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Concept: Impaired fasting glycaemia

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BACKGROUND: Epidemiological studies suggest that excessive sitting time is associated with increased health risk, independent of the performance of exercise. We hypothesized that a daily bout of exercise cannot compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen healthy subjects, age 21±2 year, BMI 22.6±2.6 kgm(-2) followed randomly three physical activity regimes for four days. Participants were instructed to sit 14 hr/day (sitting regime); to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr (exercise regime); to substitute 6 hrs sitting with 4 hr walking and 2 hr standing (minimal intensity physical activity (PA) regime). The sitting and exercise regime had comparable numbers of sitting hours; the exercise and minimal intensity PA regime had the same daily energy expenditure. PA was assessed continuously by an activity monitor (ActivPAL) and a diary. Measurements of insulin sensitivity (oral glucose tolerance test, OGTT) and plasma lipids were performed in the fasting state, the morning after the 4 days of each regime. In the sitting regime, daily energy expenditure was about 500 kcal lower than in both other regimes. Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml, respectively. Triglycerides, non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise. CONCLUSIONS: One hour of daily physical exercise cannot compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting. Reducing inactivity by increasing the time spent walking/standing is more effective than one hour of physical exercise, when energy expenditure is kept constant.

Concepts: Insulin, Diabetes mellitus, Obesity, Overweight, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Impaired glucose tolerance

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Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism.

Concepts: Nutrition, Glucose, Randomized controlled trial, Glucose tolerance test, Impaired fasting glycaemia, Fat, Impaired glucose tolerance, Carbohydrate

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Objective To determine, among children with normal birth weight, if maternal hyperglycemia and weight gain independently increase childhood obesity risk in a very large diverse population. Methods Study population was 24,141 individuals (mothers and their normal birth weight offspring, born 1995-2003) among a diverse population with universal GDM screening [50-g glucose-challenge test (GCT); 3 h. 100 g oral glucose tolerance test (OGTT) if GCT+]. Among the 13,037 full-term offspring with normal birth weight (2500-4000 g), annual measured height/weight was ascertained between ages 2 and 10 years to calculate gender-specific BMI-for-age percentiles using USA norms (1960-1995 standard). Results Among children who began life with normal birth weight, we found a significant trend for developing both childhood overweight (>85 %ile) and obesity (>95 %ile) during the first decade of life with both maternal hyperglycemia (normal GCT, GCT+ but no GDM, GDM) and excessive gestational weight gain [>40 pounds (18.1 kg)]; p < 0.0001 for both trends. These maternal glucose and/or weight gain effects to imprint for childhood obesity in the first decade remained after adjustment for potential confounders including maternal age, parity, as well as pre-pregnancy BMI. The attributable risk (%) for childhood obesity was 28.5 % (95 % CI 15.9-41.1) for GDM and 16.4 % (95 % CI 9.4-23.2) for excessive gestational weight gain. Conclusions for Practice Both maternal hyperglycemia and excessive weight gain have independent effects to increase childhood obesity risk. Future research should focus on prevention efforts during pregnancy as a potential window of opportunity to reduce childhood obesity.

Concepts: Nutrition, Insulin, Diabetes mellitus, Obesity, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Impaired glucose tolerance

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The prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age.

Concepts: Nutrition, Insulin, Middle Ages, Endocrinology, Glucose tolerance test, Impaired fasting glycaemia, Impaired glucose tolerance, Young adult

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Epidemiological evidence demonstrates the neuroendocrine link between stress, depression and diabetes. This study observed glucose intolerance of rats exposed to chronic unpredictable mild stress (CUMS) in oral glucose tolerance test (OGTT). CUMS procedure significantly up-regulated corticotropin-releasing factor (CRF)-related peptide urocortin 2 expression and elevated cAMP production, resulting in over-expression of suppressor of cytokine signaling 3 (SOCS3) in hypothalamic arcuate nucleus (ARC) of rats. Furthermore, SOCS3 activation blocked insulin signaling pathway through the suppression of insulin receptor substrate 2 (IRS2) phosphotyrosine and phosphatidylinositol-3-kinase (PI3-K) activation in hypothalamic ARC of CUMS rats after high-level of insulin stimulation. These data indicated that CUMS procedure induced the hyperactivity of CRF system, and subsequently produced conditional loss of insulin signaling in hypothalamic ARC of rats. More importantly, icariin and fluoxetine with the ability to restrain CRF system hyperactivity improved insulin signaling in hypothalamic ARC of CUMS rats, which were consistent with the enhancement of glucose tolerance in OGTT, showing anti-diabetic efficacy. Although effective in OGTT, anti-diabetic drug pioglitazone failed to restore hypothalamic ARC CRF system hyperactivity, paralleling with its inability to ameliorate the loss of insulin signaling and depression-like behavior in CUMS rats. These observations support the hypothesis that signal cross-talk between hypothalamic CRF system and insulin may be impaired in depression with glucose intolerance and suggest that icarrin and fluoxetine aiming at CRF system may have great potential in the prevention and treatment of depression with comorbid diabetes.

Concepts: Hypothalamus, Insulin, Diabetes mellitus, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Impaired glucose tolerance

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The carbohydrate deficit induced by exercise is thought to play a key role in increased post-exercise insulin action. However, the effects of replacing carbohydrate utilized during exercise on postprandial glycaemia and insulin sensitivity are yet to be determined. This study therefore isolated the extent to which the insulin-sensitizing effects of exercise are dependent on the carbohydrate deficit induced by exercise, relative to other exercise-mediated mechanisms. Fourteen healthy adults performed a 90-min run at 70% V ˙ O 2 max starting at 1600-1700 h before ingesting either a non-caloric artificially-sweetened placebo solution (CHO-DEFICIT) or a 15% carbohydrate solution (CHO-REPLACE; 221.4 ± 59.3 g maltodextrin) to precisely replace the measured quantity of carbohydrate oxidized during exercise. The alternate treatment was then applied one week later in a randomized, placebo-controlled, and double-blinded crossover design. A standardized low-carbohydrate evening meal was consumed in both trials before overnight recovery ahead of a two-hour oral glucose tolerance test (OGTT) the following morning to assess glycemic and insulinemic responses to feeding. Compared to the CHO-DEFICIT condition, CHO-REPLACE increased the incremental area under the plasma glucose curve by a mean difference of 68 mmol·L-1 (95% CI: 4 to 132 mmol·L-1; p = 0.040) and decreased the Matsuda insulin sensitivity index by a mean difference of -2 au (95% CI: -1 to -3 au; p = 0.001). This is the first study to demonstrate that post-exercise feeding to replaceme the carbohydrate expended during exercise can attenuate glucose tolerance and insulin sensitivity the following morning. The mechanism through which exercise improves insulin sensitivity is therefore (at least in part) dependent on carbohydrate availability and so the day-to-day metabolic health benefits of exercise might be best attained by maintaining a carbohydrate deficit overnight.

Concepts: Nutrition, Insulin, Diabetes mellitus, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Carbohydrate

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To create and validate an estimation formula for 2-h post-challenge plasma glucose (2-hPG) as an alternative to oral glucose tolerance test (OGTT) for impaired glucose tolerance (IGT) screening.

Concepts: Insulin, Diabetes mellitus, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Impaired glucose tolerance, Blood tests

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Sixteen plasma markers of inflammation and oxidative stress were measured during OGTT in 54 subjects. Leptin, RBP4, CRP, OPN, ANG, MDC, and MCSF concentrations significantly decreased during OGTT (P<0.05). IL6, IL8, and MCP3 concentrations significantly increased during OGTT (P<0.05). These results provide evidence that glucose ingestion affects systemic inflammation and oxidative stress.

Concepts: Insulin, Diabetes mellitus, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Impaired glucose tolerance, Reactive hypoglycemia

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Abstract Data on glucose metabolism in Asian adolescents with polycystic ovary syndrome (PCOS) are limited. Glucose metabolism assessment using an oral glucose tolerance test (OGTT) in obese and lean Thai adolescents with PCOS, and a comparison between the two groups were done. Thirty-one patients (19 obese, 12 lean) were enrolled. Their median (range) age was 14.9 (11.0-21.0) years. Eighteen patients had abnormal glucose metabolism (13 hyperinsulinemia, 4 impaired glucose tolerance, and 1 diabetes). Compared between obese [median (range) BMI Z-score, 1.6 (1.2-2.6)] and lean [median (range) BMI Z-score, 0.1 (-1.4 to 0.6)] patients, the frequencies of each abnormal OGTT category, areas under the curves of glucose and insulin levels, and insulinogenic index were not different; however, insulin resistance was greater in the obese group. In conclusion, a high proportion of our adolescents with PCOS had abnormal glucose metabolism. Therefore, OGTT should be performed in adolescents with PCOS for the early detection of abnormal glucose metabolism.

Concepts: Insulin, Diabetes mellitus, Endocrinology, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Impaired glucose tolerance

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In cystic fibrosis (CF) patients, elevations in 1 hr plasma glucose (PG1) during a 75 g oral glucose tolerance test are common, but of unclear long-term clinical relevance. Thus, we examined associations of PG1 with percent-predicted forced expiratory volume in 1 sec (FEV1 % predicted), CF exacerbations, and CF related diabetes (CFRD) development.

Concepts: Insulin, Diabetes mellitus, Blood sugar, Glucose tolerance test, Impaired fasting glycaemia, Insulin resistance, Cystic fibrosis, Impaired glucose tolerance