Normoglycemic Group Research Articles

Prediabetes is associated with increased cardiac events in patients with cancer who are prescribed anthracyclines.

Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.

Hyperglycemia as a prognostic factor for increased mortality in patients admitted in Pediatric ICU.

Objective: To study the prevalence and frequency of hyperglycemia in critically ill children. To juxtapose mortality rate in critically ill patients with hyperglycemia against those having normal blood glucose levels. Study Design: Descriptive Case Series. Setting: Pediatric Intensive Care Unit (PICU) of HITEC, IMS Taxila, Al-Ihsan Hospital Rawalpindi & Hameed Latif Teaching Hospital, Lahore. Period: March 2023 to October 2023. Methods: One hundred critically ill children admitted to PICU were included. Patients who had blood glucose levels more than 150mg/dl within 48 hours of admission were included in the hyperglycemic group (Group A).Patients with normal blood sugars were included in Group B. The normoglycemic and hyperglycemic groups were followed till 10 days to determine the mortality associated with hyperglycemia. Results: Mean age of the children was 6.7± 6.29 months. There were 72% male children and 28% female children. Mean blood glucose levels at baseline, after 24h hours, after 36 hours and after 48 hours were 194.91± 135.66mg/dl, 156.91±74.89mg/dl, 156.21 ±83.05mg/dl and 150.13±70.68mg/dl. Frequency of hyperglycemia was observed in 55% (n= 55). Mortality rate was 43% (n= 43/100). Furthermore, mortality rate was crucially inflated 63.6% (n= 35) in hyperglycemic victims than normoglycemic patients (p=<0.001). Conclusion: Frequency of high blood sugar along with mortality within 10 days of hospitalization in children with hyperglyceemia was found higher in patients admitted to Pediatric ICU.

Sustained Release of Salicylic Acid for Halting Peri-Implantitis Progression in Healthy and Hyperglycemic Systemic Conditions: A Gottingen Minipig Model.

To develop a peri-implantitis model in a Gottingen minipig and evaluate the effect of local application of salicylic acid poly(anhydride-ester) (SAPAE) on peri-implantitis progression in healthy, metabolic syndrome (MS), and type-2 diabetes mellitus (T2DM) subjects. Eighteen animals were allocated to three groups: (i) control, (ii) MS (diet for obesity induction), and (iii) T2DM (diet plus streptozotocin for T2DM induction). Maxillary and mandible premolars and first molar were extracted. After 3 months of healing, four implants per side were placed in both jaws of each animal. After 2 months, peri-implantitis was induced by plaque formation using silk ligatures. SAPAE polymer was mixed with mineral oil (3.75 mg/μL) and topically applied biweekly for up to 60 days to halt peri-implantitis progression. Periodontal probing was used to assess pocket depth over time, followed by histomorphologic analysis of harvested samples. The adopted protocol resulted in the onset of peri-implantitis, with healthy minipigs taking twice as long to reach the same level of probing depth relative to MS and T2DM subjects (∼3.0 mm), irrespective of jaw. In a qualitative analysis, SAPAE therapy revealed decreased levels of inflammation in the normoglycemic, MS, and T2DM groups. SAPAE application around implants significantly reduced the progression of peri-implantitis after ∼15 days of therapy, with ∼30% lower probing depth for all systemic conditions and similar rates of probing depth increase per week between the control and SAPAE groups. MS and T2DM conditions presented a faster progression of the peri-implant pocket depth. SAPAE treatment reduced peri-implantitis progression in healthy, MS, and T2DM groups.

Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Type 2 Diabetes: A Prospective Cohort Study.

Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. To prospectively investigate the association between serum 25-hydroxyvitamin D (25(OH)D) and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in the vitamin D receptor (VDR). This prospective study included 379 699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. During a median of 14.1 years of follow-up, 6315 participants with normoglycemia and 9085 patients with prediabetes developed T2D. Compared with individuals with 25(OH)D < 25 nmol/L, the multivariable-adjusted HRs (95% CIs) of incident T2D for those with 25(OH)D ≥ 75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia group and 0.64 (0.58, 0.70) among the prediabetes group. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (P interaction = .017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying the T allele of rs1544410. Triglyceride levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes, respectively. Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving the lipid profile, mainly triglycerides, accounted for part of the favorable associations.

Evaluation of a Lipid Profile in Normoglycemic and Pre-diabetic Saudi Office Employees in Makka Region: A Case-Control Study.

Diabetes mellitus (DM) poses a significant health challenge worldwide. The impact of a sedentary lifestyle in predicting and managing complications of diabetes represents an urgent need for health strategies. The objective of this study was to evaluate the lipid profile among normoglycemic and prediabetic Saudi office workers. The research was a case-control study carried out in Makkah al-Mukarramah (Kingdom of Saudi Arabia, KSA).Seventy-five office worker volunteers between the ages of 19 and 45 years were recruited for the study. The participants were divided into two groups: a control group of non-diabetic normal subjects (NGT) and prediabetic subjects with impaired fasting plasma glucose and/or impaired glucose tolerance (IGT), based on the American Diabetes Association recommendations. Measurements of glucose, hemoglobin A1C (HbA1C), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were performed using standard procedures and commercial kits. Statistical analysis was performed to compare the lipid profile in the two groups, and a P-value of <0.05 was considered statistically significant. A proportion (58.7%) of the office workers are prediabetics; prediabetic office workers had higher total cholesterol compared to the controlgroup (p < 0.05). Triglyceride levels were higher in office workers with prediabetes compared to the normoglycemic group (p < 0.05). LDL levels were elevated in the prediabetic office workerscompared to the control group (p < 0.05). Office employees with prediabetes exhibit elevated levels of cholesterol, triglycerides, and LDL. The disturbance in lipid profile may be linked to impaired glucose tolerance in individuals with a sedentary lifestyle, such as office workers.

Prediabetes and major adverse cardiac events after acute coronary syndrome: An overestimated concept.

Unlike diabetes, the effect of prediabetes on outcomes in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) is not much investigated. We investigated the association between fasting glycemic status and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with ACS undergoing PCI and had mid to long-term follow-up after coronary stenting. Registry-based retrospective cohort study included ACS patients who underwent PCI at the Tehran Heart Center from 2015 to 2021 with a median follow-up of 378 days. Patients were allocated into normoglycemic, prediabetic, and diabetic groups. The primary and secondary outcomes were MACCE and its components, respectively. Unadjusted and adjusted Cox models were used to evaluate the association between glycemic status and outcomes. Among 13 682 patients, 3151 (23%) were prediabetic, and 5834 (42.6%) were diabetic. MACCE risk was significantly higher for diabetic versus normoglycemic (adjusted hazard ratio [aHR]: 1.22, 95% confidence interval [CI]: 1.06-1.41), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 0.95, 95% CI: 0.78-1.10). All-cause mortality risk was significantly higher in diabetic versus normoglycemic (aHR: 1.42, 95% CI: 1.08-1.86), but nonsignificantly higher for prediabetic versus normoglycemic (aHR: 1.15, 95% CI: 0.84-1.59). Among other components of MACCE, only coronary artery bypass grafting was significantly higher in diabetic patients, and not prediabetic, compared with normoglycemic. Prediabetic ACS patients undergoing PCI, unlike diabetics, are not at increased risk of MACCE and all-cause mortality. While prediabetic patients could be regarded as having the same risk as nondiabetics, careful consideration to provide more intensive pre- and post-PCI care in diabetic patients is mandatory.

Cannabis sativa L. Fixed Oil and Its Nanoemulsion: Effect on Diabetes and Dyslipidemia Induced in Rats

Background: Diabetes Mellitus (DM) is a syndrome that interferes with energy metabolism and is caused by a decrease and dysfunction of insulin, leading to chronic hyperglycemia. DM associated with dyslipidemia is a severe health risk, increasing the chance of cardiovascular events, such as acute myocardial infarction and stroke. The Cannabis sativa L. fixed oil (CSO) is composed of unsaturated fatty acids and can be crucial in treating metabolic alterations. In addition, the nanoemulsion of C. sativa oil (NCS) has advantages in optimizing treatments. Objectives: This study aimed to evaluate the effects of treatments with CSO and its nanoemulsion (NCS) on induced diabetes and dyslipidemia in Wistar rats. Materials and methods: CSO’s physical-chemical and chromatographic characterization was performed, followed by the preparation of an NE containing 6% CSO. DM was induced in Wistar rats by intraperitoneal injection of streptozotocin (STZ) at a 55 mg/kg dose. Four days later, animals with blood glucose levels exceeding 300 mg/dL were considered diabetic. The rats were then divided into five groups ( n = 5) and treated orally. The groups included a normoglycemic control group (NOR), a diabetic control group, a group treated with metformin (100 mg/kg), a group treated with CSO (400 mg/kg), and a group treated with nanoemulsion (NCS 200 mg/kg). Subsequently, the pancreas’s clinical, biochemical, and histopathological parameters were evaluated. Results: In the chemical profile of CSO, it was observed the majority composition of palmitoleic (14.58%), oleic (12.50%), linoleic (42.40%), and linolenic (8.55%) acids. The results demonstrated that the induction of DM by STZ could reproduce the typical symptoms and clinical signs of DM. It was observed that treatments with CSO and NCS showed a significant improvement ( p &lt; .001) in polydipsia, polyuria, and loss of body mass, as well as a significant reduction ( p &lt; .001) of glucose levels in urine and blood and serum lipids. Histopathology of the pancreas revealed that treatment with CSO and NCS showed an increase in the number of cells in the islets of Langerhans and a decrease in regions devoid of cells, indicating possible cell regeneration. Moreover, insulin levels were significantly increased ( p &lt; .05) in the preferred groups. With dyslipidemia induced by Triton (Tyloxapol), it was observed that the treatment with CSO and NCS significantly decreased the levels of triglycerides ( p &lt; .05) and cholesterol ( p &lt; .001), as well as low-density lipoproteins (LDL) ( p &lt; .01). Conclusion: Treatment with CSO and NCS under the conditions of this study demonstrated an anti-diabetic effect and the ability to act in the reduction of triglyceride, cholesterol, and LDL levels. In this respect, treatments with CSO and NCS act in the control of DM, as well as in the prevention of cardiovascular diseases.

Glucose tolerance test with a single abnormal value as a predictor of type 2 diabetes mellitus: a multicenter retrospective study

Clinical implication of a single abnormal value (SAV) in the 100 g oral glucose tolerance test during pregnancy has not been established. We aimed to evaluate the risk of postpartum type 2 diabetes mellitus (T2DM) and investigate adverse pregnancy outcomes in women with SAV, using a retrospective database, from seven medical centers of Korea. Based on the Carpenter-Coustan criteria using two-step approach, pregnancy and postpartum outcomes were compared, among normoglycemic, SAV, and gestational diabetes mellitus (GDM) groups. Among 9353 women, 342 (3.66%) and 418(4.47%) women were included in SAV and GDM groups, respectively. SAV and GDM groups showed significantly higher rates of postpartum T2DM than normoglycemic group (7.60%, 14.83%, and 1.82%, respectively, p < 0.001). And SAV group showed significantly higher rates of pregnancy associated hypertension, preterm birth, and neonatal hypoglycemia and sepsis, compared to normoglycemic group (neonatal sepsis, p = 0.008; the others, p < 0.001). In multivariate analysis, postpartum T2DM was associated with SAV, GDM (with/without insulin), nulliparity, pre-pregnancy BMI, chronic hypertension, hyperlipidemia, and DM family history. A scoring model to predict postpartum T2DM within 5 years, achieved an area under the curve of 0.74. This study demonstrated that not only GDM, but also SAV is a significant risk factor for postpartum T2DM.

Protective effects of imeglimin on the development of atherosclerosis in ApoE KO mice treated with STZ

BackgroundImeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic β-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimin using atherosclerosis model ApoE KO mice treated with streptozotocin (STZ).MethodsApoE KO mice were divided into three groups: the first group was a normoglycemic group without injecting STZ (non-DM group, n = 10). In the second group, mice were injected with STZ and treated with 0.5% carboxymethyl cellulose (CMC) (control group, n = 12). In the third group, mice were injected with STZ and treated with imeglimin (200 mg/kg, twice daily oral gavage, n = 12). We observed the mice in the three groups from 10 to 18 weeks of age. Plaque formation in aortic arch and expression levels of various vascular factors in abdominal aorta were evaluated for each group.ResultsImeglimin showed favorable effects on the development of plaque formation in the aortic arch in STZ-induced hyperglycemic ApoE KO mice which was independent of glycemic and lipid control. Migration and proliferation of vascular smooth muscle cells and infiltration of macrophage were observed in atherosclerotic lesions in STZ-induced hyperglycemic ApoE KO mice, however, which were markedly reduced by imeglimin treatment. In addition, imeglimin reduced oxidative stress, inflammation and inflammasome in hyperglycemic ApoE KO mice. Expression levels of macrophage makers were also significantly reduced by imeglimin treatment.ConclusionsImeglimin exerts favorable effects on the development of plaque formation and progression of atherosclerosis.

The association of Healthy Eating Index and its components with levels of fasting blood sugar and lipid profile in normoglycemic and hyperglycemic individuals

PurposeThis study aims to assess the association of Healthy Eating Index (HEI) with levels of fasting blood sugar (FBS) and lipid profile in normoglycemic and elevated FBS patients.Design/methodology/approachThis case-control study was conducted on 144 participants, namely, 72 normoglycemic subjects (FBS < 100 mg/dl) and 72 high-glycemic patients (FBS ≥ 100 mg/dl) aged 20–60 years of age, who were selected from the nutrition and diet clinics in Tehran city. The dietary intake was collected by using a validated food frequency questionnaire to determine the HEI score.FindingsThe mean±SD age and body mass index of participants were 47.1 ± 12.7 years and 29.6 ± 6.0 kg/m2, respectively. The median (interquartile range) of HEI scores in the normoglycemic group and the high-glycemia group were 19.34 (15.24–24.31) and 16.53 (13.35–24.07), respectively. In the overall population, the findings of the multi-variable linear regression model indicated a positive association between the HEI score and high-density lipoprotein-cholesterol (HDL-C) (ß = 0.34; 95%CI: 0.05–0.64, P = 0.01). However, there is no significant association between HEI and HDL-C in normoglycemic (ß = 0.19; 95%CI: −0.31, 0.69, P = 0.45) and hyperglycemic subjects (ß = 0.28; 95%CI: −0.10–0.66, P = 0.15). Furthermore, the association of HEI with levels of FBS, triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-C) was not significant in any of the analyzed groups, including the total population, normoglycemic individuals and hyperglycemic subjects.Originality/valueThis study was the first study to assess the role of HEI and its components with levels of FBS and lipid profile in normoglycemic and hyperglycemic individuals in Iran. The findings suggested that higher adherence to HEI may be associated with an increase in the HDL-C level. However, HEI could not predict FBS, TGs and LDL-C levels in the adult population.

Impaired plasma glucose clearance is a key determinant of fasting hyperglycemia in people with obesity.

The objective of this study was to evaluate the relative importance of the basal rate of glucose appearance (Ra) in the circulation and the basal rate of plasma glucose clearance in determining fasting plasma glucose concentration in people with obesity and different fasting glycemic statuses. The authors evaluated basal glucose kinetics in 33 lean people with normal fasting glucose (<100 mg/dL; Lean < 100 group) and 206 people with obesity and normal fasting glucose (Ob < 100 group, n = 118), impaired fasting glucose (100-125 mg/dL; Ob 100-125 group, n = 66), or fasting glucose diagnostic of diabetes (≥126 mg/dL; Ob ≥ 126 group, n = 22). Although there was a large (up to three-fold) range in glucose Ra within each group, the ranges in glucose concentration in the Lean < 100, Ob < 100, and Ob 100-125 groups were small because of a close relationship between glucose Ra and clearance rate. However, the glucose clearance rate at any Ra value was lower in the hyperglycemic than the normoglycemic groups. In the Ob ≥ 126 group, plasma glucose concentration was primarily determined by glucose Ra, because glucose clearance was markedly attenuated. Fasting hyperglycemia in people with obesity represents a disruption of the precisely regulated integration of glucose production and clearance rates.

Trajectory of lung function in diabetic adults: A 16-year follow-up study of community-based prospective cohorts.

To investigate the difference in lung function according to diabetes status in a community-based prospective study. Individuals aged 40-69 years from two community-based cohorts were followed prospectively for 16 years. A spirometer was used to evaluate lung function at baseline, and lung function tests were carried out biennially thereafter. Multivariable linear regression analysis was performed for the cross-sectional and longitudinal analyses based on diabetes status. Among the 6483 subjects, 2114 (32.6%) had prediabetes and 671 (10.4%) had diabetes. The prediabetes and diabetes groups had lower baseline % predicted values of forced expiratory volume in 1 s (FEV1) (mean, -1.853; 95% confidence interval [CI] -2.715 to -0.990 for prediabetes and mean, -4.088; 95% CI -5.424 to -2.752 for diabetes) and forced vital capacity (FVC) (mean, -2.087; 95% CI -2.837 to -1.337 for prediabetes and mean, -4.622; 95% CI -5.784 to -3.460 for diabetes) compared to the normoglycemia group after adjusting for relevant covariates. The rate of decline in FEV1% predicted (mean, -0.227; 95% CI -0.366 to -0.089) and FVC % predicted (mean, -0.232; 95% CI -0.347 to -0.117) during follow-up were faster in the diabetes group than in the normoglycemia group. The diabetes group had a lower proportion of normal ventilation (ptrend = 0.048) and higher proportions of restrictive (ptrend = 0.001) and mixed (ptrend = 0.035) ventilatory disorders at the last follow-up. Diabetes is associated with a lower baseline lung function and a faster rate of deterioration.

Association of preclinical blood glucose with hospitalization rate and in-hospital mortality: A single-center retrospective cohort study.

Critical illness is often accompanied by elevated blood glucose, which generally correlates with increased morbidity and mortality. Prehospital blood glucose (PBG) level might be a useful and easy-to-perform tool for risk assessment in emergency medicine. This retrospective single-center cohort study was designed to analyze the association of prehospital glucose measurements with hospitalization rate and in-hospital mortality. Records of 970 patients admitted to a university hospital by an emergency physician were analyzed. Patients with a PBG ≥140mg/dL (G1, n=394, equal to 7.8mmol/L) were compared with patients with a PBG<140mg/dL (G2, n=576). Multivariable logistic regression models were used to correct for age, prediagnosed diabetes, and sex. Five hundred thirty-four patients (55%) were hospitalized. In comparison to normoglycemic patients, hyperglycemic patients were more likely to be hospitalized with an adjusted odds ratio (OR) of 1.48 (95% confidence interval [CI] 1.11-1.97), more likely to be admitted to the intensive care unit (ICU) with an adjusted OR of 1.74 (95% CI 1.31-2.31) and more likely to die in the hospital with an adjusted OR of 1.84 (95% CI 0.96-3.53). Hospitalized hyperglycemic patients had a median length of stay of 6.0 days (interquartile range [IQR] 8.0) compared to 3.0 days (IQR 6.0) in the normoglycemic group (P<0.001). In the subgroup analysis of cases without known diabetes, patients with PBG ≥140mg/dL were more likely to be hospitalized with an adjusted OR of 1.49 (95% CI 1.10-2.03) and more likely to be admitted to ICU/intermediate care with an adjusted OR of 1.80 (95% CI 1.32-2.45), compared to normoglycemic patients. Elevated PBG ≥140mg/dL was associated with a higher hospitalization risk, a longer length of stay, and a higher mortality risk and may therefore be included in risk assessment scores.

Waist circumference glucose, a novel and effective predictor of type 2 diabetes: a prospective cohort study.

Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures.

Hyperglycemia exacerbates cerebral ischemia/reperfusion injury by up-regulating autophagy through p53-Sesn2-AMPK pathway

Hyperglycemia exacerbates ischemic brain injury by up-regulating autophagy. However, the underlying mechanisms are unknown. This study aims to determine whether hyperglycemia activates autophagy through the p53-Sesn2-AMPK signaling pathway. Rats were subjected to 30-min middle cerebral artery occlusion (MCAO) with reperfusion for 1- and 3-day under normo- and hyperglycemic conditions; and HT22 cells were exposed to oxygen deprivation (OG) or oxygen–glucose deprivation and re-oxygenation (OGD/R) with high glucose. Autophagy inhibitors, 3-MA and ARI, were used both in vivo and in vitro. The results showed that, compared with the normoglycemia group (NG), hyperglycemia (HG) increased infarct volume and apoptosis in penumbra area, worsened neurological deficit, and augmented autophagy. after MCAO followed by 1-day reperfusion. Further, HG promoted the conversion of LC-3I to LC-3II, decreased p62, increased protein levels of aldose reductase, p53, P-p53ser15, Sesn2, AMPK and numbers of autophagosomes and autolysosomes, detected by transmission electron microscopy and mRFP-GFP-LC3 molecular probe, in the cerebral cortex after ischemia and reperfusion injury in animals or in cultured HT22 cells exposed to hypoxia with high glucose content. Finally, experiments with autophagy inhibitors 3-MA and aldose reductase inhibitor (ARI) revealed that while both inhibitors reduced the number of TUNEL positive neurons and reversed the effects of hyperglycemic ischemia on LC3 and p62, only ARI decreased the levels of p53, P-p53ser15. These results suggested that hyperglycemia might induce excessive autophagy to aggravate the brain injury resulted from I/R and that hyperglycemia might activate the p53-Sesn2-AMPK signaling pathway, in addition to the classical PI3K/AKT/mTOR autophagy pathway.

Adjuvant antimicrobial photodynamic therapy improves periodontal health and reduces inflammatory cytokines in patients with type 1 diabetes mellitus.

Antimicrobial photodynamic therapy (aPDT) is an adjuvant treatment to scaling and root planing (SRP) which improves periodontal health. It may be beneficial to patients with systemic diseases, such as type 1 diabetes mellitus. This randomized clinical trial evaluated the adjunctive effect of aPDT on the periodontal treatment of patients with type 1 diabetes (T1D). 38 patients were included in the study and divided into four groups: DSRP - T1D patients treated with SRP; CSRP - normoglycemic patients treated with SRP; DPDT - T1D patients treated with SRP + aPDT (methylene blue and red laser); CPDT - normoglycemic patients treated with SRP + aPDT. , Periodontal clinical parameters and inflammatory cytokines in crevicular fluid were recorded at baseline and then after 1, 3 and 6 months. The clinical endpoint for treatment was evaluated after 6 months. Adjuvant aPDT treatment resulted in reduction of probing depth after 3 months (0.38 mm - p<0.05) on T1D patients and in control group after 6 months (0.66 mm - p<0.05). Reduction of clinical attachment levels was similar for both treatments in control patients (p>0.05). There was a significant reduction of TNF-α in crevicular fluid in both groups treated with aPDT (p<0.05). The T1D (65%) and normoglycemic (72%) groups achieved the clinical endpoint after both treatments (p>0.05). Adjuvant aPDT provided additional benefits in improving periodontal clinical parameters and reducing inflammatory cytokines in both T1D and normoglycemic patients. However, normoglycemic patients showed greater clinical improvements compared to T1D patients following adjuvant aPDT treatment.

A low-inflammatory diet is associated with a lower incidence of diabetes: role of diabetes-related genetic risk

BackgroundWhether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes.MethodsAmong 142,271 diabetes-free UK Biobank participants (aged 39–72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7–6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression.ResultsDuring follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group.ConclusionsA low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.

Impaired Glucose Tolerance and Risk for Mild Cognitive Impairment and Dementia:Results from the SPRINT‐MIND Trial

AbstractBackgroundIn epidemiological studies, persons with a diagnosis of diabetes mellitus (DM), especially those with coexisting hypertension, have been shown to be at increased risk for dementia.[1‐3] However, the relationship between impaired glucose tolerance (IGT) and future risk of Mild Cognitive Impairment (MCI) and dementia is less clear, especially in persons without diagnosed DM . The SPRINT‐MIND trial (4) provides an opportunity to assess the relationship between baseline glucose level and risk for transition to mild cognitive impairment in the context of hypertension control.MethodRandomized clinical trial (n = 9,361) conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diagnosed diabetes or history of stroke. Baseline serum glucose obtained fasting and incidence of adjudicated MCI and probable dementia (PD) was calculated. Results were also stratified by age, baseline cardiovascular disease risk, and baseline systolic blood pressure.ResultAt baseline, 4398 participants (58%) had a serum glucose &amp;lt; 100 mg/dl and 3606 (42%) had a serum glucose &amp;gt;100. Overall, 389 (7.9%) of participants in the normoglycemic group and 250 (6.9%) of participants in the impaired glucose tolerance group developed MCI. For incident PD, 204 (4.1%) and 118 (3.3%) cases occurred in in persons with normal vs. impaired glucose tolerance. Incidence MCI or Dementia did not significantly differ when the results were stratified by baseline age or blood pressure.ConclusionIn persons with hypertension but without diagnosed diabetes, baseline impaired glucose tolerance does not confer elevated risk for MCI or dementia.

Association of serum uric acid levels with blood pressure and the incidence of hypertension in the middle-aged and elderly populations.

This study aimed to investigate the relationship between serum uric acid (SUA) levels and hypertension in the middle-aged and elderly populations. The cross-sectional analysis included 13 349 middle-aged and elderly general health checkup examinees without cardiovascular disease. The retrospective cohort analysis included 6659 normotensive participants (mean age: 64.6 years). Participants were divided into three groups based on their SBP/DBP levels: normal (<120/<80 mmHg), high normal (120-129/<80 mmHg), and elevated (130-139/80-89 mmHg), and were classified into three groups based on the results of 75 g oral glucose tolerance test: normoglycemia, prediabetes, and diabetes. SUA levels were significantly associated with SBP and DBP in this cross-sectional study. Over a mean 6.5-year follow-up period, 2038 participants developed hypertension. According to the SUA quartiles, the incidence of hypertension increased [26.1% in quartile (Q1) (≤4.1 mg/dl), 28.6% in Q2 (4.2-4.9 mg/dl), 32.6% in Q3 (5.0-5.8 mg/dl), 34.9% in Q4 (≥5.9 mg/dl); P for trend <0.001]. In multivariable analyses, SUA levels were positively associated with hypertension incidence only in the normal BP group [Q4 vs. Q1 odds ratio (OR): 1.64, 95% confidence intervals (CIs): 1.11-2.44; Q3 vs. Q1 OR: 1.69, 95% CI: 1.19-2.42] and in the normoglycemic group (Q4 vs. Q1 OR: 1.34, 95% CI: 1.02-1.76; Q3 vs. Q1 OR: 1.36, 95% CI: 1.07-1.74). In the middle-aged and elderly populations, normotensive or normoglycemic individuals with SUA levels at least 5 mg/dl may be potential targets for SUA management to prevent hypertension.

THU306 Association Of Prediabetes With Cardiovascular Outcomes Among Veterans With Obesity

Abstract Disclosure: J. Pendse: None. J. Mathew: None. S. Maidman: None. K. Mangalick: None. A. Ramachandran: None. E. Siddiqui: None. J.O. Aleman Diaz: None. Introduction: Prediabetes occurs frequently in obesity and is independently associated with increased atherosclerosis in nondiabetic patients. We sought to compare the effects of prediabetes on cardiovascular interventions along the glycemic control spectrum in obesity within the Veterans Health Administration (VHA), the largest US healthcare system. Methods: We conducted a systematic, retrospective review using the VHA Corporate Data Warehouse through the Veterans Administration Informatics and Computing Infrastructure database. We compared patients with obesity and prediabetes (preDM) to patients with obesity and normoglycemia (NG). Inclusion criteria included a body mass index (BMI) ≥ 30 kg/m2, Hemoglobin A1C (HbA1c) &amp;lt; 6.5% between 2000 and 2016. The intervention group included patients with preDM, defined by HbA1c between 5.7% to less than 6.5%, and the control group included patients with NG, defined as HbA1c&amp;lt; 5.7%. The primary endpoint was incidence of coronary revascularization, defined as a composite of percutaneous cardiac intervention (PCI) or coronary artery bypass graft (CABG). Secondary outcomes included PCI, CABG, diagnostic cardiac catheterizations, and mortality. Groups were compared using Pearson’s Chi-squared test or student t-tests when appropriate with alpha set to 0.05, and were assumed to have normal distribution. Results: A total of 137,487 subjects were included in the study, with 91,611 subjects with preDM and 45,876 subjects with NG. The average BMI among the preDM group was 33.8 kg/m2 ± 3.6 and the average BMI among the NG group was 33.4 kg/m2 ± 3.3 (p&amp;lt;0.001). Obesity/preDM subjects had a higher rate of coronary revascularization (6.3%, n=5,749) compared to obesity/NG subjects (3.1%, n=1,408) (p&amp;lt;0.001). From a total of 7,157 revascularized veterans, all-cause mortality rate was increased in preDM subjects (6.6%, n=851) compared to NG subjects (5.8%, n=221) (p&amp;lt;0.001). Obesity/preDM subjects had a higher rate of all-cause mortality (3.9%, n=3607) compared to obesity/NG subjects (2.8%, n= 1273). Also of note, obesity/preDM subjects had higher rates of diagnostic catheterization (11.9%, n=10,858), PCI (5.4%, n=4,913), stent (0.57%, n=528), CABG (1.2%, n=1087) compared with rates in obesity/NG subjects with diagnostic catheterization (7.1%, n=3272), PCI (2.6%, n=1183), stent (0.30%, n=138), and CABG (0.56%, n=258). Evaluating composite cardiovascular outcomes including PCI, stent, and CABG, obesity/preDM subjects had higher rates (6.3%, n=5749) compared with obesity/NG subjects (3.1%, n=1408). Conclusion: In this retrospective study, we have concluded that veterans diagnosed with obesity/preDM had higher rates of composite cardiovascular outcomes, including significantly higher rates of coronary revascularization procedures, overall mortality, and mortality following revascularization compared to veterans with obesity/NG. Presentation: Thursday, June 15, 2023