Association between pathologic complete response and biochemical indicators after neoadjuvant therapy for HER2-positive breast cancer.

PURPOSE: This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). METHODS: Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. RESULTS: In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. CONCLUSIONS: Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells.

BACKGROUND: Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro. METHODS: We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague-Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of ß-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals. RESULTS: Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to ß-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups. CONCLUSION: Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs.

Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

Evidence-based screening, clinical care and health education recommendations for Alaska Native peoples with prediabetes living in southcentral Alaska: findings from the Alaska EARTH follow-up study.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Assessing the Postprandial Glycemic Response to Japonica Rice (Oryza sativa L. cv. Koshihikari) with a Small Amount of Lysolecithin and Canola Oil in Japanese Adult Men: a Double-blind, Placebo-controlled, Crossover Study.

A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity. Subsequently, blood samples were collected before and 30, 45, 60, 90, and 120 min after consuming test foods. There was no significant difference in blood glucose, insulin, and triglyceride levels between the groups. However, a stratified analysis of 11 subjects with body mass index (BMI) ≥ 22 revealed that blood glucose levels were significantly lower after 30 min in the treatment group than in the placebo group (p = 0.041). Through in vitro digestibility test, the rice sample of the treatment group was observed to release significantly less glucose within 20 min than that in the placebo group rice. These results suggest that the combination of a small amount of lysolecithin and canola oil modulated the increase in postprandial blood glucose levels induced by the intake of cooked japonica rice in adult men with BMI ≥ 22. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center, (UMIN000045744; registered on 15/10/2021).

Effect of glycotoxicity and lipotoxicity on carbohydrate antigen 19 - 9 in the patients with diabetes.

OBJECTIVES: In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 - 9 (CA 19 - 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 - 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 - 9 in hospitalized patients with diabetes was the focus of our research. METHOD: A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. RESULTS: We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c < 9% group, 2.5% in the control group. There was no significant difference in the HbA1c < 9% group and the control group. A significant correlation between serum CA19-9 and both HbA1c and total cholesterol was observed, yet no difference in CRP level was observed between subjects with normal CA19-9 level and subjects with abnormal CA19-9 level. However, a significant difference in fasting C-peptide levels was observed between the two groups, p = 0.039. CONCLUSION: The percentage of patients with diabetes exhibiting elevated CA19-9 level is 14% in the HbA1c ≥ 9% diabetic patients, much higher than expected. The underlying mechanism may be related to islet injury caused by glycotoxicity and lipotoxicity. STRENGTHS AND LIMITATIONS OF THE STUDY: We studied the rate of hospitalized diabetic patients with elevated CA 19 - 9 which were characterized with poorly controlled blood glucose. We found that the elevation of CA 19 - 9 was unexpectedly high in diabetic inpatients without development to cancer. The limitation of this study is that the underlying mechanism is not sufficiently studied.

Cardiovascular risk screening: a 10-year prediction cross-sectional study in a Nigerian agrarian community.

Introduction: cardiovascular disease (CVD) is a major public health issue with a high global death rate and a significant death contribution from low-and middle-income countries. Modifiable and non-modifiable risk factors assessment and screening are important in their effective prevention and control. This study was designed to screen and assess cardiovascular risk factors in an agrarian community in Nigeria and to predict their 10-year CVD risk. Methods: this was a cross-sectional study carried out in the Umueri community in Anambra State, Nigeria. Each participant responded to an epidemiologic survey using the World Health Organization (WHO) cardiovascular risk factors assessment tool with point-of-care screening procedures. The risk assessment for 10-year CV risk was conducted using region-specific WHO/ISH charts. Patients´ characteristics were analyzed and presented in frequencies and percentages. Results: the mean age, systolic blood pressure, fasting plasma glucose, and total cholesterol of the study population were 54 years ± 1.27, 132 mmHg ± 2.088, 130 mg/dl ± 4.608, and 215 mg/dl ± 10.355 respectively. However, 98 (48.8%) have never had their blood pressure checked. About a quarter of the population had a high predicted risk of developing CVD within 10 years. Conclusion: most of the assessed cardiovascular risk factors in the community are on average above the normal ranges and their probability risk of developing CVD within the next 10 years is high.

Frequency of diabetic remission, predictors of remission and survival in cats using a low-cost, moderate-intensity, home-monitoring protocol and twice-daily glargine.

OBJECTIVES: The aim of the present study was to retrospectively assess remission rates and survival in diabetic cats managed using a moderate-intensity, low-cost protocol of home blood glucose measurements and insulin adjustment by clients of a cat-only practice, and to determine if predictors of remission, relapse or survival could be identified. METHODS: The records of a cat-only practice were used to identify 174 cats with newly diagnosed diabetes managed using only pre-insulin home blood glucose measurements for insulin dose adjustments based on a protocol provided to clients aimed at maintaining pre-insulin blood glucose in the range of 6.5-11.9 mmol/l (117-214 mg/dl). Cats were excluded for the following reasons: insufficient follow-up in the records; a lack of owner compliance was recorded; they were receiving ongoing corticosteroids for the management of other conditions; they were euthanased at the time of diagnosis; or they were diagnosed with acromegaly or hyperadrenocorticism. RESULTS: Using only pre-insulin blood glucose measurements at home to adjust the insulin dose to maintain glucose in the range of 6.5-11.9 mmol/l, 47% of cats achieved remission, but 40% of those cats relapsed. A minority (16%) of cats were hospitalised for hypoglycaemia. The survival time was significantly longer in cats in remission and Burmese cats. CONCLUSIONS AND RELEVANCE: The cost and time burden of treating diabetic cats may cause some clients to choose euthanasia over treatment. While the highest rates of diabetic remission have been reported in studies of newly diagnosed cats treated with intensive long-acting insulin protocols and low carbohydrate diets, these protocols may not be suitable for all clients. Nearly 50% of cats with newly diagnosed diabetes achieved remission with this low-cost, moderate-intensity, insulin dosing protocol. As remission was significantly associated with survival time, discussing factors in treatment to optimise remission is important, but it is also important to offer clients a spectrum of options. No cats that started treatment in this study were euthanased because the owner did not wish to continue the diabetes treatment.

The association between triglyceride glucose-body Mass Index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common reproductive disorder that frequently affects fertility. The TyG-BMI (Triglyceride glucose-body mass) index is a newly explored parameter that may be linked to reproductive results in individuals with PCOS. Nevertheless, its connection with outcomes in In Vitro Fertilization (IVF) procedures remains uncertain. METHODS: This study included a total of 966 females who underwent IVF treatments for PCOS. At the baseline, the participants were categorized into four groups according to the quartiles of TyG-BMI measured prior to oocyte retrieval. Subsequently, the study compared the differences in clinical and laboratory outcomes among these four groups. RESULTS: Patients in higher TyG-BMI quartiles exhibited a decreased number of retrieved oocytes, 2PN embryos, and available/high-quality embryos (P < 0.05 for Q1-Q4). Additionally, the multivariable regression analysis revealed that individuals in the top quartile of TyG-BMI had a lower count of accessible embryos (ß = -0.224, P = 0.257) and a decreased number of high-quality embryos (ß = -0.352, P = 0.028) in comparison to those in the lowest quartile. Nevertheless, there were no notable variances detected in the rates of pregnancy or live births among these quartiles. Furthermore, a linear correlation was noted between the TyG-BMI index and the quantity of accessible embryos (P-non-linear = 0.6, P-overall < 0.001), along with high-quality embryos (P-nonlinear = 0.026, P-overall = 0.006). In contrast, there was no notable linear correlation found between the TyG-BMI index and the available embryo rate (P-nonlinear = 0.60, P-overall = 0.8). CONCLUSIONS: The results of this research emphasize the notable correlation between TyG-BMI and IVF results in females diagnosed with PCOS. The interplay of insulin resistance and disorders of lipid metabolism may indeed play a pivotal role in influencing the assisted reproductive outcomes of patients with PCOS. Considering these findings, TyG-BMI proves to be a valuable indicator for exploring this potential association.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 µM ~ 2.0 mM) with high sensitivity (1546.32 µA cm-2 mM-1), a rapid response time (5 s), an ultralow detection limit (0.094 µM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay.

Short, frequent, light-intensity walking activity improves postprandial vascular-inflammatory biomarkers in people with type 1 diabetes: The SIT-LESS randomized controlled trial.

AIM: To examine the effect of interrupting prolonged sitting with short, frequent, light-intensity activity on postprandial cardiovascular markers in people with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized crossover trial, 32 adults with T1D (mean ± SD age 28 ± 5 years, glycated haemoglobin 67.9 ± 12.6 mmol/mol, 17 women) completed two 7-h laboratory visits separated by >7 days. Participants either remained seated for 7 h (SIT) or interrupted sitting with 3-min bouts of self-paced walking at 30-min intervals commencing 1 h after each meal (SIT-LESS). Physical activity, insulin regimen, experimental start times, and meal consumption were standardized during each arm. Plasma levels of interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, plasminogen activator inhibitor (PAI)-1 and fibrinogen were sampled at baseline, 3.5 and 7 h, and assessed for within- and between-group effects using a repeated measures ANOVA. The estimated glucose disposal rate was used to determine the insulin resistance status. RESULTS: Vascular-inflammatory parameters were comparable between SIT and SIT-LESS at baseline (p > .05). TNF-α, IL-1ß, PAI-1 and fibrinogen increased over time under SIT, whereas these rises were attenuated under SIT-LESS (p < .001). Specifically, over the 7 h under SIT, postprandial increases were detected in TNF-α, IL-1ß, PAI-1 and fibrinogen (+67%, +49%, +49% and +62%, respectively; p < .001 for all). Conversely, the SIT-LESS group showed no change in IL-1ß (-9%; p > .50), whereas reductions were observed in TNF-α, PAI-1 and fibrinogen (-22%, -42% and -44%, respectively; p < .001 for all). The intervention showed enhanced effects in insulin-resistant individuals with T1D. CONCLUSIONS: Interrupting prolonged sitting with light-intensity activity ameliorates postprandial increases in vascular-inflammatory markers in T1D. TRIAL REGISTRATION: The trial was prospectively registered (ISRCTN13641847).

Improvement of periodontal parameters following intensive diabetes care and supragingival dental prophylaxis in patients with type 2 diabetes: A prospective cohort study.

AIM: This study aimed to investigate the effects of diabetes care on periodontal inflammation. MATERIALS AND METHODS: This prospective cohort study included 51 Japanese patients with type 2 diabetes who underwent intensive diabetes care including educational hospitalization and regular outpatient treatment for 6 months. Dental prophylaxis without subgingival scaling was provided three times during the observational period. Associations between changes in periodontal parameters and glycaemic control levels were evaluated using multiple regression analysis. RESULTS: Overall, 33 participants (mean age: 58.7 ± 12.9) were followed up for 6 months. At baseline examination, 82% were diagnosed with Stage III or IV periodontitis. Haemoglobin A1c (HbA1c) level changed from 9.6 ± 1.8% at baseline to 7.4 ± 1.3% at 6 months. The ratio of probing pocket depth (PPD) ≥4 mm, bleeding on probing (BOP), full-mouth plaque control record (PCR), periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) also significantly improved. The reduction in PPD and PESA was significantly associated with changes in both HbA1c and fasting plasma glucose (FPG) levels, and the reduction in PISA was significantly associated with an improvement in FPG after adjusting for smoking, change in body mass index and full-mouth PCR. CONCLUSIONS: This is the first study to report a significant improvement in PPD and BOP after intensive diabetes care and dental prophylaxis without subgingival scaling. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000040218.

TyG-GGT is a Reliable Non-Invasive Predictor of Advanced Liver Fibrosis in Overweight or Obese Individuals.

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.

Semaglutide alleviates gut microbiota dysbiosis induced by a high-fat diet.

This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with high-fat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.

Continuous glucose monitoring and advanced glycation endproducts for prediction of clinical outcomes and development of cystic fibrosis-related diabetes in adults with CF.

Introductions: Cystic fibrosis-related diabetes (CFRD) is associated with pulmonary decline, compromised nutritional status, and earlier mortality. Onset is often insidious, so screening for early detection of glycemic abnormalities is important. Continuous glucose monitoring (CGM) has been validated in people with CF and has been shown to detect early glycemic variability otherwise missed on 2-hour oral glucose tolerance testing (OGTT). We previously reported that CGM measures of hyperglycemia and glycemic variability are superior to hemoglobin A1c (HbA1c) in distinguishing those with and without CFRD. However, little is known about the long-term predictive value of CGM measures of glycemia for both the development of CFRD and their effect on key clinical outcomes such as weight maintenance and pulmonary function. In addition, there have been no studies investigating advanced glycation endproducts (AGE) assessed by skin autofluorescence in people with CF. Methods: In this prospective observational study, CGM and HbA1c were measured at 2 to 3 time points 3 months apart in 77 adults with CF. Participants who did not have CFRD at the time of enrollment underwent OGTT at the baseline visit, and all participants had AGE readings at baseline. Follow up data including anthropometric measures, pulmonary function and CFRD status were collected by review of medical records 1- and 2-years after the baseline visits. We applied multivariable linear regression models correlating glycemic measures to change in key clinical outcomes (weight, BMI, FEV1) accounting for age, gender and elexacaftor/tezacaftor/ivacaftor (ETI) use. We also conducted logistic regression analyses comparing baseline glycemic data to development of CFRD during the 2-year follow up period. Results: Of the 77 participants, 25 had pre-existing CFRD at the time of enrollment, and six participants were diagnosed with CFRD by the OGTT performed at the baseline visit. When adjusting for age, gender, and ETI use, multiple CGM measures correlated with weight and BMI decline after one year but not after two years. CGM and HbA1c at baseline did not predict decline in FEV1 (p>0.05 for all). In the 46 participants without a diagnosis of CFRD at baseline, two participants were diagnosed with CFRD over the following two years, but CGM measures at baseline did not predict progression to CFRD. Baseline AGE values were higher in individuals with CFRD and correlated with multiple measures of dysglycemia (HbA1c, AG, SD, CV, TIR, % time >140, >180, >250) as well as weight. AGE values also correlated with FEV1 decline at year 1 and weight decline at year 1 and year 2. Conclusions: Several key CGM measures of hyperglycemia and glycemic variability were predictive of future decline in weight and BMI over one year in this population of adults with CF with and without CFRD. None of the baseline glycemic variables predicted progression to CFRD over 2 years. To our knowledge, this is the first report correlating AGE levels with key clinical and glycemic measures in CF. Limitations of these analyses include the small number of participants who developed CFRD (n=2) during the follow up period and the initiation of ETI by many participants, affecting their trajectory in weight and pulmonary function. These results provide additional data supporting the potential role for CGM in identifying clinically significant dysglycemia in CF. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD and to understand the implications of AGE measures in this patient population.

Triglyceride-glucose index demonstrates reasonable performance as a screening tool but exhibits limited diagnostic utility for insulin resistance: Data from the ELSA-Brasil cohort.

Insulin resistance (IR) is a key risk factor for chronic metabolic diseases, but its laboratory diagnosis is still costly; thus, the triglyceride-glucose (TyG) index has been proposed as a surrogate method. Our aim was to provide a detailed analysis of cutoffs and test the hypothesis that the TyG index would present reasonable performance parameters for IR screening. This is a cross-sectional study with baseline data from 12,367 eligible participants of both sexes (aged 35-74 years) from the Brazilian Longitudinal Study of Adult Health. TyG correlation and agreement with the Homeostasis Model Assessment for Insulin Resistance were analyzed. Positive and negative predictive values (PV+, PV-) and likelihood ratio (LR+, LR-) were calculated. A moderate positive correlation between TyG and Homeostasis Model Assessment for Insulin Resistance was observed (Pearson r = 0.419). The area under the receiver operating characteristic curve of TyG for IR diagnosis was 0.742 and the optimal cutoff was 4.665, reaching a kappa agreement value of 0.354. For this cutoff, a PV+ of 59.3% and PV- of 76.0%, as well as an LR+ of 2.07 and LR- of 0.45 were obtained. Alternatively, because high sensitivity is desired for screening tests, selecting a lower cutoff, such as 4.505, increases the PV- to 82.1%, despite decreasing the PV+ to 50.8%. We conclude that TyG has important performance limitations for detecting IR, but that it may still be reasonably useful to help screening for IR in adults because it can be calculated from low-cost routine blood tests.

Postoperative Length of Stay in Patients With Stress Hyperglycemia Compared to Patients With Diabetic Hyperglycemia: A Retrospective Cohort Study.

BACKGROUND: Postoperative hospital length of stay (LOS) is longer in patients with diabetes than in patients without diabetes. Stress hyperglycemia (SH) in patients without a history of diabetes has been associated with adverse postoperative outcomes. The effect of SH on postoperative LOS is uncertain. The aim of this study is to compare postoperative LOS in patients with SH to patients with diabetic hyperglycemia (DH) following noncardiac surgery. METHODS: We carried out a retrospective cohort study of inpatients with at least two glucose measurements ≥180 mg/dL. Two groups were compared. Patients with SH had no preoperative history of diabetes. Patients were considered to have DH if they had an established preoperative diagnosis of diabetes mellitus or a preoperative hemoglobin A1c (HbA1c) ≥6.5%. The primary outcome measure was hospital LOS. RESULTS: We included 270 patients with postoperative hyperglycemia-82 in the SH group and 188 in the DH group. In a linear regression analysis, hospital LOS was longer in the SH group than in the DH group (10.4 vs 7.3 days; P = .03). Within the SH group, we found no association between LOS and prompt treatment of hyperglycemia within 12 hours (P = .43), insulin dose per day (P = .89), or overall mean glucose (P = .13). CONCLUSIONS: Postoperative LOS was even longer in patients with SH than in patients with DH, representing a potential target for quality improvement efforts. We did not, however, find evidence that improved treatment of SH was associated with reduction in LOS.

Changes in inflammatory markers and efficacy analysis of continuous subcutaneous insulin infusion in senior patients with type 2 diabetes mellitus hospitalized with community-acquired pneumonia: a randomized controlled trial.

OBJECTIVE: The purpose of this study is to analyze the changes in inflammatory markers and efficacy in the treatment of senior patients with type 2 diabetes mellitus (T2DM) and community-acquired pneumonia with continuous subcutaneous insulin infusion (CSII). METHODS: A total of 105 senior patients with T2DM and community-acquired pneumonia, were randomly divided into two groups, viz., treatment group and control group-52 patients in the treatment group were treated with CSII, and 53 patients in the control group with multiple daily insulin injections (MDI). The changes in fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin, interleukin-6 indexes, and the improvement in clinical outcome between the two groups were compared on the 5th and the 10th day of treatment. RESULTS: In the treatment group, there were 52 patients with an average age of (73.7 ± 8.5) years, which included 28 males and 24 females. In the control group, there were 53 patients, with 27 males and 26 females, with an average age of (74.8 ± 8.8) years. On the 5th and the 10th day of the treatment, the fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin and interleukin-6 of the treatment group were better than that of the control group (P < 0.05). The use of CSII was associated with a higher probability of a prompt recovery (P < 0.05). CONCLUSION: The administration of CSII in the treatment of senior patients with T2DM and community-acquired pneumonia can effectively control fasting and postprandial blood glucose, significantly reduce the levels of inflammatory markers, and improve infection treatment efficacy.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

The Cost-Effectiveness of an Advanced Hybrid Closed-Loop System Compared to Standard Management of Type 1 Diabetes in a Singapore Setting.

Background: Despite advances in technology, glycemic outcomes in people with type 1 diabetes (T1D) remain suboptimal. The MiniMed 780G (MM780G) advanced hybrid closed-loop (AHCL) system is the latest technology for T1D management with established safety and efficacy. This study explores the cost-effectiveness of MM780G AHCL compared against multiple daily injections (MDI) plus intermittently scanned continuous glucose monitor (isCGM). Methods: A cost-utility analysis was conducted, simulating lifetime outcomes for 1000 T1D individuals, with baseline hemoglobin A1c of 8.4%, using the IQVIA Core Diabetes Model (CDM) v9.5. A Singapore health care payer perspective was taken with 2023 costs applied. Treatment effects were taken from the ADAPT study and treatment-related events from a combination of sources. T1D complication costs were derived from local literature, and health state utilities and disutilities from published literature. Scenario analyses and probabilistic sensitivity analyses (PSAs) explored uncertainty. Cost-effectiveness was assessed based on willingness-to-pay (WTP) thresholds set to Singapore Dollars (SGD) 45,000 (United States Dollars [USD] 33,087) per quality-adjusted life year (QALY) and Singapore's gross domestic product (GDP) per capita of SGD 114,165 (USD 83,941) per QALY. Results: A switch from MDI plus isCGM to MM780G resulted in expected gains in life-years (+0.78) and QALYs (+1.45). Cost savings through reduction in T1D complications (SGD 25,465; USD 18,723) partially offset the higher treatment costs in the AHCL arm (+SGD 74,538; +USD 54,805), resulting in an estimated incremental cost-effectiveness ratio of SGD 33,797 (USD 24,850) per QALY gained. Findings were robust, with PSA outputs indicating 81% and 99% probabilities of cost-effectiveness at the stated WTP thresholds. Conclusion: MM780G is a cost-effective option for people with T1D managed in a Singapore setting.