BACKGROUND: Alkaloid- and polyphenol-rich white mulberry leaf and apple peel extracts have been shown to have potential glucose-lowering effects, benefitting the control of postprandial blood glucose levels. This study aimed to determine the effect of the combination of Malus domestica peel and Morus alba leaf extracts (GLUBLOCTM) on postprandial blood glucose and insulin-lowering effects in healthy adults after a carbohydrate-rich meal or sucrose drink intake.
METHODS: This study was designed as a randomized, crossover, single-blinded clinical trial. Out of 116 healthy participants, 85 subjects (aged 18-60 years) completed the day 1 and 5 crossover study. On day 1, subjects were supplemented with a placebo or GLUBLOCTM tablet 10 min before the carbohydrate-rich meal (300 g of tomato rice) or sucrose drink intake (75 g of sucrose dissolved in 300 mL water). On day 5, the treatments were crossed over, and the same diet was followed. Postprandial blood glucose and insulin levels were measured on days 1 and 5 (baseline 0, post-meal 30, 60, 90, and 120 min). Differences in iAUC, Cmax, and Tmax were determined between the placebo and GLUBLOCTM-treated cohorts.
RESULTS: Significant changes in total iAUC (0-120 min), Cmax, and Tmax of postprandial blood glucose and insulin levels were noticed upon GLUBLOCTM supplementation. The percentage reduction in the iAUC of blood glucose levels was 49.78% (iAUC0-60min) and 43.36% (iAUC0-120min), respectively, compared with the placebo in the sucrose drink intake study. Similarly, there was a 41.13% (iAUC0-60min) and 20.26% (iAUC0-120min) glucose-lowering effect compared with the placebo in the carbohydrate-rich meal intake study.
CONCLUSIONS: Premeal supplementation with GLUBLOCTM significantly reduced the postprandial surge in blood glucose and insulin levels after a carbohydrate-rich meal or sucrose drink intake over 120 min in healthy individuals. This study proves that GLUBLOCTM can manage steady postprandial blood glucose levels.

UNASSIGNED: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise\'s influence on adult diabetic rats\' memory and neuroplasticity.
UNASSIGNED: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (BDNF), calmodulin-dependent protein kinase (CAMKII), N-methyl-D-aspartate receptors (NMDAR), and cAMP-response element-binding protein (CREB) by western blotting and reverse transcription-polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study\'s conclusion, to assess Interleukin-1β levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1.
UNASSIGNED: Post-natal exercise improved spatial memory (p < 0.05) and glucose levels (p < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression (p < 0.05) in emerging adulthood for both training groups.
UNASSIGNED: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise\'s role in neuroplasticity memory enhancement and improved glucose level.

Detailed knowledge regarding the associations between intake of different types of seafood and meat and the risk of type 2 diabetes (T2D), and insight into possible mechanisms are warranted. In this study we aimed to evaluate the associations between intake of different types of seafood and meat and the subsequent risk of T2D using the Norwegian Mother, Father, and Child Cohort Study (MoBa), and furthermore, by using a mouse model to gain further insight into possible molecular mechanisms contributing to the associated metabolic changes. Women in MoBa who were free of pharmacologically treated diabetes at baseline (n = 60,777) were prospectively evaluated for incident T2D, identified on the basis of medication usages > 90 days after delivery, ascertained by the Norwegian Prescription Database. Dietary intake was obtained with a validated 255-item food frequency questionnaire which assessed habitual diet during the first 4-5 months of pregnancy. Metabolic phenotypes and plasma metabolome were investigated in female mice fed isocaloric diets with different types of seafood and meat mimicking the dietary intake in the human cohort. During maximum 10-year and mean (SD) 7.2 (1.6) years follow-up time, 681 (1.1%) women developed pharmacologically treated T2D. All statistical models identified a higher risk of T2D with increased shellfish intake, whereas no associations were observed for total seafood, fatty fish, total meat and red meat in the adjusted models. In mice, the shellfish-based western diet induced reduced glucose tolerance and insulin secretion compared to the diet based on lean fish, and we identified a number of metabolites elevated in plasma from shellfish-fed mice that correlated with glucose intolerance. Mice fed a western diet based on meat also exhibited reduced glucose tolerance in comparison to lean fish fed mice, whereas mice fed fatty fish, total seafood or red meat did not differ from lean fish fed mice. We observed a diet-specific metabolic signature in plasma demonstrating five distinct metabolite profiles in mice fed shellfish, fatty fish, total seafood/lean fish, a mixed diet and meat. In conclusion, these findings demonstrate that different types of seafood have different outcome on T2D risk. In women, intake of shellfish was associated with higher risk of T2D. In female mice, a shellfish enriched diet reduced glucose tolerance and altered the abundance of several distinct plasma metabolites correlating with glucose tolerance.

OBJECTIVE: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.
METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.
RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.
CONCLUSIONS: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

The existing literature does not address the question of the seasonal impact on pregnancy in Central-Eastern Europe; therefore, this study was designed to investigate the seasonal variation in gestational diabetes mellitus (GDM) based on a recent Polish sample. The data of 30,205 newborns from singleton pregnancies and their mothers, including the date and gestational age of birth, neonatal sex and weight, maternal age and parity, mode of delivery, ethnicity, and a detailed list of comorbidities (including GDM), were retrospectively analysed. The prevalence of GDM was significantly (p < 0.0001) lower in spring (14.71%) than in the other seasons (16.78%). A higher incidence of GDM was observed for mothers who underwent an oral glucose tolerance test from June to August compared to those who were tested from December to February (17.34% vs. 14.75%, p < 0.0001). Similarly, there were significant differences between seasons with higher and lower insolation. The regression analysis revealed that seasonal patterns were significantly associated with the prevalence of GDM. In conclusion, this large retrospective cohort study demonstrated seasonal changes in GDM risk. The observed seasonal patterns may equally refer to mothers of babies born at term and prematurely. Further research concerning GDM risk and other seasonal and gender associations is warranted.

(1) Background: Prior research in individuals with overweight/obesity and prediabetes or type 2 diabetes has shown that the ingestion of protein-rich food and non-starchy vegetables before concentrated carbohydrates (a carbohydrate-last food order) led to lower postprandial glucose excursions over 180 min, compared to eating the same foods in the reverse order. To expand upon this research, we sought to examine the feasibility and impact of carbohydrate-last food order behavioral intervention on glucose tolerance (GT), HbA1c, weight, and nutrient intake in adults with prediabetes in the real world over a 16-week span. (2) Methods: A total of 45 adults with overweight/obesity and prediabetes were randomized to receive 4-monthly standard nutritional counseling (C) or standard nutritional counseling plus carbohydrate-last food order counseling (FO) sessions (NCT# NCT03896360). (3) Results: The FO group decreased in body weight (-3.6 ± 5.7 lbs, p = 0.017), and trended toward lower HbA1c (-0.1 ± 0.2, p = 0.054). The C group weight trended lower (-2.6 ± 6.8 lbs, p = 0.102) without altering HbA1c (-0.03 ± 0.3, p = 0.605). GT was unchanged in both groups after 16 weeks. Changes in weight, HbA1c, and GT were similar between groups. Sensitivity analysis of pre-COVID participants showed significant weight loss in the FO group (-5.9 ± 5.3 lbs, p = 0.003) but not in C group (-1.0 ± 6.8 lbs, p = 0.608). After 16 weeks, the C group significantly reduced its daily intake of calories, fat, protein, and grains whereas the FO group increased its daily intake of vegetables and protein. There were 17 (94%) FO participants that reported high intervention adherence and 13 (72%) reported it was easy to eat protein/vegetables before carbohydrates. (4) Conclusions: A carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes that improves diet quality, notably increasing protein and vegetable intake.

Non-alcoholic fatty liver disease (NAFLD) is a very common liver disease associated with obesity, unhealthy diet, and lack of physical exercise. Short-term aerobic or resistance exercise has been shown to result in reduced liver fat in patients with NAFLD; however, the impact of the combination of these types of exercise has received less attention. This study investigated the effect of a short-term (7 days) concurrent exercise training program performed daily on liver steatosis indices, as well as the glycemic and lipidemic profile of overweight/obese sedentary volunteers. Twenty adult patients (age: 47.3 ± 12.3 yrs, body mass index: 32.4 ± 3.4 kg/m2) with NAFLD, detected by ultrasound and hematological indices, participated in the study. Pre- and post-exercise intervention assessment included body weight (BW), waist circumference (WC), hip/waist ratio (H/W), Homeostasis Model Assessment Insulin Resistance (HOMA-IR), blood lipids, and steatosis indices. Fatty Liver Index, Lipid Accumulation Index, WC, H/W, triglycerides, and total cholesterol were improved (p < 0.05) post-exercise, while no differences (p > 0.05) were observed in BW, HOMA-IR, HDL, LDL, Hepatic Steatosis Index, and Framingham Steatosis Index compared to pre-exercise values. It is concluded that a 7-day combined exercise program can have beneficial effects on hepatic steatosis and central adiposity indices, independently of weight loss, in patients with NAFLD.

The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment.
Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI).
Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia.
The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.

This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans.
A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis.
During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance.
A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

Pediatric obesity and cardiometabolic disease disproportionately impact minority communities. Sugar reduction is a promising prevention strategy with consistent cross-sectional associations of increased sugar consumption with unfavorable biomarkers of cardiometabolic disease. Few trials have tested the efficacy of pediatric sugar reduction interventions. Therefore, in a parallel-design trial, we randomized Latino youth with obesity (BMI ≥ 95th percentile) [n = 105; 14.8 years] to control (standard diet advice) or sugar reduction (clinical intervention with a goal of ≤10% of calories from free sugar) for 12-weeks. Outcomes included changes in glucose tolerance and its determinants as assessed by a 2-h frequently sample oral glucose tolerance test, fasting serum lipid profile (total cholesterol, HDL, LDL, triglycerides, cholesterol:HDL), and inflammatory markers (CRP, IL-6, TNF-α). Free sugar intake decreased in the intervention group compared to the control group [11.5% to 7.3% vs. 13.9% to 10.7% (% Energy), respectively, p = 0.02], but there were no effects on any outcome of interest (pall > 0.07). However, an exploratory analysis revealed that sugar reduction, independent of randomization, was associated with an improved Oral-disposition index (p < 0.001), triglycerides (p = 0.049), and TNF-α (p = 0.02). Dietary sugar reduction may have the potential to reduce chronic disease risks through improvements in beta-cell function, serum triglycerides, and inflammatory markers in Latino adolescents with obesity.