Impaired Glycemic Control Research Articles

Association of glycaemic control with intraocular pressure in a large general population: Results from the UK Biobank.

To evaluate the association of glycated haemoglobin (HbA1c) and serum glucose with intraocular pressure (IOP) in a large UK general population. Participants were selected from the UK Biobank, excluding those with eye conditions that may affect IOP. IOP was measured using an ocular response analyser. Goldmann-correlated IOP (IOPg) and corneal-compensated IOP (IOPcc) were outcomes of interest, and ocular hypertension was defined as left-eye IOPg or IOPcc > 21 mmHg. HbA1c and random (non-fasting) serum glucose were the exposures of interest. Multivariate restricted cubic spline models, as well as linear regression, were applied to explore the associations of interest. Among 68 806 participants (46.5% male), the mean age was 56.7 years. The mean (standard deviation) for IOPg was 15.7 (3.6) mmHg and 15.9 (3.6) mmHg for IOPcc. Occular hypertension was prevalent in 8055 participants (11.7%) and 4178 participants (6.1%) had diabetes. Those with diabetes had higher IOP and a higher prevalence of ocular hypertension. After adjustment for demographic and clinical variables, HbA1c was positively associated with IOP in participants with diabetes, but not in those without diabetes. For every 10-mmol/mol increase in HbA1c, IOPg increased by 0.20 mmHg (95% confidence interval [CI] 0.12, 0.28) and IOPcc by 0.15 mmHg (95% CI 0.07, 0.23); the odds of ocular hypertension was increased by 6% (95% CI 1.00, 1.13) in participants with diabetes. A borderline positive association between serum glucose and IOP was found only in participants without diabetes. Impaired glycaemic control was associated with elevated IOP and a possible risk of ocular hypertension among participants with diabetes but of normal ocular health.

Long-term diabetic hyperglycaemia modifies social behaviour in rats

Diabetes is a known risk factor for cognitive decline and mood disorders. However, the effects of long-term diabetic hyperglycaemia on the various dimensions of social behaviours, such as play or aggression, remains to be fully elucidated. In this study, we evaluated the social behaviour in a nicotinamide-streptozotocin rat model of long-term diabetic hyperglycaemia, in the absence of glucose-lowering treatments. Five months following induction of hyperglycaemia, we scored affiliative/exploratory or aggressive social interactions between pairs of unacquainted rats in a neutral arena. Our results demonstrate alterations in the behaviour of long-term diabetic rats faced with social novelties. Specifically, diabetic hyperglycaemic rats engaged in hyper-sociable and hyper-aggressive encounters. Interestingly, social interactivity was not associated with the degree of hyperglycaemia in affiliative/exploratory or in aggressive social interactions, in our long-term diabetic rat model. Altogether, our data suggest a lack of social appropriateness in long-term diabetic hyperglycaemic rats which is independent of the degree of hyperglycaemia. These findings support the importance of a tight glycaemic control in the management of diabetes at every stage of the disease and enlighten the importance of impaired glycaemic control as a novel metabolic player impacting the neural networks of social behaviours.

Effect of Vitamin D Supplementation on Glycemic Control in Newly Diagnosed Patients With Type 2 Diabetes Mellitus: A Randomized Controlled Trial.

Vitamin D deficiency is commonly associated with type 2 diabetes and it has been linked to impaired glycemic control in these patients. This study was done to determine if vitamin D supplementation improves glycemic parameters in type 2 diabetes. This randomized controlled trial was done in 140 newly diagnosed adult patients with type 2 diabetes. The participants were randomly divided into two groups where one group received vitamin D (60,000 International Units (IU) of oral vitamin D3 weekly for a duration of three months, followed by 1000 IU twice daily for another three months in vitamin D deficient patients; 1000 IU (25 mcg) twice daily for six months for subjects with sufficient vitamin D level) along with standard anti-diabetic drugs while the other group received standard anti-diabetic drugs only. The effect of vitamin D supplementation was assessed by measuring glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), fasting insulin, and insulin resistance as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at the baseline and after six months. Vitamin D deficiency was observed in 60% (n=84) of the subjects with the rest 40% (n=56) having sufficient serum vitamin D levels. The baseline mean HbA1c was 8.48 ± 1.46% and 8.21 ± 1.24% in the control and vitamin D group, respectively. After supplementing vitamin D for six months, no significant difference was observed between the two groups in terms of HbA1c (p= 0.263). Similarly, there was no significant change in other parameters like FBS, PPBS, fasting insulin, and insulin resistance (HOMA-IR). A subgroup analysis within the vitamin D group between the vitamin D sufficient and deficient patients also revealed no significant changes in the above parameters. Vitamin D supplementation, within the parameters of this study, did not yield a distinctive advantage in improving glycemic outcomes in individuals with type 2 diabetes.

The psychological burden associated with metabolic syndrome: Evidence from UK and US older adults.

We examined the psychological burden associated with metabolic syndrome (MetSyn). We used comparable longitudinal data of older adults (≥50years) from the UK (English Longitudinal Study of Aging) and the US (Health and Retirement Study). We defined MetSyn based on biomarker assessments (e.g., blood pressure, impaired glycemic control). Using regression models, we tested a range of individual psychological outcomes (e.g., depressive symptoms) associated with MetSyn. We also examined whether these psychological outcomes may explain or moderate the link between MetSyn and non-communicable diseases (NCDs). MetSyn was associated cross-sectionally with a range of psychological outcomes, including depression, anxiety, loneliness, hopelessness, cynical hostility, social strain, negative affect and decreased positive affect, social support and purpose in life. There was no convincing evidence that psychological factors interacted with or explained (mediated) the relationship between MetSyn and increased risk of developing NCD over 10-year follow-ups. MetSyn and the psychological burden outcomes examined may have independent effects on NCD risk.

Association Between the Triglyceride-Glucose Index and Serum Uric Acid to High-Density Lipoprotein (HDL) Cholesterol Ratio in Type 2 Diabetes Mellitus in Gabes City, Tunisia.

Background Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases (CVD). The triglyceride-glucoseindex (TyGi) is a novel biomarker for insulin resistance, strongly linked to CVD. Elevated serum uric acid levels and the uric acid to high-density lipoproteincholesterol ratio (UHR) are emerging as markers of metabolic syndrome and cardiovascular risk in T2DM. This study aimed to explore the association between the TyGiand UHR in T2DM patients. Objectives The aim of this study is to compare metabolic parameters in T2DM patients and assess the association between the TyGiand serum UHR. Methodology A cross-sectional case-control study was conducted at the University Hospital of Gabes, Gabes City, Tunisia with 50 T2DM patients and 50 gender-matched healthy controls. Inclusion criteria included adults aged 30-75 years with a confirmed diagnosis of T2DM on stable medication for at least three months. Exclusion criteria included other types of diabetes, significant liver or kidney disease, recent cardiovascular events, endocrine disorders, and substance abuse. Metabolic and biochemical parameters, including fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, lipid profile, and renal function, were measured. The TyGiand serum UHR were calculated and analyzed for correlations. Results T2DM patients exhibited significantly higher fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, TyGi, and serum UHR compared to controls, indicating impaired glycemic control and adverse lipid profiles. The UHR showed a positive correlation with a strong negative correlation with HDL and a positive correlation with uric acid levels. The linear regression analysis indicated a weak positive trend between the TyGi and serum UHR, although not statistically significant. Conclusion This study underscores the importance of the TyGiand serum UHRas biomarkers for evaluating metabolic and cardiovascular risk in T2DM. Further research is needed to explore their combined utility in clinical practice for early detection and management of cardiovascular complications in diabetic patients.

Effect of nano-curcumin supplementation on cardiometabolic risk factors, physical and psychological quality of life, and depression in patients with coronary slow flow phenomenon: a randomized double-blind clinical trial

BackgroundExtensive evidence has suggested the cardio-protective properties of the polyphenol curcumin. The aim of this study was to investigate the effects of a highly bioavailable curcumin supplement on cardiometabolic risk factors, health-related quality of life, and depression in patients with coronary slow flow phenomenon (CSFP).MethodsThis randomized double-blind placebo-controlled clinical trial was conducted in 42 patients with CSFP (age 35–70 years, 25 ≤ body mass index < 40 kg/m2). Patients received either 80 mg/day nano-curcumin or placebo for 12 weeks. Serum levels of visfatin, high-sensitivity C-reactive protein (hs-CRP), and glycemic indices were measured before and after the intervention. The short form 36-item quality of life (SF-36) and Beck’s Depression Inventory-II (BDI-II) questionnaires were assessed, as well.ResultsNo significant improvements were observed in circulating hs-CRP and visfatin following the intervention. A significant increase was observed in pre- to post-fasting blood glucose (− 0.9 ± 12.2 vs. 7.7 ± 12.4 mg/dl, p = 0.02) and hemoglobin A1C (− 0.1 ± 0.8 vs. 0.5 ± 0.8%, p = 0.04) levels, in the placebo compared with the intervention group. Physical (8.2 ± 8.1 vs. − 1.2 ± 6.5, p < 0.001) and mental (6.8 ± 11.8 vs. − 1.1 ± 10.4, p = 0.02) component summary scores were significantly improved in the nano-curcumin than the placebo group. Additionally, the number of patients with lower degrees of depression was significantly better in the intervention than the placebo group following the supplementation (p = 0.046).ConclusionCurcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with CSFP.Trial registrationIranian Registry of Clinical Trials (IRCT20131125015536N8), June 19, 2019.

Physical development of adolescents with type 1 diabetes mellitus and the impact of the war in Ukraine on its impairment

Purpose: To determine the characteristics of physical development (PD) of adolescents with type 1 diabetes mellitus (T1DM) and the impact of the war in Ukraine on its nature. Material and methods: The nature of physical development (PD) was assessed in adolescents with T1DM aged 14–18 years, examined before the start of the war on 24.02.2022 (main group, n = 114) and after 01.10.2022 (comparison group, n=76). The study was conducted in accordance with the principles of the Declaration of Helsinki and accepted by the Committee on Bioethics and Deontology. The examination of patients was carried out in accordance with the standards of medical care “Diabetes mellitus in children”, approved by Order of the Ministry of Health No. 413 of February 28, 2023 (Order of the Ministry of Health of Ukraine, 2023) and protocol for providing medical care to children in the specialty “pediatric endocrinology” (Order of the Ministry of Health of Ukraine, 2013). Results: It was proven that 29,1% of modern adolescents 14-17 years old, patients with T1DM, had a disharmonic PD, the nature of which depended on gender and the state of glycemic control. Girls were more likely to have impaired growth (21,0%) and overweight (12,8%), while boys were diagnosed with tall stature (8,9%) and underweight (8,9%). More often, PD disturbances were observed in the case of stable decompensation of carbohydrate metabolism with a decrease in the time spent in the target range and high levels of glycemic variability during the day. Among adolescents with T1DM during the period of hostilities in Ukraine, the number of adolescents with disharmonious PD increased (36,7%, P&lt;0,05), which may be due to a deterioration in glycemic control. In boys, an increase in the percentage of patients with underweight (20,0%, P&lt;0,05) and with short stature (4,0%, P&lt;0,05) was recorded, and in girls - with overweight (29,9 %, P&lt;0,05). Conclusions: confirms the negative impact of T1DM on RF, especially when socio-economic conditions worsen during armed conflicts. The relationship between the nature of risk factors, gender, the state of glycemic control and unfavorable living conditions during the war in Ukraine was determined.

Impaired glycemic control as a risk factor for reduced lung function in the Indian diabetic population

Diabetes mellitus (DM) is a metabolic syndrome associated with chronic hyperglycemia, which results in various acute and chronic complications. DM leads to a state of chronic low-grade inflammation, which can have adverse effects on pulmonary functions. There have been contradictory studies related to the relationship between defects in lung functions in diabetic individuals and their correlation with glycemic control and systemic inflammatory markers. The present study aims to compare pulmonary function in controlled and uncontrolled diabetes in the Indian population while exploring the link between inflammatory markers and lung functions in diabetic patients. This observational, case-control study was conducted in the Department of Biochemistry at Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar, Punjab, on 116 subjects suffering from DM in the age group of 30-65 years. 58 diabetic patients with poor glycemic control [glycated hemoglobin (HbA1c)&gt;7%] and 58 diabetic patients with good glycemic control served as controls (HbA1c≤7%). The duration of the study was two years. Blood samples of each patient were investigated for glycemic control, high-sensitivity C-reactive protein (hsCRP), and serum fibrinogen. Spirometry as a pulmonary function test was undertaken for all participants. The statistical analysis of good and poor glycemic control diabetics showed that the average duration of disease (in years) was 8±5 and 10.2±5.4, respectively. A significant positive correlation was found between inflammatory markers (hsCRP and fibrinogen) and HbA1c and fasting blood glucose. A substantial decline in forced vital capacity and normal values of forced expiratory volume in the first second was observed in poor glycemic control diabetics, depicting a restrictive pattern of lung disease. Lung damage is seen to be more prevalent in patients with a longer duration of disease and increased levels of inflammatory markers. Chronic inflammation due to DM can lead to fibrosis and destruction of lung tissue, resulting in the development of diabetic lung disease, which includes a decline in lung function, an increased risk of infection, and an increased risk of respiratory failure. Therefore, it is essential for individuals with DM to have regular pulmonary function tests and to manage their diabetes to minimize the impact on their lung health.

The Relation of Preoperative HbA1c Level With Intraoperative and Postoperative Complications in Type-2 Diabetic Patients: An Observational Study.

Background Perioperative dysglycemia increases morbidity and mortality, particularlyamong those with diabetes mellitus (DM), and elevated HbA1clevels,reflecting long-term blood glucose, are linked to poor healing and higher infection rates. This study investigates the link between preoperative HbA1c levels and perioperative outcomes in type-2 DM patients. Methodology This prospective observational study was conducted in India between January 2021 and April 2022. Sixty patients aged 18-60 with type-2 DM who underwent electivesurgery under general anesthesia (GA) were included; the American Society of Anesthesiologists class >III and patients with severe organ failures were excluded. Participants were divided into two groups: A (HbA1c ≤7.5%) and B (HbA1c >7.5%). Data on preoperative vitals, intraoperative hemodynamics, and postoperative complications were collected. SPSS v23 was used for data analysis; p-value <0.05 was considered significant. Results The mean age of the participants was 48.22 years; males comprised 58.3%. Group A had a higher proportion of oral hypoglycemic agents. Group B showed higher maximum mean blood pressure and intraoperative blood sugar levels at one hour. Postoperatively, Group B had higher glucose levels, more prevalent hyperglycemia, and higher preoperative and postoperative blood urea levels. No significant differences were found in postoperative outcomes like acute kidney injury (AKI), leukocytopenia, leucocytosis, fever, and intensive care admission. Surgical site infection (SSI) incidence was higher in group B, though not statistically significant. Group B had more extended hospital stays. Conclusion Preoperative HbA1c above 7.5% was associated with impaired perioperative glycemic control and higher dysglycemic episodes. Higher preoperative HbA1c was found to be linked to increased postoperative hyperglycemia, AKI, intensive care admissions, and more extended hospital stays, though not statistically significant. SSI incidence was higher, highlighting its importance over preoperative HbA1c.

Trajectories of BMI before and after diagnosis of type 2 diabetes in a real-world population.

Few studies have examined the clinical characteristics associated with changes in weight before and after diagnosis of type 2 diabetes. Using a large real-world cohort, we derived trajectories of BMI before and after diabetes diagnosis, and examined the clinical characteristics associated with these trajectories, including assessing the impact of pre-diagnosis weight change on post-diagnosis weight change. We performed an observational cohort study using electronic medical records from individuals in the Scottish Care Information Diabetes Collaboration database. Two trajectories were calculated, based on observed BMI measurements between 3 years and 6 months before diagnosis and between 1 and 5 years after diagnosis. In the post-diagnosis trajectory, each BMI measurement was time-dependently adjusted for the effects of diabetes medications and HbA1c change. A total of 2736 individuals were included in the study. There was a pattern of pre-diagnosis weight gain, with 1944 individuals (71%) gaining weight overall, and 875 (32%) gaining more than 0.5 kg/m2 per year. This was followed by a pattern of weight loss after diagnosis, with 1722 individuals (63%) losing weight. Younger age and greater social deprivation were associated with increased weight gain before diagnosis. Pre-diagnosis weight change was unrelated to post-diagnosis weight change, but post-diagnosis weight loss was associated with older age, female sex, higher BMI, higher HbA1c and weight gain during the peri-diagnosis period. When considering the peri-diagnostic period (defined as from 6 months before to 12 months after diagnosis), we identified 986 (36%) individuals who had a high HbA1c at diagnosis but who lost weight rapidly and were most aggressively treated at 1 year; this subgroup had the best glycaemic control at 5 years. Average weight increases before diagnosis and decreases after diagnosis; however, there were significant differences across the population in terms of weight changes. Younger individuals gained weight pre-diagnosis, but, in older individuals, type 2 diabetes is less associated with weight gain, consistent with other drivers for diabetes aetiology in older adults. We have identified a substantial group of individuals who have a rapid deterioration in glycaemic control, together with weight loss, around the time of diagnosis, and who subsequently stabilise, suggesting that a high HbA1c at diagnosis is not inevitably associated with a poor outcome and may be driven by reversible glucose toxicity.

Anesthesia considerations for pediatric metabolic and bariatric surgery

Childhood obesity is a rapidly growing global health issue, linked to significant lifelong morbidity and mortality. Its impact on various organ systems increases perioperative complications. Obesity treatment in children and adolescents involves lifestyle, dietary, and behavioral modifications, as well as pharmacologic interventions that targets hormonal, metabolic, and neurochemical abnormalities. Metabolic and bariatric surgery, proven safe and effective for adults with severe obesity (class 2 or higher), is now being recommended for adolescents. Key anesthetic considerations for these surgeries include preoperative optimization, advanced airway management, targeted ventilation strategies, and opioid-sparing analgesic regimens. Comprehensive presurgical evaluations must address co-morbid conditions such as hypertension, obstructive sleep apnea, asthma, and impaired glycemic control. Preoperative management should also consider the effects of antiobesity medications on gastric emptying and hemodynamic stability. Ventilation strategies should prevent atelectasis while avoiding barotrauma, and drug dosages must be adjusted for altered pharmacokinetics due to increased adipose tissue. Employing enhanced recovery after surgery protocols may reduce perioperative complications, shorten postsurgical stays, and improve outcomes.

Subarachnoid Hemorrhage as the First Manifestation of Pheochromocytoma with Remission of Hypertension and Diabetes Mellitus Postsurgery

Abstract Pheochromocytoma, a rare but life-threatening etiology of secondary hypertension, must be considered in patients with unexplained deterioration of glycemic control and new onset or worsening hypertension. We present the case of a 52-year-old female recently diagnosed with type 2 diabetes mellitus (T2DM) with a history of hypertension and subarachnoid hemorrhage (SAH), who reported intermittent headaches and palpitations at a routine checkup. Further evaluation confirmed elevated levels of urinary and plasma metanephrines, and imaging revealed a mass lesion in the right adrenal gland consistent with pheochromocytoma. The patient underwent laparoscopic right adrenalectomy with successful resolution of hypertension and diabetes. This case underscores considering pheochromocytoma as a differential in cases of hypertensive emergency or resistant hypertension, highlighting the potential for remission of hypertension and T2DM following tumor removal.

1600-P: Sunflower Oil HFD Feeding in Mice Leads to Gut Dysbiosis, Mild Steatohepatitis, and Impaired Glycemic Control

1600-P: Sunflower Oil HFD Feeding in Mice Leads to Gut Dysbiosis, Mild Steatohepatitis, and Impaired Glycemic Control

Diabetes-associated factors in hospitalized COVID-19 patients with concomitant type 2 diabetes mellitus: focus on mean in-hospital glycemic values

Aim of the study: to evaluate the significance of mean glycemic values during hospitalization as a potentially important diabetes-associated risk factor of unfavorable outcomes in inpatients with COVID-19 and type 2 diabetes mellitus (T2DM).Materials and methods. 139 patients with COVID-19 were observed in the hospital, 42 of them had concomitant type 2 diabetes mellitus (DM2). In patients with COVID-19 and type 2 diabetes, the relationship between mean glycemic values during hospitalization and adverse outcomes (death and/or transfer of the patient to the intensive care unit (ICU)) was assessed. The average number of tests to assess glycemia in the hospital was 38.4 ± 15.68 per patient.Results and discussion. According to correlation analysis data, an increase in mean in-hospital glycemia correlated with the severity of lung damage by computed tomography (R = 0.54, p = 0.002), the need for respiratory support by SMRT-CO score (R = 0.29, p = 0.070) and hypercoagulation by the international normalized ratio (R= –0.42, p=0.008). According to regression analysis, predictors of unfavorable outcomes included mean in-hospital glycemia (OR 1.4 [0.93; 2.12], p=0.073) and the percentage of tests with hypoglycemia in the hospital (OR 2.09 [0.89; 5 .40], p=0.016) as well as a history of diabetes (OR 5.5 [0.95, 31.60], p=0.029).Conclusion. Impaired glycemic control during the whole hospitalization period negatively affects disease severity and the risk of adverse outcomes in patients with COVID-19 and type 2 diabetes.

Glycated hemoglobin (HbA1c) is independently associated with the bioelectrical impedance phase angle in junior sumo wrestlers: A pilot study.

The study explores the relationship between phase angle (PhA), an indicator of cellular health, and metabolic health parameters among junior sumo wrestlers in Japan. Given the demanding lifestyle and high-energy diets of sumo wrestlers that predispose them to metabolic syndrome post-retirement, this study focuses on a younger cohort. The primary aim is to evaluate if PhA could serve as an early indicator of metabolic health issues within this unique demographic. A total of 14 sumo wrestlers aged 9-17 years were assessed to determine the relationship between PhA and various metabolic markers, including glycated hemoglobin (HbA1c), using a TANITA MC-780A-N body composition analyzer and standard blood tests. Bivariate regression analysis and Pearson's correlation revealed a negative relationship between PhA and HbA1c even after adjusting for age and weight (ß = -0.496, r2 = 0.776, r = -0.756, p = 0.004). The results indicate a significant negative relationship between PhA and HbA1c levels, suggesting that lower PhA values, which indicate poorer cellular integrity, are associated with higher HbA1c levels, signifying impaired glycemic control. These findings underscore the potential of PhA as a valuable biomarker for monitoring metabolic health in young sumo wrestlers, with implications for early intervention and management strategies.

Feasibility of Improving Glycemic Control via Heat Therapy in individuals at risk for Alzheimer’s Disease (FIGHT-AD): a pilot study

Impaired glycemic control increases the risk for type 2 diabetes and Alzheimer’s Disease (AD). Mechanisms such as impaired energy metabolism, cellular bioenergetic function, reduced intracellular protein homeostasis, and inflammation are all potential contributors to AD pathology. Heat therapy, via hot water immersion, has been shown to improve blood glucose regulation, insulin resistance, and inflammation. Given the potential contribution of these factors to brain health, heat therapy could offer immense clinical benefit to individuals at risk for AD. We performed a pilot study to test the feasibility of utilizing heat therapy in older individuals at risk for AD due to metabolic risk. The study intervention involved two pre-visits which included a cognitive function screen, sleep, diet, and physical activity questionnaires, as well as a glucose tolerance test and MRI scan. The intervention consisted of four weeks of heat therapy (3 visits/wk) for a total of 12 visits, followed by two post-intervention study visits identical to the pre-study visits. A total of 18 individuals (9 male, 9 female), average age 71.1 ± 3.9 y completed the intervention. Participants demonstrated metabolic risk based on average HbA1c values of 6.6 ± 0.67, Body Mass Index (BMI) of 29.1 ± 5.4, and 15 of the 18 participants were on hypertensive medications. Our cohort was highly diverse, with 33% underrepresented minority group representation. We had 96% participant adherence for the study (8 missed visits out of 216 total visits), and 1 study related Adverse Event (mild dizziness/nausea) that was mild. Overall, the research participants responded to a post-intervention survey saying they enjoyed participating in the study and it was not a burden on their schedules. In addition, we obtained preliminary data demonstrating a significant effect of the heat therapy intervention on body mass index, mean arterial pressure, and cerebral perfusion (p&lt;0.05), and a trend for improved self-reported sleep quality (Pittsburgh Sleep Quality Index; p=0.06). Future studies of longer duration are needed to provide a comprehensive understanding of the impact of heat therapy on glucose homeostasis and brain health. NIH P30 AG035982 (KU ADRC), pilot funds to PCG. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Enhanced interactions among gut mycobiomes with the deterioration of glycemic control

The gut mycobiome is closely linked to health and disease; however, its role in the progression of type 2 diabetes mellitus (T2DM) remains obscure. Here, a multi-omics approach was employed to explore the role of intestinal fungi in the deterioration of glycemic control. 350 participants without hypoglycemic therapies were invited for a standard oral glucose tolerance test to determine their statusof glycemic control. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping array, and plasma metabolites were measured with untargetedliquid chromatography mass spectrometry. The richness of fungi was higher, whereas its dissimilarity was markedly lower, in participants with T2DM. Moreover, the diversity and composition of fungi were closely associated with insulin sensitivity and pancreatic β-cell functions. With the exacerbation of glycemic control, the co-occurrence network among fungus taxa became increasingly complex, and the complexity of the interaction network was inversely associated with insulin sensitivity. Mendelian randomization analysis further demonstrated that the Archaeorhizomycetes class, Fusarium genus, and Neoascochyta genus were causally linked to impaired glucose metabolism. Furthermore, integrative analysis with metabolomics showed thatincreased 4-hydroxy-2-oxoglutaric acid, ketoleucine, lysophosphatidylcholine (20:3/0:0), and N-lactoyl-phenylalanine, but decreased lysophosphatidylcholine (O-18:2), functioned as key molecules linking the adverse effect of Fusarium genus on insulin sensitivity. Our study uncovers a strong association between disturbance in gut fungi and the progression of T2DM and highlights the potential of targeting the gut mycobiome for the management of T2DM. This study was supported by MOST and NSFC of China.

Glycemic Variability and the Thickness of Retinal Layers in Cystic Fibrosis Patients with and without Cystic Fibrosis Related Diabetes

Purpose Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. Methods During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Conclusion Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes.

The impact of handgrip strength and waist circumference on glycemic control: Prospective, observational study using outpatient clinical data in Japanese patients with type 2 diabetes mellitus.

Loss of muscle mass and the accumulation of visceral fat are known risk factors for the deterioration of glycemic control in type 2 diabetes mellitus. This study looked at the effects of such factors on glycemic control in Japanese patients with type 2 diabetes mellitus in the form of handgrip strength (HGS) and waist circumference (WC). In this prospective, observational study, 233 patients with type 2 diabetes mellitus and a HbA1c level of ≥7.0% were followed for around 1 year, during which time they were studied for an understanding of the association between handgrip strength, waist circumference, and glycemic control (HbA1c <7.0%). Hazard ratios (HRs) and 95% confidence intervals (CIs) for glycemic control improvement by Cox hazards models were analyzed for handgrip strength and waist circumference. Compared with the low tertile, patients in the middle and high tertiles of handgrip strength when adjustment was carried out for waist circumference were 2.117 (1.142-3.924) and 4.670 (2.526-8.632), respectively. The HRs of patients in the middle and high tertiles of WC when adjustment was made for HGS were 0.442 (0.269-0.725) and 0.339 (0.191-0.604), respectively. Within the low, middle, and high HGS tertiles, the HRs for WC were 0.863 (0.797-0.934), 0.940 (0.899-0.982), and 1.009 (0.984-1.035), respectively, although the HRs for HGS within each WC tertile remained significant. Handgrip strength and waist circumference demonstrated independent associations for glycemic control, but the effect of waist circumference appeared to be at least partially canceled out by increased handgrip strength. The data suggest that handgrip strength might help to mitigate the negative impact of waist circumference on glycemic control.

How safe are proprotein convertase subtilisinekexin type 9 inhibitors in diabetes?

To examine the safety of proprotein convertase subtilisinekexin type 9 (PCSK9) inhibitors in patients with diabetes, specifically focusing on their impact on glucose metabolism. Patients with diabetes often require intensified lipid-lowering therapy. PCSK9 inhibitors can reduce low-density lipoprotein cholesterol (LDL-C) concentrations by approximately 60%, and significantly reduce cardiovascular risk when added to statin therapy. Some studies have suggested an association between low LDL-C levels and an increased risk of new-onset diabetes, and genetics has almost consistently shown an increased glucose concentration and risk of diabetes. Most clinical trials have not demonstrated a deterioration in glycaemic control in patients with diabetes after the use of PCSK9 inhibitors, and they do not lead to other significant treatment-emergent adverse events. Although the majority of patients with diabetes are undergoing background statin therapy, which may mask potential adverse effects of PCSK9 inhibitors on glycaemic control, current data suggest that the benefits outweigh the risks for diabetic patients using PCSK9 inhibitors. Considering the different nature of genetic studies and of clinical trials, close monitoring of glucose parameters is necessary, especially in individuals with prediabetes.