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BMC Endocrine Disorders Jul 2024The triglyceride-glucose index (TyG index) is a simple surrogate marker for Insulin Resistance (IR). However, the relationship between the TyG index and Metabolic...
BACKGROUND
The triglyceride-glucose index (TyG index) is a simple surrogate marker for Insulin Resistance (IR). However, the relationship between the TyG index and Metabolic Syndrome (MetS) remains unknown in the Northern Sri Lankan population.
METHODS
This was a descriptive, cross-sectional study of adults aged between 18 and 65 years living in Jaffna, Sri Lanka. This study aimed to verify the discriminative ability of the TyG index to identify MetS using the International Diabetes Federation (IDF-2006) criteria and to determine the gender-specific TyG index cut-off values for better prediction of MetS in Northern Sri Lankan adults. TyG index was calculated as Ln[Triglycerides (TG) (mg/dl) × Fasting plasma glucose (FPG) (mg/dl)/2].
RESULTS
A total of 540 individuals were included in this study, with a mean age of 42.18 (± 13.89) years for males and 43.80 (± 12.56) years for females. The mean value of the TyG index in the total study population was 8.54 (± 0.53). Individuals in the higher quartiles of the TyG index had a significantly increased risk of MetS compared with those in the lowest quartile (p < 0.01). TyG index showed a stronger association with MetS than the FPG and all the conventional lipid components and the unadjusted odds ratio was 5.47. The area under the curve (AUC) of ROC revealed values of 0.914 (95% confidence interval (CI): 0.884, 0.944) for females, 0.881 (95% CI: 0.830, 0.932) for males and 0.897 (95% CI: 0.870, 0.924) for the total study population. TyG index had a stronger discriminative ability to identify MetS as per IDF criteria in the study population with a cut-off value of 8.60. The mean level of the TyG index significantly increased with the increasing number of MetS components.
CONCLUSIONS
The mean value of the TyG index increased as the number of MetS components in the study population increased. Individuals with a higher TyG index had a significantly increased risk of having MetS compared with the lowest quartile of the TyG index. TyG index had a good discriminative ability to diagnose MetS as per IDF criteria among the northern Sri Lankan population.
Topics: Humans; Metabolic Syndrome; Male; Female; Adult; Middle Aged; Sri Lanka; Cross-Sectional Studies; Triglycerides; Blood Glucose; Biomarkers; Young Adult; Adolescent; Aged; Insulin Resistance; Prognosis
PubMed: 38951832
DOI: 10.1186/s12902-024-01632-2 -
Cardiovascular Diabetology Jun 2024Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose...
BACKGROUND
Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction.
METHODS
Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR).
RESULTS
Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results.
CONCLUSIONS
Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.
Topics: Mendelian Randomization Analysis; Humans; Genome-Wide Association Study; Adaptor Proteins, Signal Transducing; Risk Factors; Genetic Predisposition to Disease; Risk Assessment; Blood Glucose; Glucokinase; Biomarkers; Lipids; Phenotype; Carrier Proteins; Polymorphism, Single Nucleotide; Time Factors; Dyslipidemias; Fatty Liver
PubMed: 38951793
DOI: 10.1186/s12933-024-02321-z -
BMC Anesthesiology Jul 2024Postoperative hyperglycemia is associated with morbidity and mortality in non-diabetic surgical patients. However, there is limited information on the extent and factors...
BACKGROUND
Postoperative hyperglycemia is associated with morbidity and mortality in non-diabetic surgical patients. However, there is limited information on the extent and factors associated with postoperative hyperglycemia. This study assessed the magnitude and associated factors of postoperative hyperglycemia among non-diabetic adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.
METHODS
A facility-based cross-sectional study was conducted among 412 adult patients who underwent elective surgery at University of Gondar Comprehensive Specialized Hospital from April 14 to June 30, 2022 All consecutive postoperative non-diabetic elective surgical patients who were admitted to PACU during the data collection period and who fulfilled inclusion criteria were included in the study until the intended minimum sample size was achieved. And data were collected through interviews using a pretested semi-structured questionnaire. Postoperative hyperglycemia was defined as a blood glucose level of ≥ 140 mg/dl. Multivariable logistic regression was performed to identify the association between postoperative hyperglycemia and independent variables. Variables with a p-value less than 0.05 and a 95% confidence interval (CI) were considered statistically significant.
RESULTS
A total of 405 patients' data were evaluated with a response rate of 98.3%. The median (IQR) age was 40 (28-52) years. The prevalence of postoperative hyperglycemia was 34.1% (95% CI: 29.4-39.0). Factors significantly associated with postoperative hyperglycemia included being overweight (AOR = 5.45, 95% CI: 2.46-12.0), American Society of Anesthesiologists (ASA) classification II and III (AOR = 2.37, 95% CI: 1.17-4.79), postoperative low body temperature (AOR = 0.18, 95% CI: 0.069-0.48), blood loss ≥ 500 ml (AOR = 2.33, 95% CI: 1.27-4.27), long duration of surgery, mild pain (AOR = 5.17, 95% CI: 1.32-20.4), and moderate pain (AOR = 7.63, 95% CI: 1.811-32.20).
CONCLUSION AND RECOMMENDATION
One-third of the study participants had postoperative hyperglycemia. Weight, ASA classification, postoperative body temperature, duration of surgery, intraoperative blood loss, and postoperative pain were identified as a modifiable risk factors. Maintaining normal body temperature throughout the procedure, treating postoperative pain, and monitoring and controlling blood glucose level in patients at risk of hyperglycemia is crucial.
Topics: Humans; Ethiopia; Adult; Female; Male; Cross-Sectional Studies; Hyperglycemia; Middle Aged; Postoperative Complications; Elective Surgical Procedures; Risk Factors; Hospitals, University; Prevalence; Blood Glucose
PubMed: 38951764
DOI: 10.1186/s12871-024-02592-9 -
Scientific Reports Jul 2024Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure...
Life's Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2-6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.
Topics: Humans; C-Reactive Protein; Female; Middle Aged; Male; Cardiovascular Diseases; Cross-Sectional Studies; Risk Factors; Sweden; Inflammation; Body Mass Index; Exercise; Health Behavior; Blood Pressure; Blood Glucose
PubMed: 38951604
DOI: 10.1038/s41598-024-65977-3 -
Nutrition & Diabetes Jun 2024This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes...
BACKGROUND
This study aimed to assess whether the Haptoglobin (Hp) genotype influences the relationship between hemoglobin (Hb) levels and the development of gestational diabetes mellitus (GDM). Additionally, it sought to evaluate the interaction and joint association of Hb levels and Hp genotype with GDM risk.
METHODS
This retrospective study involved 358 women with GDM and 1324 women with normal glucose tolerance (NGT). Peripheral blood leukocytes were collected from 360 individuals at 14-16 weeks' gestation for Hp genotyping. GDM was diagnosed between 24-28 weeks' gestation. Interactive moderating effect, joint analysis, and mediation analysis were performed to evaluate the crosslink of Hb levels and Hp genotype with GDM risk.
RESULTS
Women who developed GDM had significantly higher Hb levels throughout pregnancy compared to those with NGT. Increase first-trimester Hb concentration was associated with a progressive rise in GDM incidence, glucose levels, glycosylated hemoglobin levels, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) values, cesarean delivery rates, and composite neonatal outcomes. Spline regression showed a significant linear association of GDM incidence with continuous first-trimester Hb level when the latter exceeded 122 g/L. Increased first-trimester Hb concentration was an independent risk factor for GDM development after adjusting for potential confounding factors in both the overall population and a matched case-control group. The Hp2-2 genotype was more prevalent among pregnant women with GDM when first-trimester Hb exceeded 122 g/L. Significant multiplicative and additive interactions were identified between Hb levels and Hp genotype for GDM risk, adjusted for age and pre-pregnancy BMI. The odds ratio (OR) for GDM development increased incrementally when stratified by Hb levels and Hp genotype. Moreover, first-trimester Hb level partially mediated the association between Hp genotype and GDM risk.
CONCLUSION
Increased first-trimester Hb levels were closely associated with the development of GDM and adverse pregnancy outcomes, with this association moderated by the Hp2-2 genotype.
Topics: Humans; Female; Pregnancy; Diabetes, Gestational; Haptoglobins; Retrospective Studies; Adult; Pregnancy Trimester, First; Genotype; Hemoglobins; China; Risk Factors; Asian People; Glycated Hemoglobin; Blood Glucose; Insulin Resistance; East Asian People
PubMed: 38951151
DOI: 10.1038/s41387-024-00309-y -
Zhonghua Nei Ke Za Zhi Jul 2024Abnormal glucose metabolism is closely related to stroke and has adverse effects on the occurrence, development, and prognosis of stroke. Ideal glycemic control is of...
Abnormal glucose metabolism is closely related to stroke and has adverse effects on the occurrence, development, and prognosis of stroke. Ideal glycemic control is of great significance in improving the prognosis of stroke. Some hypoglycemic drugs can reduce the risk of stroke occurrence and recurrence in patients with type 2 diabetes. Furthermore, such patients with stroke should strengthen their blood pressure and blood lipid control and use antiplatelet drugs reasonably. The expert consensus group finally established this consensus after discussions pertaining to evidence-based medicine and clinical practice, with the aim to provide a reference for clinical practice.
Topics: Humans; Diabetes Mellitus, Type 2; Stroke; Blood Glucose; Hypoglycemic Agents
PubMed: 38951088
DOI: 10.3760/cma.j.cn112138-20231201-00356 -
BMJ Open Jul 2024Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last...
INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.
INTRODUCTION
Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving β-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer β-cell protection. This study aims to assess the effect of influenza vaccination on preserving β-cell function in children and adolescents with recent-onset T1D.
METHODS AND ANALYSIS
The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual β-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D.
ETHICS AND DISSEMINATION
Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01.
Topics: Humans; Diabetes Mellitus, Type 1; Adolescent; Child; Influenza Vaccines; Double-Blind Method; Female; Male; Influenza, Human; Glycated Hemoglobin; C-Peptide; Randomized Controlled Trials as Topic; Blood Glucose; Insulin; Vaccination; Insulin-Secreting Cells
PubMed: 38950997
DOI: 10.1136/bmjopen-2024-084808 -
The Journal of Clinical Investigation Jun 2024Glucose plays a key role in shaping pancreatic β cell function. Thus, deciphering the mechanisms by which this nutrient stimulates β cells holds therapeutic promise...
Glucose plays a key role in shaping pancreatic β cell function. Thus, deciphering the mechanisms by which this nutrient stimulates β cells holds therapeutic promise for combating β cell failure in type 2 diabetes (T2D). β Cells respond to hyperglycemia in part by rewiring their mRNA metabolism, yet the mechanisms governing these changes remain poorly understood. Here, we identify a requirement for the RNA-binding protein PCBP2 in maintaining β cell function basally and during sustained hyperglycemic challenge. PCBP2 was induced in primary mouse islets incubated with elevated glucose and was required to adapt insulin secretion. Transcriptomic analysis of primary Pcbp2-deficient β cells revealed impacts on basal and glucose-regulated mRNAs encoding core components of the insulin secretory pathway. Accordingly, Pcbp2-deficient β cells exhibited defects in calcium flux, insulin granule ultrastructure and exocytosis, and the amplification pathway of insulin secretion. Further, PCBP2 was induced by glucose in primary human islets, was downregulated in islets from T2D donors, and impacted genes commonly altered in islets from donors with T2D and linked to single-nucleotide polymorphisms associated with T2D. Thus, these findings establish a paradigm for PCBP2 in governing basal and glucose-adaptive gene programs critical for shaping the functional state of β cells.
Topics: RNA-Binding Proteins; Animals; Insulin-Secreting Cells; Mice; Humans; Glucose; Diabetes Mellitus, Type 2; Insulin; Insulin Secretion; Mice, Knockout; Male; Adaptation, Physiological
PubMed: 38950317
DOI: 10.1172/JCI172436 -
Scandinavian Cardiovascular Journal :... Dec 2024Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress....
BACKGROUND
Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress. The impact of stress-induced hyperglycemia on the prognosis of ST-segment elevation myocardial infarction has been reported. However, the relationship between stress-induced hyperglycemia and the prognosis of AAAD patients remains uncertain.
METHODS
The clinical data of 456 patients with acute type A aortic dissection were retrospectively reviewed. Patients were divided into two groups based on their admission blood glucose. Cox model regression analysis was performed to assess the relationship between stress-induced hyperglycemia and the 30-day and 1-year mortality rates of these patients.
RESULTS
Among the 456 patients, 149 cases (32.7%) had AAAD combined with stress-induced hyperglycemia (SIH). The results of the multifactor regression analysis of the Cox model indicated that hyperglycemia (RR = 1.505, 95% CI: 1.046-2.165, = 0.028), aortic coarctation involving renal arteries (RR = 3.330, 95% CI: 2.237-4.957, < 0.001), aortic coarctation involving superior mesenteric arteries (RR = 1.611, 95% CI: 1.056-2.455, = 0.027), and aortic coarctation involving iliac arteries (RR = 2.034, 95% CI: 1.364-3.035, = 0.001) were independent influences on 1-year postoperative mortality in AAAD patients.
CONCLUSION
The current findings indicate that stress-induced hyperglycemia measured on admission is strongly associated with 1-year mortality in patients with AAAD. Furthermore, stress-induced hyperglycemia may be related to the severity of the condition in patients with AAAD.
Topics: Humans; Retrospective Studies; Aortic Dissection; Male; Female; Hyperglycemia; Middle Aged; Time Factors; Risk Factors; Aged; Blood Glucose; Aortic Aneurysm; Risk Assessment; Acute Disease; Biomarkers; Prognosis; Adult
PubMed: 38949610
DOI: 10.1080/14017431.2024.2373099 -
Frontiers in Endocrinology 2024Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their...
OBJECTIVES
Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats.
METHODS
Eight-week-old male Sprague-Dawley rats were fed either HFD or chow diet for 24 weeks. Additionally after 12 weeks, HFD-fed rats switched either to chow diet, voluntary intermittent running exercise, or both for another 12 weeks. BMAd morphology was assessed by perilipin-1 immunofluorescence staining in formalin-fixed paraffin-embedded tibial sections. Insulin-stimulated sternal and humeral BMGU were measured using [F]FDG-PET/CT. Tibial microarchitecture and mineral density were measured with microCT.
RESULTS
HFD rats had significantly higher whole-body fat percentage compared to the chow group (17% vs 13%, respectively; = 0.004) and larger median size of BMAds in the proximal tibia (815 µm vs 592 µm, respectively; = 0.03) but not in the distal tibia. Switch to chow diet combined with running exercise normalized whole-body fat percentage ( < 0.001) but not the BMAd size. At 32 weeks of age, there was no significant difference in insulin-stimulated BMGU between the study groups. However, BMGU was significantly higher in sternum compared to humerus ( < 0.001) and higher in 8-week-old compared to 32-week-old rats ( < 0.001). BMAd size in proximal tibia correlated positively with whole-body fat percentage (r = 0.48, = 0.005) and negatively with humeral BMGU (r = -0.63, = 0.02). HFD significantly reduced trabecular number ( < 0.001) compared to the chow group. Switch to chow diet reversed this as the trabecular number was significantly higher ( = 0.008) than in the HFD group.
CONCLUSION
In this study we showed that insulin-stimulated BMGU is age- and site-dependent. BMGU was not affected by the study interventions. HFD increased whole-body fat percentage and the size of BMAds in proximal tibia. Switching from HFD to a chow diet and running exercise improved glucose homeostasis and normalized the HFD-induced increase in body fat but not the hypertrophy of BMAds.
Topics: Animals; Male; Rats, Sprague-Dawley; Rats; Adiposity; Diet, High-Fat; Physical Conditioning, Animal; Bone Marrow; Glucose; Obesity; Adipocytes
PubMed: 38948514
DOI: 10.3389/fendo.2024.1422869