Differences In Fasting Glucose Research Articles

Associations between fasting glucose rate-of-change and the missense variant, rs373863828, in an adult Samoan cohort.

The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828. We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables. By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (β = -0.05 mmol/L/year per allele, p = 0.058 among women; β = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes. Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting.

Imparied insulin sensitivity in the early hours following either active or passive ascent to 3600m is associated with acute mountain sickness susceptibility

Reduced insulin sensitivity (a higher glucose level for the same insulin concentration) at baseline residence (BLR) has been associated with increased susceptibility to acute mountain sickness. (AMS) at high altitude (HA). The objective of this study was to determine whether fasting blood glucose (GLU), lactate (LAC) and insulin (INS) were impacted during an active versus passive ascent to 3600m in AMS-susceptible and AMS-resistant individuals. We hypothesized that insulin sensitivity would be reduced at BLR in the AMS-susceptible cohort based on previous research. To test this hypothesis, 78 active-duty Soldiers were tested at baseline residence (BLR), transported to Taos, New Mexico (2,845m), then hiked (n=39) or were driven (n=39) to 3600m, and stayed for four days. AMS-C was assessed using the Environmental Symptoms Questionnaire (ESQ) at HA twice on day 1, five times on days 2 and 3 and once on day 4. If AMS-C was ≥0.7 at any timepoint, individuals were categorized as AMS-susceptible (AMS+, n=33); others categorized as resistant (AMS−, n=45). Fasting rested blood GLU and LAC responses collected at 06:00 were measured using a blood gas analyzer and serum INS responses were measured using an ELISA assay at BLR, HA2 (14-h post-ascent), HA3 (38-h post ascent), and HA4 (62-h post ascent). An additional sample for blood GLU and LAC was collected on HA1 at 18:00 (2-h post ascent). As expected, the active compared to passive ascent group demonstrated an increase (p<0.05) in GLU (113.6±14.3 vs. 101.9±15.1) and LAC (2.56±0.93 vs. 1.73±0.78) on HA1 most likely due to sympathetic stimulation following active ascent. However, differences in fasting GLU and LAC between ascent groups did not persist on HA2 through HA4. There were also no ascent group differences INS in any of the conditions. Fasting GLU levels on HA2 were higher in the AMS+ vs. AMS− cohorts (99.8±9.8 vs 95.3±7.9 mg/dl; p<0.05) but fasting INS levels on HA2 did not differ between cohorts (9.8±5.4 vs.7.1±3.4 mIU/ml; p>0.05) indicating impaired insulin sensitivity in those susceptible to AMS early in the HA exposure. There were no differences, however, in GLU and INS levels between AMS+ vs. AMS− cohorts on BLR, HA3 or HA4. Fasting LAC also demonstrated no differences in any of the conditions in the active vs. passive ascent groups or AMS+ vs. AMS− cohorts. In conclusion, the increase in blood GLU and LAC at HA1 following active compared to passive ascent was expected. Contrary to our hypothesis, however, a reduction in insulin sensitivity was not found in AMS-susceptible individuals at BLR but was found at 14-h post ascent to 3600m and quickly resolved thereafter. The inability to effectively utilize glucose as an O2-effcient fuel in the early hours of HA exposure may contribute to AMS symptoms. USAMRDC. Authors’ views not offcial U.S. Army or DoD policy. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex-Specific Elevated Fasting Glucose in Patients with Major Depressive Disorder.

This study aimed to test whether the relationship between Major Depressive Disorder (MDD) and prediabetes is sex-specific and explored potential pathways. One hundred sixty-eight participants were enrolled, and 142 completed the study for data analysis. Participants were divided into patients with MDD (n=58) and without MDD, i.e., controls (n=84). The Oral Glucose Tolerance Test (OGTT) was conducted, and the serum cortisol levels of each participant were also measured. Demographic variables were analyzed using t-tests or chi-square tests. Covariance analysis was conducted to test the measures derived from OGTT and cortisol levels between groups. There was no difference in fasting glucose, 2-hour post-prandial levels, and indices of insulin sensitivity between MDD and control groups. However, in a stratified and sex-comparative analysis, female participants with MDD had higher fasting glucose and cortisol levels than female controls, but this was not seen in males. Also, fasting glucose was positively correlated with the severity of depression in females with MDD. Females with MDD have the highest risk of developing prediabetes compared to female controls and males, possibly through cortisol. Fasting glucose and cortisol could be biomarkers to recognize prediabetes in females with MDD for early intervention and better outcomes.

Denosumab Improves Glycaemic Parameters in Postmenopausal Osteoporosis Patients with Combined Type 2 Diabetes Mellitus.

This study aimed to determine whether RANKL inhibitors in postmenopausal osteoporosis patients with combined type 2 diabetes mellitus (T2DM) could improve their glucose metabolism index. First of all, 84 patients affected with postmenopausal osteoporosis with combined T2DM attending the Department of Endocrinology at the Third Hospital of Hebei Medical University were selected and randomized into two groups of 42 patients each. One group was given Denosumab 60 mg once every six months (denosumab group, D.G.), and the other group was given 2 mg ibandronate once every three months (ibandronate group, I.G.). Blood glucose parameters were compared before and after treatment in both groups and serum active GLP-1 levels and DPP-4 levels were also assessed. After treatment, there was no significant difference in fasting glucose between the two groups, but there was a significant decrease in fasting glucose in the Denosumab Group (D.G.) compared to before treatment. There was a significant difference in 2-hour postprandial glucose (2hPG) between the two groups after treatment, with the D.G. being lower than the ibandronate group (I.G.). Glycosylated haemoglobin (HbA1c) was lower in the D.G. than in the I.G. after treatment, but the difference between them was insignificant. In the D.G., serum active GLP-1 levels increased after treatment, and serum DPP-4 levels decreased. Serum GLP-1 and DPP-4 levels in the I.G. did not change compared with those before treatment. In conclusion, In the clinical management of postmenopausal osteoporosis patients with combined T2DM, the choice of RANKL inhibitors as anti-osteoporosis therapy may benefit their glycaemic parameters by elevating serum active GLP-1 levels and decreasing serum DPP-4 levels.

Association of blood pressure variability with target organ damage in older patients with essential hypertension.

Although multiple measures of blood pressure variability (BPV) have been proposed, whether they are better than mean blood pressure in predicting target organs is unclear. We aimed to determine the relationship between short term BPV and target organ injury. This study was a retrospective study, and 635 inpatients in the Department of Cardiology from 2015 to 2020 were selected. We divided participants into four groups on the basis of the quartiles of BPV. One-way analysis of variance was used to compare the differences between the groups, and linear regression was used to analyze the relationship between BPV and target organ damage. The average age of 635 patients was 74.36 ± 6.50 years old. Among them, 354 of 627 patientshad diminished renal function (56.5%), 221of 604 patients had associated left ventricular hypertrophy (36.6%), and 227 of 231 patients had carotid plaque formation (98.3%). The baseline data indicated significant differences in fasting glucose, total cholesterol, low-density lipoprotein, creatinine, glomerular filtration rate, sex, calcium channel blocker use, and the rate of diminished renal function. Multiple linear regression analysis showed that BPV was negatively correlated with renal injury (creatinine: r = 0.306, p < 0.01; estimated glomerular filtration rate: r = 0.058, p < 0.01), and BPV is positively correlated with cardiac injury (r = 0.083, p < 0.01). Elevated BPV was not found to be associated with vascular injury. Renal function decreases with increasing BPVand left ventricular mass increases with increasing BPV.

Comparative analysis of obesity prevalence, antioxidant and oxidant status in children with Down syndrome - asibling-controlled study.

Down syndrome (DS), acommon genetic disorder, leads to various physical, cognitive, and developmental challenges. The supplementary copy of chromosome 21 introduces an abundance of genes, which potentially can influence metabolic irregularities. The aim of the study is to conduct acomprehensive comparative assessment of oxidative stress indicators (TAS, TOS, OSI), BMI, fasting glucose, and insulin levels, HOMA-IR among children and adolescents with DS in contrast to their non-DS siblings. and the control group (CG) comprised 20 individuals, siblings of SG (mean age 15.92 years). Anthropometric measurements were conducted. TAS, TOS, fasting glucose, and insulin were assessed. BMI, BMI SDS, OSI and HOMA-IR were calculated. SG vs. CG: BMI - overweight (29,19% vs. 15%), obese (19,05% vs. 5%); TAS (1.92 mmol/l vs. 1.79 mmol/l (p=0.0015)); TOS (51.52mmol/l vs. 33.05 mmol/l (p=0.014)); OSI (2475.02 vs. 1949,75 (p=0.038)); no significant differences in fasting glucose, insulin and HOMA-IR. Statistically significant correlations in SG: TOS and BMI, BMI SDS, HOMA-IR; OSI and BMI, BMI SDS, HOMA-IR; HOMA-IR and BMI SDS; fasting insulin and BMI PC; in CG: TAS and BMI; fasting glucose and fasting insulin. The research results indicate differences in metabolic processes between the group of individuals with DS compared to the CG, despite shared environmental conditions. The presence of an additional copy of chromosome 21 may contribute to the occurrence of metabolic disorders. These findings emphasize the need for further research that will lead to abetter understanding of these relationships and contribute to the development of effective therapeutic strategies.

Maternal exercise shifts adiposity distribution in offspring towards energy burning brown fat

Human epidemiological and animal studies show the maternal in utero environment significantly impacts offspring development. This includes sedentary lifestyle, which is linked to developmental programming of metabolic dysfunction. The aim of this study was to investigate metabolic outcomes in offspring of sedentary mice versus mice that exercised in pregnancy. C57BL/6J female mice were placed on control diet and allocated to sedentary (SED) versus voluntary running wheel exercise (EX) cages. Voluntary wheel running was allowed 2 weeks prior to breeding and throughout weaning. Offspring underwent body composition measurement and insulin and glucose tolerance tests at 6 and 12 weeks of age, were placed in an indirect calorimetry system to assess energy balance at 14 weeks, and were euthanized for collection of adipose depots at 16 weeks. Outcomes were analyzed by two-way ANOVA to assess effects of exercise, sex, and their interaction. We studied metabolic function in 11 male SED, 13 female SED, 15 male EX, and 13 female EX offspring. While body mass and adiposity were similar among groups, EX mice had less subcutaneous white adipose (% body mass: 1.26±0.09 male SED vs. 0.87±0.06 male EX vs. 1.15±0.11 female SED vs. 0.95 ±0.04 female EX; PSex=0.871, PEX=0.001, PInt=0.237) and more brown adipose (% body mass: 0.31±0.03 male SED vs. 0.47±0.05 male EX vs. 0.27±0.02 female SED vs. 0.48 ±0.05 female EX; PSex=0.704, PEX=0.001, PInt=0.527). There were no differences in fasting glucose and insulin levels, insulin sensitivity, glucose tolerance, or measures of energy balance (e.g., food intake, energy expenditure) among groups. These data suggest that despite no change in overall body mass or body composition, maternal exercise shifts adiposity distribution of offspring away from energy storing white fat towards energy burning brown fat. This change may impact energy metabolism over the lifespan given increasing evidence for advantageous metabolic adaptations with increased brown fat.

Comparison of midlife offspring cohorts based on family history of Alzheimer’s Disease: multi‐domain risk factors and cognitive function

AbstractBackgroundMaintaining healthy clinical indicators and behavior is positively related to cognitive protection from midlife. However, limited population‐based studies have explored the role of family history on these factors in midlife. Therefore, we examined cognitive‐related risk factors in two midlife cohorts from the same source population in the Age, Gene/Environment Susceptibility‐Reykjavik Study.MethodWe included 446 offspring (aged 61, 49% women) from the random sample (RS) without Alzheimer’s Disease (AD) and 499 offspring (aged 63, 49% women) to AD cases at baseline and during follow up from the main study. Accordingly, we labeled the offspring with and without AD family history as offspring AD and offspring RS, respectively. Clinical factors included BMI, systolic (SBP) and diastolic blood pressure (DBP), cholesterol, fasting glucose, inflammatory factors, and medication. Socio‐behavioral factors included education, smoking, problems of doing usual activities. Cognitive function was evaluated by MMSE and STROOP. To address the potential correlation between siblings within one family, we compared these characteristics with the random effects intercept mixed model by family ID. We also did a sensitivity analysis by comparing people under age 65 to assess reverse causation for specific traits. All models were adjusted for age and sex. Fasting glucose, triglycerides, and inflammatory factors were log‐transformed due to skewness. We consider p&lt;0.05 as statistically significant.ResultAs shown in the table, socio‐behavioral factors, cognitive function, or most clinical characteristics did not differ in the two groups. The Offspring AD had 2.71‐unit lower SBP and 0.03‐unit higher log(glucose) (3% increased glucose) than the RS (p&lt;0.05). The sensitivity analysis among people under age 65 showed a similar pattern, except for the insignificant difference in fasting glucose between offspring AD and RS.ConclusionIn general, there was no difference in AD‐related health profile among midlife offspring with and without AD family history. This analysis of standard cardiovascular and cognitive impairment‐related risk factors suggests that these variables alone will not help identify at‐risk individuals for later‐life cognitive impairment.

Comparison of the Concordance of Cardiometabolic Diseases and Physical and Laboratory Examination Findings between Monozygotic and Dizygotic Korean Adult Twins: A Cross-Sectional Study Using KoGES HTS Data.

This study investigated the contribution of genetic and environmental factors to cardiometabolic diseases (CMDs) by comparing disease concordance in monozygotic and dizygotic twins. This cross-sectional study analyzed 1294 (1040 monozygotic and 254 dizygotic) twin pairs (&gt;20 years) based on the Korean Genome and Epidemiology Study data (2005-2014). The odds ratios of disease concordance were calculated using binomial and multinomial logistic regression models. The occurrence of CMDs (hypertension, hyperlipidemia, type 2 diabetes, cerebral stroke, transient ischemic attack, and ischemic heart disease) and related physical and laboratory levels did not differ between the monozygotic and dizygotic twin groups. The odds for concordance of the presence/absence of CMDs and the likelihood of incident CMD within monozygotic twins were comparable to that of dizygotic twins. The absolute differences in hemoglobin A1c, insulin, low- and high-density lipoprotein cholesterol, total cholesterol, triglycerides, and systolic blood pressure were lower in monozygotic twins than in dizygotic twins. Absolute differences in fasting glucose and diastolic blood pressure did not differ between groups. Although baseline levels of several laboratory parameters related to CMD showed a strong likelihood of heritability in monozygotic twins, CMD phenotype appears to be largely affected by environmental factors.

ODP004 Glucose Profiles and Insulin Sensitivity in Adults with Overweight/Obesity Participating in a Weight Loss Intervention based on Early Time-Restricted Eating plus Daily Caloric Restriction vs Daily Caloric Restriction Alone

Abstract Background Emerging literature suggests that short-term (&amp;lt;1 week) time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity, but few studies have evaluated the longer-term effects of TRE on glycemic outcomes. The aim of this study was to compare 24-hour glucose profiles and insulin sensitivity in participants enrolled in a 12-week behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Methods Eighty-one adults with overweight or obesity (age 18-50 years, BMI 27-45 kg/m 2) were randomized to E-TRE (10-hour eating window starting within 3 hours of waking) plus DCR (35% daily caloric restriction) or DCR alone for 12 weeks. Each participant wore a continuous glucose monitor (CGM, Freestyle Libre Pro) for 7 days at baseline and week 12. Fasting glucose and insulin levels were drawn for assessment of insulin sensitivity by homeostasis model assessment-estimated insulin resistance (HOMA-IR) at baseline and week 12. Analysis of Covariance (ANCOVA) was used to assess whether there were differences in glucose measures by randomized group. Between-group differences in minutes spent over glucose of 120 mg/dL and excursions over glucose of 120 mg/dL were assessed using either negative binomial or Poisson regression. All models were adjusted for the change in weight from baseline to week 12. Results Of the 81 adults randomized, 45 participants had valid CGM data and 40 had valid glucose, insulin and HOMA-IR data at baseline and 12 weeks (missing data due to COVID-19 related restrictions on in person research). There were no significant differences in sex, age, BMI or percent with prediabetes between groups (88% female, age 39.2 +/- 6.9 years, BMI 33.8 +/- 5.7 kg/m 2, 17% with prediabetes). After adjusting for weight loss, there were no between-group differences in overall average sensor glucose, minutes spent above 120 mg/dL, number of glucose excursions above 120 mg/dL, daytime or nighttime average sensor glucose, mean amplitude of glycemic excursions, or standard deviation or coefficient of variation of glucose levels. There was a significant difference in week 12 day-night sensor ratio between the two groups, with those in the E-TRE+DCR group having day-night sensor ratio mean 0.27 (95% confidence interval -0.53, -0. 00) units lower on average than those in the DCR group at week 12, adjusting for baseline. There were no between-group differences in fasting glucose, insulin, or HOMA-IR. Conclusions While the E-TRE+DCR group had a slightly lower day-to-night sensor ratio compared to the DCR group, this difference is likely not clinically meaningful because there were no observed differences in day or night average sensor glucose. Because participants with diabetes were excluded and only 17% of participants had prediabetes, our ability to detect changes in glucose profiles and insulin sensitivity may have been limited. Presentation: No date and time listed

Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes.

BackgroundIn contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.MethodsA prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.ResultsThere was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.ConclusionsLinagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.

Effect of Optimizing Fiber Intake of Mice on Weight Gain, Fat Mass, Oral Glucose and Insulin Tolerance Tests in Mice Fed a High Fat Diet

ObjectivesIn humans, fiber intakes close to recommended levels (14g/1000 kcal, Institute of Medicine (IOM)) are associated with less chronic disease. In most semi-purified rodent diets, the only fiber source is cellulose. The main objective of this work was to determine if substituting a complex fiber blend for cellulose would affect metabolism of mice fed a 45% kcal from fat diet.MethodsTo model a recommended human fiber profile for rodents, the relative proportions of cellulose, hemicellulose, lignin, pectin and beta-glucan were estimated from a one-day meal plan with the recommended fiber level using a food fiber composition database. Subsequently, a mix of oat hull fiber, pectin and beta-glucan was added to a high-fat rodent diet at the typical US intake or at the recommended level (8 g/1000kcal (low), 14 g/1000 kcal (high)). Three groups of C57Bl/6 mice (n = 12) were fed the experimental diets for 16 weeks. The third diet was also high fat but only contained cellulose. Body composition was measured by MRI at weeks 7 and 14. Oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), were conducted at weeks 8 and 15 (OGTT) and week 16 (ITT).ResultsThere were no differences in final weight or weight gain in mice between the groups. There was a trend for mice fed the low complex fiber profile diet to have a higher body fat percentage than mice fed the other groups (p = 0.08). However, there were no differences in fasting glucose at week 8 or 15, and no significant differences in OGTT or ITT between the groups.ConclusionsRodent models are used extensively to investigate the role of nutrients in maintaining metabolic health and the prevention of chronic disease. These results indicate that exogenous fiber added to a high fat, semi-purified rodent diet does not improve body composition or glucose metabolism in mice.Funding SourcesThe National Institute of Food and Agriculture (NIFA).

Early supplementation of folate and vitamin B12 improves insulin resistance in intrauterine growth retardation rats.

Insulin sensitivity is changed during the neonatal period in small for gestational age (SGA) infants. Yet, the interventional strategies are still limited. We aimed to investigate the effects of supplementation with high folate and vitamin B12 diets in the early postnatal period on the changes in insulin sensitivity in an intrauterine growth retardation (IUGR) rat model. IUGR rat model was established by both low-protein diet feeding and daily diet restriction. High folate and vitamin B12 diet was supplied in IUGR as nutritional interventional group (IUGR-I), otherwise, the non-intervened IUGR group (IUGR-NI). In this study, male rats were studied in order to avoid hormonal and gender influence. At 21, 60 and 120 days, fasting plasma glucose, insulin, triglyceride, cholesterol, and homocysteine levels were measured among the control, IUGR-I, and IUGR-NI groups. Pearson analysis was used to evaluate the correlation between homocysteine and fasting blood glucose, insulin, HOMA-IR, triglyceride, and cholesterol levels. We established IUGR rat model by both low protein and restricted diet feeding during pregnancy and the incidence of IUGR pups was 93.33%. There was no difference in fasting glucose, insulin, HOMA-IR, triglyceride and cholesterol levels between the control, the IUGR-NI and the IUGR-I group at day 21. At day 60, insulin, HOMA-IR and triglyceride levels in the IUGR-I group were remarkably lower than those in the IUGR-NI group, but still higher than those in the control group (F=38.34, P=0.02; F=49.48, P=0.02; F=17.93, P<0.001, respectively). At day 120, glucose, insulin, HOMA-IR and Hcy levels in the IUGR-I group were obviously lower than those in the IUGR-NI group, although still higher than those in the control group (F=21.60, P<0.001; F=164.46, P<0.001; F=75.15, P<0.001; F=35.46, P<0.001, respectively). There were no significant differences in triglyceride and cholesterol levels between the IUGR-I group and the control group at day 120. At 120-day, homocysteine in IUGR-I group was highly positively correlated with fasting glucose and HOMA-IR (r=0.863, P=0.006; r=0.725, P=0.042, respectively); Only homocysteine was positively correlated with fasting glucose in IUGR-NI group (r=0.721, P=0.044). Early supplementation of folate and vitamin B12 improved insulin resistance and lipid levels in IUGR rats to some extent, along with decreasing homocysteine levels, but not enough to completely repair glucose and lipid metabolism.

Impact of preconception weight loss on fasting glucose and pregnancy outcomes in women with obesity: A randomized trial.

This study examined the effectiveness of a nonsurgical, preconception weight loss intervention on pregnancy outcomes in women with obesity. This was a two-arm, parallel-group randomized controlled trial. A total of 164 women with BMI 30 to 55kg/m2 who were aged 18 to 38 years and planning pregnancy were randomized to a 12-week standard dietary intervention (SDI; n=79) or a modified very low-energy diet (VLED; n=85). Participants were observed for ≤48 weeks while trying for pregnancy and then during pregnancy. The primary outcome was maternal fasting plasma glucose at 26 to 28 weeks' gestation. Exploratory outcomes were individual and composite obesity-related adverse pregnancy outcomes. Weight loss was greater in the VLED group (SDI 3.2 [0.6] kg vs. VLED 13.0 [0.5] kg, p<0.01). In completers who had a singleton live birth (SDI 22/79 vs. VLED 35/85, p=0.10), there was no difference in fasting glucose at 26 to 28 weeks' gestation (SDI 4.8[0.2] mmol/L vs. VLED 4.6 [0.1] mmol/L, p=0.42). However, the composite of adverse pregnancy outcomes was significantly lower in the VLED group (p<0.001). Substantial prepregnancy weight loss in women with obesity does not alter fasting glucose at 26 to 28 weeks' gestation but does reduce a composite of adverse pregnancy outcomes. A better understanding of metabolic changes in pregnancy after preconception weight loss may assist in improving maternal and neonatal health outcomes.

Carbonyl Reductase 1 Overexpression in Adipose Amplifies Local Glucocorticoid Action and Impairs Glucose Tolerance in Lean Mice

Glucocorticoids play a critical role in metabolic homeostasis. Chronic or excessive activation of the glucocorticoid receptor (GR) in adipose tissue contributes to metabolic disorders such as glucose intolerance and insulin resistance. Steroid-metabolising enzymes in adipose, such as 11β-HSD1 or 5α-reductase, modulate the activation of GR by converting primary glucocorticoids into more or less potent ligands. Carbonyl reductase 1 (CBR1) is a novel regulator of glucocorticoid metabolism, converting corticosterone/cortisol to 20β-dihydrocorticosterone/cortisol (20β-DHB/F); a metabolite which retains GR activity. CBR1 is abundant in adipose tissue and increased in obese adipose of mice and humans1 and increased Cbr1 expression is associated with increased fasting glucose1. We hypothesised that increased Cbr1/20β-DHB in obese adipose contributes to excessive GR activation and worsens glucose tolerance. We generated a novel murine model of adipose-specific Cbr1 over-expression (R26-Cbr1Adpq) by crossing conditional knock-in mice with Adiponectin-Cre mice. CBR1 protein and activity were doubled in subcutaneous adipose tissue of male and female R26-Cbr1Adpq mice compared with floxed controls; corresponding to a two-fold increase 20β-DHB (1.6 vs. 4.2ng/g adipose; P=0.0003; n=5-7/group). There were no differences in plasma 20β-DHB or corticosterone. Bodyweight, lean or fat mass, did not differ between male or female R26-Cbr1Adpq mice and floxed controls. Lean male R26-Cbr1Adpq mice had higher fasting glucose (9.5±0.3 vs. 8.4±0.3mmol/L; P=0.04) and worsened glucose tolerance (AUC 1819±66 vs. 1392±14; P=0.03). Female R26-Cbr1Adpq mice also had a worsened glucose tolerance but fasting glucose was not altered with genotype. There were no differences in fasting insulin or non-esterified fatty acid between genotypes in either sex. Expression of GR-induced genes Pnpla2, Gilz and Per1, were increased in adipose of R26-Cbr1Adpq mice. Following high-fat diet induced obesity, no differences in bodyweight, lean or fat mass, with genotype were observed in male and female mice, and genotype differences in fasting glucose and glucose tolerance were abolished. In conclusion, adipose-specific over-expression of Cbr1 in lean male and female mice led to increased levels of 20β-DHB in adipose but not plasma, and both sexes having worsened glucose tolerance. The influence of adipose CBR1/20β-DHB on glucose tolerance was not associated with altered fat mass or bodyweight and was attenuated by high-fat diet-induced obesity. These metabolic consequences of Cbr1 manipulation require careful consideration given the wide variation in CBR1 expression in the human population, the presence of inhibitors and enhancers in many foodstuffs and the proposed use of inhibitors as an adjunct for cancer treatment regimens. Reference: Morgan et al., Scientific Reports. 2017; 7.

Insulin receptor (InsR) deletion from renal tubule reduces kidney size and upregulates gluconeogenic capacity of the proximal tubule in mice

Insulin has been demonstrated to have a number of important actions in the kidney, including activation of transport, growth, and inhibition of proximal tubule (PT) gluconeogenesis. Metabolic syndrome (MetS) is associated with down-regulation of the abundance of insulin receptor (InsR) and early signaling. Previously, we found evidence of elevated renal gluconeogenesis in PT-select (non-inducible, deleted from birth) InsR KO mice. Whether development of the kidney was affected from birth in those mice was uncertain. In this study, we determine whether deletion of the InsR (in adult mice) from the whole-renal tubule using Paired Box 8 (PAX-8) targeting of tetracycline-inducible cre-recombinase (Cre) in floxed InsR-harboring mice, affects glucose homeostasis. Male (M) and female (F) Cre+ and Cre- mice (8-months old) were treated with doxycycline (DOX) in the diet for 2 weeks (to KO the InsR in the Cre+ mice, n = 9-12 mice/group). Fasting (18-hr) and refed (2-hr) glucose were obtained in the baseline, 10, and 45 days post-DOX treatment. Ten- and 45-day refed blood glucoses were significantly higher in M, but not F, KO (relative to their, respective WT). No differences in fasting glucose were observed. At 8-weeks (post-DOX), mice were fasted overnight (to upregulate gluconeogenesis), then provided a meal 3 hours prior to euthanization to raise endogenous insulin. No genotype effect on final body weight was found; however, kidney weights were lower (p = 0.01 for genotype) in the KO, especially in males (g, mean ± sem): 0.189±0.003 (WTM); 0.165 ± 0.006 (KOM); 0.142 ± 0.002 (WTF); 0.137 ± 0.006 (KOF). We developed an approach to measure glucose production in the medium of PT-suspensions harvested upon euthanasia. Suspended PT were aliquoted to receive 1 of 3 treatments for a 1 hour incubation: 1) vehicle (0 glucose containing Dulbecco's modified medium); 2) vehicle containing cyclic AMP (cAMP) and dexamethasone (DEXA); and 3) cAMP+DEXA+ 5000 pM insulin. Glucose in the media was measured by Amplex Red. Three-way ANOVA revealed significant effects of genotype (p = 0.033), sex (p = 0.048), and PT treatment (p = 0.0047) on glucose production. PT harvested from KO males produced the most glucose, and insulin reduced glucose production in all groups (% decrease versus vehicle): 43, 18, 29, 48 in WTM, KOM, WTF, and KOF, respectively. Surprisingly, DEXA and cAMP did not stimulate glucose production, as expected, which may represent differential regulation relative to liver. Remaining sensitivity of KO PT to insulin may be the result of insulin binding to insulin-like-growth factor receptors, which has been observed in humans with InsR mutations. Overall, these results demonstrate that deletion of the InsR from kidney tubular epithelium in adulthood reduces the size of the kidney, results in post-prandial relative hyperglycemia, and elevated glucose producing capacity in PT. This supports a non-redundant role for PT-InsR signaling in whole-body glucose homeostasis.

The effect of pilates on metabolic control and oxidative stress of diabetics type 2 – A randomized controlled clinical trial

IntroductionThe Pilates method is an approach to body and mind exercises that has as its foundation the gain of stability, strength and flexibility, and the work of muscular control, posture and breathing, which can generate repercussions on oxidative stress and ROS production, it is expected that Pilates can satisfactorily influence glycemic and oxidative stress reduction in elderly diabetes. AimTo analyze the effect of a Pilates protocol on variables indicative of metabolic control and oxidative stress in patients with Type 2 Diabetes Mellitus. MethodRandomized clinical trial in type 2 diabetics enrolled in Hiperdia Parnaíba. A Pilates protocol was performed for 8 weeks, with 2 weekly consultations. The tested variables were: blood glucose, glycated hemoglobin, lipid profile, C-reactive protein and malondialdehyde. ANOVA tests, correlation of Wilcoxon, Friedman and Spearman, were used, with a significance level of 5%. Results44 diabetics participated in the study (intervention group: 22; control: 22), with a mean age of 61.23 ± 8.49years, the majority being female (77.3%), married (59.1%), literate (31.8%), with an average BMI of 26.96 ± 4.35 kg/m2. When analyzing the effects of the protocol, there was a significant reduction in glycated hemoglobin (p = 0.002) and oxidative stress (p = 0.004) in the intervention group, however, there were no differences in fasting glucose (p = 0.055) and in the profile lipid, expressed by the total cholesterol (p = 0.654), HDL (p = 0.591), LDL (p = 0.564) and triglycerides (0.192). There was a moderate positive correlation between oxidative stress and glycated hemoglobin (r = 0.44, p = 0.000). Conclusion: The exercise protocol based on the Pilates method produced a reduction in glycated hemoglobin and oxidative stress.

Persistent organic pollutants and maternal glycemic outcomes in a diverse pregnancy cohort of overweight women

BackgroundAnimal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women. MethodsA cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks’ gestation; range = 10–24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs). ResultsStudy participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: −0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor. DiscussionPrenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

Trajectories in estimated glomerular filtration rate in youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study.

We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes. We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiDCr-CysC equation to estimate GFR and categorized 'rising' and 'declining' eGFR as an annual change of ≥3 ml/min/1.73 m2 in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR. Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index. Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

Mediterranean Diet Adherence and Its Association with Cardiometabolic Factors in College Students

Abstract Objectives Adherence to a Mediterranean Diet (MD) is related to a reduced risk of chronic disease, however, there is limited research related to the MD in young adults. Our objective was to examine MD adherence in a sample of undergraduate college students ages 18–24 and explore its association with cardiometabolic factors. Methods Data (n = 3117, 67% female) were collected between 2012–18 from the College Health and Nutrition Assessment Survey, an on-going, cross-sectional study at a midsized, northeastern university. Dietary and nutrient data were obtained from three-day food records; 2 items from an online questionnaire were used to evaluate fish and alcohol consumption. A modified MD scoring tool examined intake of 9 dietary components; scores ranged from low to high (0–9). MD scores were further divided into 3 categories (low, med, high MD). Anthropometric, biochemical, and clinical measures were obtained in the fasted state and used to examine cardiometabolic risk factors. Mean differences according to MD categories were evaluated via ANCOVA with the use of age, gender, year, semester, daily kcals, and BMI as covariates. Results Most students were categorized as consuming a low MD (40.4%) or med MD (40.1%); only 19.4% were categorized as having a high MD score. Modest but favorable differences in fasting glucose (87.6 ± .4, 86.9 ± .4, 85.5 ± .6, mg/dL P &amp;lt; .02) and diastolic blood pressure were observed (71.6 ± .3, 70.8 ± .3, 69.9 ± .5, mm Hg P &amp;lt; .01) with increasing levels of MD adherence categories, respectively. No differences in fasting triglycerides, HDL-C, waist circumference, or systolic blood pressure were observed between groups of MD adherence. Conclusions Our findings suggest the MD may be linked to some favorable health parameters in young adults. Understanding the relationship between different dietary patterns and development of chronic disease in this population will optimize interventions aimed at reducing disease burden. Funding Sources New Hampshire Agriculture Experiment Station and USDA National Institute of Food and Agriculture Hatch Project 1,010,738.