.

A total of 18,028 adults (≥18 to <80 years of age) from Germany and Austria with type 1 diabetes from the Diabetes-Patienten-Verlaufsdokumentation (DPV) database were included. Patients were stratified according to their self-reported frequency of PA (PA0, inactive; PA1, one to two times per week; PA2, more than two times per week). Multivariable regression models were applied for glycemic control, diabetes-related comorbidities, and cardiovascular risk factors. Data were adjusted for sex, age, and diabetes duration. P values for trend were given. SAS 9.4 was used for statistical analysis.

An inverse association between PA and HbA(1c), diabetic ketoacidosis, BMI, dyslipidemia (all P < 0.0001), and hypertension (P = 0.0150), as well as between PA and retinopathy or microalbuminuria (both P < 0.0001), was present. Severe hypoglycemia (assistance required) did not differ in PA groups (P = 0.8989), whereas severe hypoglycemia with coma was inversely associated with PA (P < 0.0001).

PA seemed to be beneficial with respect to glycemic control, diabetes-related comorbidities, and cardiovascular risk factors without an increase of adverse events. Hence, our data underscore the recommendation for subjects with type 1 diabetes to perform regular PA.

The primary focus of this review is threefold: first, to summarize available knowledge on exercise-associated glucose metabolism in individuals with type 1 diabetes mellitus (T1DM); second, to elucidate physiological mechanisms predisposing to glycemic variations in patients in T1DM; and third, to describe novel approaches derived from physiological perceptions applicable to stabilize exercise-related glycemia in individuals with T1DM.

Recent studies corroborate the concept that despite partial differences in counter-regulatory mechanisms individuals with T1DM do not fundamentally differ in their glucose response to exercise when compared with healthy individuals if studies are performed under standardized conditions with insulin and glucose levels held close to physiological ranges. Novel approaches derived from a better understanding of exercise-associated glucose metabolism (e.g., the concept of intermittent high-intensity exercise) may provide alternative ways to master the challenges imposed by exercise to individuals with T1DM.

Exercise still imposes high demands on patients with T1DM and increases risks for hypoglycemia and hyperglycemia. Deeper insight into the associated metabolic pathways has revealed novel options to stabilize exercise-associated glucose levels in these patients.

To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of (1)H NMR-spectrometry.

The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler.

The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle.

The (1)H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.

Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver.

Physical activity is a critical component in the care of diabetes. Although it offers health benefits it presents challenges.

To investigate differences between adolescent boys and girls with type 1 diabetes and healthy controls in terms of maximal work capacity (VO(2) max) and hormonal response to physical exercise of different intensities.

Twelve individuals (six boys and six girls; age 14-19 yr, pubertal stage 4-5) with type 1 diabetes (duration, 6.3 ± 4.4 yr; hemoglobin A1c, 63 ± 10 mmol/mol) were compared with 12 healthy controls matched for age, sex, pubertal stage, body mass index standard deviation score, and amount of regular physical activity.

During consecutive days, three different workloads; maximal, endurance, and interval, were performed on an Ergometer cycle. During the tests, levels of lactate, glucose, insulin, and regulatory hormones [glucagon, cortisol, growth hormone (GH), adrenaline, and noradrenaline] were measured in blood. Subcutaneous glucose was measured continuously.

VO(2) max did not differ between the groups, diabetes 49.8 ± 9.9 vs. control 50.7 ± 12.0 mL/min/kg. Hormonal responses did not differ between the groups except for mean peak GH level during the interval test, diabetes 63.2 ± 27.0 vs. control 33.8 ± 20.9 mU/L, p < 0.05.

Physical capacity and hormonal regulation of blood glucose in connection with physical exercise of different intensities did not differ between adolescents with diabetes and healthy controls. Thus, adolescents with type 1 diabetes can participate in physical activity on the same terms as healthy peers.

Obesity, lipid disorders, type 2 diabetes, high blood pressure and coronary heart disease are frequently encountered in wealthy populations. All these disorders frequently occur as clusters, constituting the metabolic syndrome. It is currently admitted that insulin resistance plays a central role in the pathogenesis of this syndrome. Stress responses include activation of the sympathetic nervous system and stimulation of epinephrine and cortisol release. These hormones may over the long term reduce insulin sensitivity. Cortisol may also favour the development of central obesity. In healthy individuals, mental stress increases heart rate, but simultaneously decreases vascular resistance in skeletal muscle. This results in a moderate increase in blood pressure, and an acute increase in insulin-mediated glucose disposal. In obese patients, mental stress elicits responses which differ widely from those of healthy individuals. While mental stress enhances catecholamine-mediated energy expenditure in obese patients to the same extent as in lean subjects, it fails to decrease systemic vascular resistance due to endothelial dysfunction. This leads to enhanced blood pressure responses and the absence of stimulation of glucose disposal in obese subjects during mental stress. It can be hypothesized that repeated professional or social stress may activate the sympathoadrenal system, resulting in high cortisol levels, stimulation of the sympathetic nervous system, and epinephrine secretion. All these factors may eventually lead to the development of central obesity and insulin resistance. Furthermore, the blood pressure responses to mental stress may be enhanced in insulin-resistant individuals, favouring the development of vascular complications.

In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.

Recently, incretin-related therapy has been developed for the new treatment of diabetes mellitus; however, incretin response to glucose ingestion in normal glucose tolerant (NGT) subjects has not been clarified in detail with special reference to the role of incretin hormones, glucagon, and a family history of diabetes.

We conducted a 75 g oral glucose tolerance test in 30 NGT subjects.

The total glucose-dependent insulinotropic peptide (GIP)-AUC(0-120) (area under the curve over a period of 0-120 minutes) was correlated with immunoreactive insulin (IRI)-AUC(0-120) (P<0.05), insulinogenic index (II; P<0.05), ΔIRI between 0 and 120 minutes (P<0.05). Active glucagon-like peptide-1 (GLP-1) AUC(0-120) was correlated inversely both with Δ glucose between 0 and 30 minutes (P<0.01) and with Δ immunoreactive glucagon between 0 and 30 minutes (P<0.05). Δ Total GIP between 0 and 15 minutes (P<0.01), Δ total GIP between 0 and 30 minutes (P<0.05), and the total GIP-AUC(0-120) (P<0.05) in the subjects with a family history of type 2 diabetes were significantly higher than those in the subjects without a family history.

These results suggest that GIP possibly facilitates insulin secretion in response to oral glucose load directly and active GLP-1 may exert the glucoregulatory action via the suppression of glucagon secretion in NGT subjects. Notably, the subjects with a family history of diabetes exert significantly higher GIP response in the early phase of glucose load compared with those without a family history.

Pediatric obesity, a major risk factor for cardiovascular diseases and diabetes, has steadily increased in the last decades. Although excessive inflammation and oxidation are possible biochemical links between obesity and cardiovascular events in adults, little information is available in children. Furthermore, effects of gender and fitness on the interaction between dyslipidemia and oxidative/inflammatory stress in children are mostly unknown.

Therefore, we measured systemic markers of oxidation (F(2)-isoprostanes [F(2)-IsoP] and antioxidants) and inflammation (interleukin-6 [IL-6] and leukocyte counts) and metabolic variables in 113 peripubertal children (55 obese [Ob] age and gender-adjusted BMI% ≥ 95(th), 25 Females [F]; 15 overweight [OW] BMI% 85(th)-95(th), 8 F; 43 normoweight [NW] 25 F).

When compared with NW, Ob displayed elevated F(2)-IsoP (99 ± 7 vs. 75 ± 4 pg/mL, p<0.005), IL-6 (2.2 ± 0.2 vs. 1.5 ± 0.3 pg/mL, p<0.005), elevated total leukocytes and neutrophils, altered levels of total cholesterol , low- and high-density-lipoprotein cholesterol, triglycerides, free fatty acids, glucose, and insulin (all p<0.005). This pattern was present in both genders and over a broad range of fitness in Ob.

Our data indicate that alterations in metabolic control and a concomitant increase in inflammation and oxidative stress occur early in life in obese children, likely exposing both genders to a similar degree of increased risk of future cardiovascular diseases.

Current recommendations are that people with Type 1 and Type 2 diabetes mellitus exercise regularly. However, in cases in which insulin or insulin secretagogues are used to manage diabetes, patients have an increased risk of developing hypoglycemia, which is amplified during and after exercise. Repeated episodes of hypoglycemia blunt autonomic nervous system, neuroendocrine and metabolic defenses (counter-regulatory responses) against subsequent episodes of falling blood glucose levels during exercise. Likewise, antecedent exercise blunts counter-regulatory responses to subsequent hypoglycemia. This can lead to a vicious cycle, by which each episode of either exercise or hypoglycemia further blunts counter-regulatory responses. Although contemporary insulin therapies cannot fully mimic physiologic changes in insulin secretion, people with diabetes have several management options to avoid hypoglycemia during and after exercise, including regularly monitoring blood glucose, reducing basal and/or bolus insulin, and consuming supplemental carbohydrates.

Exercise is a cornerstone of diabetes therapy in type 1 diabetes mellitus (DMT1) patients. The type of exercise is important in determining the propensity to hypoglycemia. We assessed, by continuous glucose monitoring (CGM), the glucose profiles during and in the following 20h after a session of two different types of exercise.

Eight male volunteers with well-controlled DMT1 were studied. They underwent 30min of both intermittent high-intensity exercise (IHE) and moderate-intensity exercise (MOD) in random order. Expired air was recorded during exercise, while metabolic and hormonal determinations were performed before and for 120 min after exercises. The CGM system and activity monitor were applied for the subsequent 20h.

Blood glucose level declined during both type of exercise. At 150 min following the start of exercise, plasma glucose content was slightly higher after IHE. No changes were observed in plasma insulin concentration. A significant increase of norepinephrine concentration was noticed during IHE. Between midnight and 6:00 a.m. the glucose levels were significantly lower after IHE than those observed after MOD (area under the curve, 23.3 ± 3 vs. 16 ± 3 mg/dL/420 min [P = 0.04]; mean glycemia at 3 a.m., 225 ± 31 vs. 147 ± 17 mg/dL [P<0.05]). The number of hypoglycemic episodes after IHE was higher than that observed after MOD (seven vs. two [P<0.05]).

We demonstrate that (1) CGM is a useful approach in DMT1 patients who undergo an exercise program and (2) IHE is associated with delayed nocturnal hypoglycemia.

Previously, we showed that our post-natal handling model induces pro-opiomelanocortin-derived (POMC) endogenous systems alterations in male mice at weaning. These alterations last up to adult age, and are at the basis of adult hormonal and metabolic conditions similar to mild metabolic syndrome/type-2 diabetes. Here, we evaluate how sex influences post-natal programming in these metabolic conditions. Subjects are adult control (non-handled) female (NHF) and male (NHM) CD-1 mice; adult post-natal handled female (HF) and male (HM) mice. Handling consists of daily maternal separation (10 min) plus sham injection, from birth to weaning (21 days). In adult handled males (90-days old) we find not only POMC-derived hormones alterations (enhanced basal plasma corticosterone (+91%) and ACTH (+109%)) but also overweight (+5.4%), fasting hyperglycemia (+40%), hypertriglyceridemia (+21%), enhanced brain mRNA expression of hydroxysteroid(11-beta)dehydrogenase type-1 (HSD11B1) (+49%), and decreased mRNA-HSD11B2 (-39%). Conversely, uric acid, creatinine, HDL(C), total cholesterol, glucose and insulin incremental area under-the-curve are not affected. In females, post-natal handling does not produce both hormonal and dysmetabolic diabetes-like changes; but handling enhances n3- and n6-poly-unsaturated, and decreases saturated fatty acids content in erythrocyte membrane composition in HF versus NHF. In conclusion, for the first time we show that female sex in mice exerts effective protection against the hypothalamus-pituitary-adrenal homeostasis disruption induced by our post-natal handling model on POMC cleavage products; endocrine disruption is in turn responsible for altered metabolic programming in male mice. The role of sex hormones is still to be elucidated.

To compare exercise-induced growth hormone (GH) response in patients with Type 1 diabetes during stable euglycaemic and hyperglycaemic conditions.

We conducted a randomized, controlled, single-blinded cross-over trial in seven male patients with well-controlled Type 1 diabetes. The patients cycled twice for 120 min at a level of 55-60% maximal oxygen uptake. Euglycaemia was at 5.0 mmol/l, hyperglycaemia at 11.0 mmol/l.

Area under the curve of GH (AUC(GH)) during exercise was significantly higher during euglycaemia [1430 ng ml(-1) min, 95% confidence interval (CI) 703-2910] compared with hyperglycaemia (1061 ng ml(-1) min, 95% CI 538-2091, P = 0.02).

In patients with Type 1 diabetes, GH concentrations during moderate aerobic exercise during stable hyperglycaemic conditions are significantly lower compared with euglycaemia. These findings are compatible with preserved glucose-mediated GH regulation during exercise in individuals with well-controlled Type 1 diabetes.

Few papers focus on exercise-related blood glucose (BG) in patients on continuous sc insulin infusion (CSII) or multiple daily injections (MDI) with glargine.

The main objective was to evaluate the degree of glycemic control in Type 1 diabetes mellitus adolescents on CSII doing physical activity with pump switched on or off. These findings were also compared with a small group of patients on MDI with glargine.

Eight patients on CSII (basal rate continued or turned off in alternating sessions) and 5 on MDI joined 4 sessions of moderate-severe exercise.

Post-exercise BG significantly increased with the pump off and was unchanged/decreased with the pump on and MDI groups vs baseline. The hypoglycemia rate was not different among the 3 groups at any time. Pump on: hypoglycemias more frequent both at bedtime (p=0.031) and at awakening (p<0.001) than before dinner and at awakening than at bed-time (p=0.044). Pump off: hypoglycemias more frequent both at bed-time (p=0.010) and at awakening (p=0.031) than before dinner. MDI: no differences.

Glargine is safe and reducing the pre-lunch insulin is unnecessary. Subjects on insulin pump should not stop the basal rate. If they stop the pump, some actions are advisable: pre-exercise insulin bolus, pre-sleeping snack rich in carbohydrates, slight reduction of the overnight basal rate. On the other hand, if the basal rate is unmodified, the ingestion of sugary drinks during the exercise, the reduction of the overnight basal rate, a reduction of the pre-dinner insulin bolus and/or a pre-sleeping snack should be considered.

Influences of gender and body weight on the hormonal response to eating are not well understood. This study was conducted to determine a convenient time-point to evaluate peak postprandial hormone responses and to test the hypothesis that gender and BMI interact to produce differences in postprandial secretion of selected humoral markers implicated in hunger and satiety.

Fasting blood glucose, insulin, leptin, ghrelin, glucagon-like peptide-1, and glucagon were measured in normal-weight (20 <or= BMI < 25 kg/m2) men (n = 10) and women (n = 9) and obese (BMI >or= 30 kg/m2) men (n = 9) and women (n = 11). A standard liquid meal was consumed, and humoral measurements were repeated every 10 minutes for 1 hour. Data were analyzed using repeated measures ANOVA with BMI and gender as main effects.

Obese subjects had delayed peak insulin responses (p = 0.004), whereas obese men had a delayed nadir ghrelin response (p = 0.05). Obese subjects had higher and more sustained postprandial glucose (p = 0.02), and greater fasting (p = 0.0004) and postprandial insulin (p = 0.0001). Ghrelin decreased after the meal (p = 0.003); the percent change from fasting tended to be reduced in obese subjects (p = 0.07). Men had greater fasting (p = 0.02) and postprandial (p = 0.03) glucagon and a subtle postprandial decline in plasma leptin (p = 0.01).

Peak hormone responses occurred 20 to 40 minutes after eating. Measurements made during this interval may be useful in evaluating postprandial response magnitude. Peak/nadir responses and time courses of postprandial responses are influenced by gender and BMI. Nutritional studies need to account for variability introduced by these factors.

The Diabetes Control and Complications Trial demonstrated that tight control of diabetes management greatly reduces the risk of microvascular complications of diabetes. Unfortunately, tight control of blood glucose can also result in hypoglycemia, especially in patients with type 1 diabetes mellitus (T1DM). It is now widely recognized that antecedent hypoglycemia can blunt neuroendocrine, autonomic nervous system (ANS), and metabolic counterregulatory responses to subsequent hypoglycemia. Thus, blunted counterregulatory defenses against falling plasma glucose levels are a major risk factor for hypoglycemia in people with diabetes. This risk is also complicated by a difference in responses between males and females. Because of the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we developed studies to determine whether neuroendocrine and ANS counterregulatory dysfunction play a role in the pathogenesis of exercise-related hypoglycemia in T1DM. Results from these studies have shown that neuroendocrine (catecholamine and glucagon), ANS (muscle sympathetic nerve activity), and metabolic (lipolysis and glucose kinetics) responses are blunted during exercise after antecedent hypoglycemia, and that there is a sexual dimorphism in responses. Similarly, antecedent episodes of exercise can blunt counterregulatory responses during subsequent hypoglycemia, thereby creating reciprocal feed-forward vicious cycles that increase the risk of hypoglycemia during either stress.

Circumstantial evidence suggests that an increase in plasma glucose availability improves exercise capacity in subjects with type 1 diabetes mellitus. The aim of this study was to assess exercise capacity in eu- and hyperglycaemic conditions in subjects with type 1 diabetes.

Eight moderately exercise-trained male subjects with type 1 diabetes on continuous subcutaneous insulin infusion were studied. Using identical insulin infusion rates, the patients were randomly allocated to perform two stepwise ergometer tests in eu- and hyperglycaemic clamp conditions. The primary endpoint was the peak power output; the secondary endpoints comprised the rate of perceived exertion, lactate levels, heart rate, and respiratory exchange ratio.

Eu- and hyperglycaemic clamp conditions were observed at a plasma glucose concentration of 5.3 +/- 0.6 mmol/L and 12.4 +/- 2.1 mmol/L, respectively (mean +/- SD), and remained stable throughout the physical exercise. Insulin levels were similar in both conditions. Hyperglycaemia did not result in a significant increase in the peak power output compared to euglycaemia (mean paired difference of 4.96 W, 95% CI - 11.3 to 21.2, p = 0.49). Hyperglycaemia did not have a significant impact on the secondary endpoints compared to euglycaemia. Sensitivity analyses confirmed these results.

In subjects with type 1 diabetes, exercise capacity is not influenced by hyperglycaemia. Comparable levels of lactate and similar respiratory exchange ratio suggest that an increase in extracellular glucose availability did not translate into increased intracellular glucose oxidation.

Exercise-induced growth hormone (GH) secretion may significantly modulate growth and development in children. Altered physiological GH responses, therefore, may reduce the beneficial effects of exercise. High-fat food ingestion before exercise blunts the GH response in adults, but it is unknown whether this occurs in children. We therefore performed standard exercise tests, following a high-fat meal or placebo, in 12 children, age 11-15 (6 M, 6 F). GH, insulin-like growth factor-I, glucose, insulin, glucagon, cortisol, epinephrine and interleukin-6 samples were drawn at baseline, end-exercise, and 30 and 60 min post-exercise. While GH was similar at baseline in all experiments, the exercise-induced GH peak was lower after the high-fat meal (6.7 +/- 1.6 ng/l vs 11.8 +/- 2.4 ng/l, p <0.02). Other exercise responses were not affected by prior fat ingestion. A high-fat meal before exercise, therefore (a common event in Western societies), may reduce the growth factor response to exercise in children, with potential implications for growth and development.

In children with type 1 diabetes (T1DM), altered adaptive responses to exercise (secretion of growth factors, inflammatory cytokines, and glucoregulatory mediators) may have potential implications in growth and development, early onset of disease complications, and incidence of hypoglycemia. We therefore measured a broad spectrum of exercise responses in 12 children with T1DM (seven males and five females) and 12 controls (six males / six females) aged 11-15 yr, during a 30-min exercise challenge @ 80% VO(2)max. Euglycemia was strictly controlled during exercise, and in diabetic patients a basal rate of i.v. insulin was allowed to maintain baseline insulin concentrations. Throughout the experiment, interleukin-6 (IL-6) concentrations (pg/mL) were markedly higher in T1DM vs. controls (preexercise: 5.0+/-1.3 vs. 1.9+/-0.6, p<0.02; end-exercise 5.3+/-1.2 vs. 2.7+/-1.0, p<0.05; 30-min postexercise: 8.2+/-2.2 vs. 3.9+/-0.8, p<0.05). A similar pattern was also observed with norepinephrine. Growth hormone (GH) concentration was similar in both groups at baseline and end-exercise, but in T1DM the exercise-induced GH remained significantly elevated 30 min after exercise (9.2+/-2.2 vs. 3.1+/-0.9 ng/L, p<0.01). The exercise-induced increase in glucagon elicited by exercise in controls was similar to that previously observed in healthy adults (10+/-3 pg/mL); however, it was significantly blunted in T1DM children (2+/-2 pg/mL, p<0.05). In conclusion, T1DM children displayed significant alterations in multiple aspects of their adaptive response to intense exercise.

The present study describes the cardiovascular responses to epinephrine (Epi) given into the arm, in adult patients with acute allergic reactions, and the differential responses to subcutaneous (SC) and intramuscular (IM) administration. Sixty-three adult patients were treated with Epi administered SC or IM after H1 and H2 receptor blockade. Heart rate and blood pressure (BP) were then measured for 20 minutes. Changes in heart rate and BP variables were analyzed. Pulse pressure and systolic BP showed increases with time. Diastolic BP also showed a modestly decreasing values over time. Heart rates did not change. Time-related changes between IM and SC Epi treatment were not observed. Sex influenced timed BP values and a significant sex by time effect was observed. In subset analysis, only male patients showed an overall time effect for BP variables, especially pulse pressure. In conclusion, adults with acute allergic syndromes treated with arm-injected Epi show a modest but definite increase in pulse pressure and systolic BP. This pattern is observed more in males. Heart rate and blood pressure differences between IM and SC arm-injected Epi treatments do not appear to be significant.

The effects of type 1 diabetes on the contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production (GP) at rest and during moderate (MOD) and high (HI) intensity running were examined in healthy control (n = 6) and type 1 diabetic (n = 5) subjects matched for age, weight, and maximum aerobic capacity by combined noninvasive measurements of hepatic glycogen content using (13)C nuclear magnetic resonance spectroscopy and determination of GP using [6,6-(2)H(2)]glucose. In the control subjects, GP increased in proportion to the intensity of the exercise [at rest (REST), 14.3 +/- 0.5; MOD, 18.1 +/- 0.9; HI, 28.8 +/- 1.3 micromol/(kg-min); P = 0.001, three-way comparison], and this was accounted for by an increase in the percent contribution of net hepatic glycogenolysis to GP (REST, 32 +/- 1%; MOD, 49 +/- 5%; HI, 57 +/- 5%; P = 0.006). In the diabetic subjects, resting rates of GP were 60% higher than those in the control subjects (P < 0.0001) and increased in proportion to the workload. In contrast, the contributions of net hepatic glycogenolysis to GP were consistently lower than those in the control subjects (REST, 20 +/- 6%; MOD, 32 +/- 13%; HI, 32 +/- 3%; P = 0.006 vs. control), and the exaggerated rates of GP could be entirely accounted for by increased rates of gluconeogenesis. In conclusion, 1) increases in GP in healthy control subjects with exercise intensity can be entirely attributed to increases in net hepatic glycogenolysis. 2) In contrast, moderately controlled type 1 diabetic subjects exhibit increased rates of GP both at rest and during exercise, which can be entirely accounted for by increased gluconeogenesis.

Various threatening stimuli, such as pain, low blood pressure, or infection, elicit a set of neuroendocrine responses that include an increased secretion of catecholamines and glucocorticoid from the adrenal gland and activation of the sympathetic nervous system. These hormonal secretions allow a "fight or flight" response by mobilizing endogenous substrate. They also exert anti-insulin actions, and may in the long term induce a state of insulin resistance. In addition, stress stimulates inflammatory mediators in mononuclear cells. Given the possible role of low-grade inflammation in chronic metabolic disorders, this suggests that stress may be a factor in the development of insulin resistance and the metabolic syndrome.

Studies reviewed in this article cover: (1) the metabolic and haemodynamic effects of stress in healthy and insulin-resistant individuals; (2) the relationship between stress and inflammation and the role of the autonomic nervous system; and (3) some factors known to modulate the neuroendocrine responses to stress. Future perspectives, together with some hints regarding the role of neurotrophins such as brain-derived neurotrophic factor, are delineated.

Recent work performed in the field has indicated that stress may be a significant factor in the pathogenesis of metabolic disorders. Nutritional intervention or pharmacological agents targeted at modulating stress should be investigated.