Fasting Insulin Concentrations Research Articles

Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice

BackgroundType 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PurposeThe aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. MethodsA T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid β-protein (Aβ) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. ResultsTreatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aβ, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). ConclusionMlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study

BackgroundType 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population.MethodsThis was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1β and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes.ResultsPrediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1β and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1β and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05).ConclusionsSFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

Among Other Tissues, Short-Term Garlic Oral Treatment Incrementally Improves Indicants of Only Pancreatic Islets of Langerhans Histology and Insulin mRNA Transcription and Synthesis in Diabetic Rats.

The source, mRNA transcription, and synthesis of insulin in the pancreas, in addition to the bile duct and liver, in streptozotocin (STZ)-induced diabetic rats (DR) in response to garlic oral treatment are not yet clear. This study investigated the accumulative effects of continued garlic oral treatment on changes in the pancreas, bile duct, and liver with regards to: 1-Insulin mRNA transcription, synthesis, and concentration in relation to changes in serum insulin (SI); 2-Insulinogenic cells insulin intensity and distribution, proliferation, and morphology. Fasting blood glucose (FBG) and insulin concentration in serum and pancreas (PI) and sources and mRNA transcription in the pancreas, bile duct, and liver in normal rats given normal saline (NR-NS) and DR given either NS (DR-NS) or garlic extract (DR-GE) before and after 1, 4, and 8 weeks of oral treatment were examined. Compared to NR-NS, DR-NS showed a significant increase in FBG and reductions in SI and PI and deterioration in islets histology, associated pancreatic insulin numerical intensities, and mRNA transcription. However, compared to DR-NS, the targeted biochemical, histological, and genetic variables of DR-GE were significantly and incrementally improved as garlic treatment continued. Insulin or its indicators were not detected either in the bile duct or the liver in DR-GE. 8 weeks of garlic oral treatment is enough to incrementally restore only pancreatic islets of Langerhans insulin intensity and insulinogenic cells proliferation, morphology, and distribution. These indices were associated with enhanced pancreatic insulin mRNA transcription and synthesis. Eight weeks of garlic treatment were not enough to stimulate insulinogenesis in either the bile duct or the liver.

Direct and indirect effects of adiposity on markers of autonomic nervous system activity in older adults.

Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI = .036, .066), comparative fit index = .970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (β = 0.208, p = 0.018) and indirect (β = -.217, p = .041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (β = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (β = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults.

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk

BackgroundConsiderable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. ObjectiveThe purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. MethodsSecondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. ResultsOf the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = −0.494; P = 0.086) and insulin concentrations (r = −0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = −0.642; P = 0.024) and β cell function (r = −0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. ConclusionsThese data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight.This study was registered at clinicaltrials.gov as NCT02614729.

Copper Deficiency Associated with Glycemic Control in Individuals with Type 2 Diabetes Mellitus.

Adequate copper (Cu) status has been associated with improved glycemic control, partly because of its role in reducing oxidative stress through superoxide dismutase (SOD) activity. Thus, the aim was to investigate the relationship between plasma Cu concentration and markers associated with glycemic control in individuals with type 2 diabetes mellitus (T2DM). This observational and cross-sectional study was conducted in individuals with T2DM of both sexes, aged between 19 and 59years. Plasma Cu levels were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES). Fasting glucose and insulin concentrations, C-peptide levels, SOD activity, and glycated hemoglobin (%HbA1c) were measured. Homeostatic model assessments (HOMA%B, HOMA%S, and HOMA-IR) were also performed. Additionally, %body fat and waist circumference were measured, and body mass index was calculated. Participants were categorized based on their plasma Cu concentrations (< 70µg/dL and ≥ 70µg/dL). The associations between variables were analyzed using chi-squared or Fisher's test and binary logistic regression models. Statistical significance was set at P < 0.05. Of the 97 participants (74.2% women), 85.5% had Cu deficiency. Cu-deficient individuals showed elevated C-peptide concentrations and HOMA%B values compared to those with adequate Cu levels (2.8ng/mL vs. 1.8ng/mL, P = 0.011; and 71.4 vs. 31.0, P = 0.003), respectively. Cu deficiency was associated with insulin resistance (P = 0.044) and decreased likelihood of exceeding the target serum glucose level (OR = 0.147, P = 0.013). However, no significant association was found between SOD activity and plasma Cu concentration. Consequently, Cu deficiency was linked to improved glycemic control, although it was not associated with the other markers.

A randomised double-blind placebo-controlled trial of a probiotic combination for manipulating the gut microbiota and managing metabolic syndrome

An increasing number of studies indicate that the occurrence of metabolic syndrome is significantly influenced by the host's gut microbiota and its metabolites. This study evaluated the potential application of a combination of Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631 for the clinical remission of metabolic syndrome. This research comprised 40 individuals with metabolic syndrome, 21 of whom were in the probiotic intervention group and 19 in the placebo control group. The intervention duration was 11 weeks and involved the daily intake of 1 × 1010 CFU of a probiotic combination comprising Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631. The serum biochemical indexes of the participants before and after the intervention were measured. After the intervention, faecal samples were collected to comprehensively analyse the gut microbiota of the participants by high-throughput sequencing and the faecal concentrations of target short-chain fatty acids by gas chromatography–mass spectrometry. The results showed that the 11-week probiotic intervention significantly reduced fasting blood glucose, fasting insulin, triglyceride, and low-density lipoprotein cholesterol concentrations in patients with metabolic syndrome and significantly increased the abundance of Bacteroidetes and some genera that produce short-chain fatty acids by regulating the abundance of gut microbial taxa that are strongly correlated with the clinical indicators of metabolic syndrome. These results demonstrated the beneficial effects of the probiotic combination on the clinical remission of metabolic syndrome, suggesting its potential application as an adjuvant strategy for the clinical treatment of metabolic syndrome in the future and laying a foundation for the further study of the mechanism of action of probiotics in alleviating metabolic syndrome.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Modelling the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity in a cohort of Australian adults

Dietary guidelines are increasingly promoting plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons(1). It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. Here, we modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55% female) from the Childhood Determinants of Adult Health (CDAH) study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using food frequency questionnaires: CDAH-1 (2004–06), CDAH-2 (2009–11), and CDAH-3 (2017–19). The median follow-up duration was 13 years. The cumulative average intake of each food group was calculated to reflect habitual consumption. Insulin sensitivity (%) was estimated from fasting glucose and insulin concentrations at CDAH-3 (aged 39–49 years) using homeostasis model assessment. Applying the partition model(2), we simulated the replacement of one food group with another by including both in the model simultaneously (e.g., red meat and legumes), along with potential confounders and energy intake. The difference between parameter estimates (i.e., regression coefficients and variances) and their covariance were used to estimate the “substitution” effect. We report the simulated percentage point change in log-transformed insulin sensitivity for a 1 serve/day lower intake of one food group with a 1 serve/day higher intake of another food group. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 0·10, 95% CI 0·04–0·16). Adjustment for waist circumference attenuated this association by 61·4%. On an individual basis, replacing red meat with legumes (β = 0·12, 95% CI 0·02–0·21), nuts and seeds (β = 0·15, 95% CI 0·06–0·23), or whole grains (β = 0·11, 95% CI 0·04–0·17) was likewise associated with higher insulin sensitivity. Point estimates were similar when replacing processed meat with plant-based alternatives, but more uncertain due to wide confidence intervals. Our modelling suggests that habitually replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity, and thus, a lower risk of type 2 diabetes. Abdominal adiposity was identified as a potentially important mediator in this relationship. In relation to insulin sensitivity, our findings support the recommendation to choose plant-based sources of protein at the expense of red meat consumption.

Cluster analysis based on fasting and postprandial plasma glucose and insulin concentrations

Cluster analysis based on fasting and postprandial plasma glucose and insulin concentrations

Study the Association of Fat Mass and Obesity-associated (FTO) Gene Polymorphisms (SNP rs9939609) with Biochemical Markers in Obese Iraqi Patients

This study aimed to evaluate the association of single nucleotide polymorphisms (SNP rs-9939609) of the fat mass and obesity-associated (FTO) gene with body mass index (BMI) and some biochemical markers in obese patients. The fat and mass obesity (FTO) gene variant specific single nucleotide polymorphism (SNP rs-9939609) with the T to A missense mutation may have a powerful association with obesity. This case-control study included 106 obese patients (57 males and 49 females) and 80 healthy control (40 males and 40 females). DNA was extracted from whole blood, and then the tetra-primer amplification refractory mutation system - polymerase chain reactions (ARMS.PCR) technique was used to limit the single nucleotide gene polymorphisms (rs9939609) of the FTO gene. Lipid profile, glycated hemoglobin (HbA1C), fasting blood sugar, insulin and FTO concentrations were measured by standard methods. In this study, the A allele in the rs9939609 was at a higher frequency of 35 (33.1%) in the obese patients and at a significant p-value = 0.039 compared with control 15 (18.7%). It significantly increased in the additive model and allele frequency (p= 0.003, 0.002 respectively). The rs9939608 SNP showed a significant association with increased BMI, insulin and homeostatic model assessment-insulin resistance (HOMO-IR) with p-values of 0.001, 0.001 and 0.028 respectively. After making adjustments for age and sex, lower levels of high-density lipoprotein (HDL) were observed in the AA and TA genotypes compared to the TT genotype (p = 0.004). While, no significant differences were recorded between the rs9939608 SNP and HbA1C, total cholesterol (TC), triglyceride (TG), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) in obese patients

Effect of preoperative oral carbohydrates on insulin resistance in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial

PurposeThe present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients.MethodsA total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2–4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data.ResultsAt T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3.ConclusionAdministering either 200 mL or 400 mL of carbohydrates 2–4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients.Trial registrationChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn.

Continuous glucose monitoring captures glycemic variability in obesity after sleeve gastrectomy: A prospective cohort study.

HbA1c is an insensitive marker for assessing real-time dysglycemia in obesity. This study investigated whether 1-h plasma glucose level (1-h PG) ≥155mg/dL (8.6mmol/L) during an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) measurement of glucose variability (GV) better reflected dysglycemia than HbA1c after weight loss from metabolic and bariatric surgery. This was a prospective cohort study of 10 participants with type 2 diabetes compared with 11 participants with non-diabetes undergoing sleeve gastrectomy (SG). At each research visit; before SG, and 6weeks and 6months post-SG, body weight, fasting lipid levels, and PG and insulin concentrations during an OGTT were analyzed. Mean amplitude of glycemic excursions (MAGE), a CGM-derived GV index, was analyzed. The 1-h PG correlated with insulin resistance markers, triglyceride/HDL ratio and triglyceride glucose index in both groups before surgery. At 6months, SG caused 22% weight loss in both groups. Despite a reduction in HbA1c by 3.0±1.3% in the diabetes group (p<0.01), 1-h PG, and MAGE remained elevated, and the oral disposition index, which represents pancreatic β-cell function, remained reduced in the diabetes group when compared to the non-diabetes group. Elevation of GV markers and reduced disposition index following SG-induced weight loss in the diabetes group underscores persistent β-cell dysfunction and the potential residual risk of diabetes complications.

A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis.

The widely used dynamic disposition index, derived from oral glucose tolerance testing, is an integrative measure of the homeostatic performance of the insulin-glucose feedback control. Its collection is, however, time consuming and expensive. We, therefore, pursued the question if such a measure can be calculated at baseline/fasting conditions using plasma concentrations of insulin and glucose. A new fasting-based disposition index (structure parameter inference approach-disposition index [SPINA-DI]) was calculated as the product of the reconstructed insulin receptor gain (SPINA-GR) times the secretory capacity of pancreatic beta cells (SPINA-GBeta). The novel index was evaluated in computer simulations and in three independent, multiethnic cohorts. The objectives were distribution in various populations, diagnostic performance, reliability and correlation to established physiological biomarkers of carbohydrate metabolism. Mathematical and in-silico analysis demonstrated SPINA-DI to mirror the hyperbolic relationship between insulin sensitivity and beta-cell function and to represent an optimum of the homeostatic control. It significantly correlates to the oral glucose tolerance test based disposition index and other important physiological parameters. Furthermore, it revealed higher discriminatory power for the diagnosis of (pre)diabetes and superior retest reliability than other static and dynamic function tests of glucose homeostasis. SPINA-DI is a novel simple reliable and inexpensive marker of insulin-glucose homeostasis suitable for screening purposes and a wider clinical application.

Serum expression levels of selected microRNAs and their association with glucose metabolism in young women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances, such as insulin resistance and prediabetes, and the risk for their occurrence is especially increased in hyperandrogenic (HA) phenotypes of PCOS. Circulating microRNAs (miRNAs) may be involved in PCOS pathogenesis and regulation of metabolic processes. The aim of the study was to assess expression levels of selected circulating miRNAs in women with PCOS and to investigate the relationship of these miRNAs with glucose metabolism. The study included 95 patients with HA‑PCOS and 76 healthy women similar to the study group in age and body mass index. Measurements of sex hormone concentrations, oral glucose tolerance test (OGTT), and transvaginal ultrasonography were performed. Serum levels of selected miRNAs (miR‑27a, miR‑34a, miR‑106b, miR‑193b, miR‑181a, miR‑181b, and miR‑320) were assessed with real‑time polymerase chain reaction, and their association with PCOS and glucose metabolism parameters was studied. Serum levels of all studied miRNAs, except for miR‑34a, differed between the patients with HA‑PCOS and healthy women (all P <0.05). In HA‑PCOS, miR‑27a and miR‑320 levels correlated with fasting glucose (R = 0.33; P = 0.001 and R = -0.35; P <0.001, respectively) and insulin concentrations (R = 0.26; P = 0.01 and R = -0.23; P = 0.03, respectively). Additionally, the level of miR‑27a correlated with mean glucose concentration during OGTT (R = 0.26; P = 0.01). No such correlations were observed in the healthy women. In linear regression analyses, both miR‑27a and miR‑320 were associated with fasting glucose concentrations after adjustment for potentially confounding factors in the HA‑PCOS group only. The expression profile of circulating miRNAs is altered in patients with HA‑PCOS. Circulating miR‑27a and miR‑320 could serve as potential biomarkers of glucose metabolism disturbances in PCOS.

Hypoglycemic effects of propolis extract on polycystic ovarian syndrome in Wistar rats

Background: Polycystic ovarian syndrome (PCOS) is an endocrinopathy that causes various metabolic syndromes, including insulin resistance in 20-40% of patients. The treatment of the condition is often carried out using metformin, but it has been reported to have different gastrointestinal side effects. Consequently, several studies have recommended the use of propolis as an alternative, which has proven effective in improving insulin resistance in diabetic-induced rats and causes fewer side effects. Objective: This study aimed to compare the effects of propolis and metformin in treating insulin resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) value. Materials and Methods: This study used post-test-only randomized control trial design and the sample population comprised 30 Wistar rats. The animals were divided into 5 groups: control (C), PCOS (PCO), PCOS with metformin (PCO+M), PCOS with propolis extract (PCO+P), and PCOS with metformin and propolis extract (PCO+MP). Subsequently, blood sampling, ovarian tissue sampling, and vaginal smearing were performed after 28 days of treatment. Results: PCO+P and PCO+M groups experienced a significant decrease in testosterone concentration and preantral follicle count compared to PCOS group but the anovulation cycle was similar. Fasting blood glucose concentration in PCO+MP group showed a significant decrease compared to others. However, fasting insulin concentration and HOMA-IR value in treatment groups did not show any reduction compared to PCOS group. Conclusion: Based on the results, propolis extract and metformin could not improve insulin resistance based on HOMA-IR value. However, propolis extract had better hypoglycaemic effects compared to metformin. The combination of both treatments had the potential to lower fasting glucose concentration.

Insulin's Function in Health and Disease

Insulin is a polypeptide hormone that is primarily released by cells in the pancreatic islets of Langerhans. The hormone may work in tandem with glucagon to control blood sugar levels; glucagon has catabolic properties while insulin has anabolic ones. Insulin controls blood glucose levels and causes the liver, muscles, and adipose tissue to store glucose, which causes total weight gain. Insulin plays a crucial role in the initiation and development of many chronic diseases because it modulates a variety of physiological processes. Other techniques are based on the exogenous infusion of glucose or insulin, or both, either under steady-state (the insulin suppression test) or under dynamic conditions (the insulin tolerance test, intravenous glucose-tolerance test with minimal model analysis, and constant infusion of glucose with model analysis). Homeostatic model assessment uses fasting plasma glucose and insulin concentrations to derive indices of insulin sensitivity and secretion from a mathematical model.

Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial.

A supervised intense aerobic exercise program improves the health of individuals with metabolic syndrome (MetS). However, it is unclear whether the timing of training within the 24h day would influence those health benefits. The present study aimed to determine the influence of morning vs. afternoon exercise on body composition, cardiometabolic health and components of MetS. One hundred thirty-nine individuals with MetS were block randomized into morning (AMEX; n=42) or afternoon (PMEX; n=59) exercise training groups, or a non-training control group (Control; n=38). Exercise training was comprised of 48supervised high-intensity interval sessions distributed over 16weeks. Body composition, cardiorespiratory fitness (assessed by ), maximal fat oxidation (FOmax ), blood pressure and blood metabolites were assessed before and after the intervention. Compared with the non-training Control, both exercise groups improved similarly body composition (-0.7% fat loss; P=0.002), waist circumference (-2.1 cm; P<0.001), diastolic blood pressure (-3.8mmHg; P=0.004) and (3.5mLkg-1 min-1 ; P<0.001) with no differences between training groups. AMEX, in comparison with PMEX, reduced systolic blood pressure (-4% vs. -1%; P=0.019), plasma fasting insulin concentration (-12% vs. -5%; P=0.001) and insulin resistance (-14% vs. -4%; P=0.006). Furthermore, MetS Zscore was further reduced in the AMEX compared to PMEX (-52% vs. -19%; P=0.021) after training. In summary, high-intensity aerobic exercise training in the morning in comparison to training in the afternoon is somewhat more efficient at reducing cardiometabolic risk factors (i.e. systolic blood pressure and insulin sensitivity). KEY POINTS: The effect of exercise time of day on health promotion is an area that has gained interest in recent years; however, large-scale, randomized-control studies are scarce. People with metabolic syndrome (MetS) are at risk of developing cardiometabolic diseases and reductions in this risk with exercise training can be precisely gauged using a compound score sensitive to subtle evolution in each MetS component (i.e. Z score). Supervised aerobic exercise for 16weeks (morning and afternoon), without dietary restriction, improved cardiorespiratory and metabolic fitness, body composition and mean arterial pressure compared to a non-exercise control group. However, training in the morning, without changes in exercise dose or intensity, reduced systolic blood pressure and insulin resistance further compared to when training in the afternoon. Thus, high-intensity aerobic exercise training in the morning is somewhat more efficient in improving the health of individuals with metabolic syndrome.

Modelling the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity in a cohort of Australian adults.

Dietary guidelines are increasingly promoting mostly plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons. It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. We modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55 % female) from the Childhood Determinants of Adult Health study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using FFQ: 2004–2006, 2009–2011 and 2017–2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017–2019 (aged 39–49 years) using homoeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 10·5 percentage points, 95 % CI (4·1, 17·4)). Adjustment for waist circumference attenuated this association by 61·7 %. Replacing red meat with either legumes, nuts/seeds or wholegrains was likewise associated with higher insulin sensitivity. Point estimates were similar but less precise when replacing processed meat with plant-based alternatives. Our modelling suggests that regularly replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity. Further, abdominal adiposity may be an important mediator in this relationship. Our findings support advice to prioritise plant-based sources of protein at the expense of red meat consumption.

Insulin resistance without coexisting hyperglycaemia is not independently associated with cardiorespiratory fitness or its components in women

Abstract Background Insulin resistance (IR) is a globally prevalent condition in which tissues’ response to insulin is diminished. Cardiorespiratory fitness (peak O2 uptake (VO2peak)) is determined by Fick’s equation (VO2 = cardiac output (CO) × arteriovenous O2 difference (Ca-vO2) = heart rate × stroke volume (SV) × Ca-vO2) and diffusion law (VO2 = diffusive O2 conductance (DO2) × constant k × venous O2 pressure (PvO2)). Several studies suggest an association between IR and decreased VO2peak, but the association has been questioned by analyses taking account of body size and composition, and potential mechanisms behind the association are unknown. Purpose To test a hypothesis that IR is not independently associated with VO2peak or its components. Methods Fifty of 144 women, who had participated in baseline experiments of three intervention studies, were included in this retrospective cross-sectional study; see Table 1 for subject characteristics. The inclusion criteria were age 18-40 years, body mass index 18.5-40 kg/m2, Caucasian origin, and available data on key measures. The exclusion criteria were diseases, medications, and other factors possibly affecting VO2peak. We measured haemoglobin, fasting glucose, and fasting insulin concentrations (blood), assessed IR (homeostasis model assessment (HOMA-IR)), and measured body size and composition (bioimpedance). The subjects performed an incremental cycling test to volitional fatigue; we measured ventilatory gas exchange (spiroergometry), arterial O2 saturation (oximetry), and SV and CO (impedance cardiography), and calculated Ca-vO2, DO2, and PvO2. We analysed VO2peak and its components as absolute (e.g. L/min) and ratiometrically scaled values (e.g. mL/min/kg), and when appropriate, also as allometrically scaled values (e.g. mL/min/kg^x, where 0 &amp;lt; x &amp;lt; 1) after identifying optimal variable-specific exponents. Results VO2peak scaled to body mass (BM) as well as SVpeak and COpeak scaled to body surface area (BSA) were inversely associated with the body size variables they were scaled to (all P &amp;lt; 0.013). Contrariwise, this was not the case when we optimally scaled VO2peak to fat-free mass (FFM), SVpeak to FFM^0.55, COpeak to FFM^0.50, and DO2peak to FFM (all 0.066 &amp;lt; P &amp;lt; 0.977). HOMA-IR was inversely associated with VO2peak scaled to BM but not in a multivariate analysis, whereas HOMA-IR was not associated with VO2peak scaled to FFM (Table 2); we made alike observations with SVpeak and COpeak (data not shown). Further, VO2peak scaled to BM as well as SVpeak and COpeak scaled to BSA were or tended to be up to 15 % higher in a group with HOMA-IR&amp;lt;3.0 than in a group with HOMA-IR≥3.0, while other peak exercise data did not differ between the groups (Table 1). Conclusion Body size and composition significantly affect conclusions drawn regarding VO2peak and its components. Taking this into account, IR without coexisting hyperglycaemia is not independently associated with VO2peak or its components in women.Table 1Table 2