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1.
Cardiovasc Diabetol ; 23(1): 165, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730445

ABSTRACT

OBJECTIVE: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (ß-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.


Subject(s)
Biomarkers , Blood Glucose , C-Reactive Protein , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Disease Risk Factors , Hyperglycemia , Mendelian Randomization Analysis , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Biomarkers/blood , Hyperglycemia/blood , Hyperglycemia/epidemiology , Hyperglycemia/diagnosis , Hyperglycemia/mortality , Hyperglycemia/genetics , Risk Assessment , Blood Glucose/metabolism , Male , Denmark/epidemiology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/genetics , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Female , Middle Aged , Incidence , Up-Regulation , Myocardial Ischemia/blood , Myocardial Ischemia/genetics , Myocardial Ischemia/epidemiology , Myocardial Ischemia/diagnosis , Myocardial Ischemia/mortality , Aged , Prognosis , Inflammation Mediators/blood , Genetic Predisposition to Disease , Risk Factors
2.
J Diabetes ; 16(6): e13567, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769875

ABSTRACT

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.


Subject(s)
Hyperglycemia , Independent Living , Nutrition Surveys , Humans , Male , Female , Middle Aged , Independent Living/statistics & numerical data , Hyperglycemia/mortality , Hyperglycemia/blood , Hyperglycemia/epidemiology , Adult , Aged , Cause of Death , Risk Factors , Mortality/trends , Stress, Physiological , United States/epidemiology , Prognosis , Kaplan-Meier Estimate
3.
BMC Pregnancy Childbirth ; 24(1): 271, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609891

ABSTRACT

BACKGROUND: Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. METHODS: This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1-5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8-8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality - was analysed using multivariate logistic regression. RESULTS: The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71-1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60-1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27-0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18-0.57). DISCUSSION: The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.


Subject(s)
Diabetes, Gestational , Hyperglycemia , Pregnancy in Diabetics , Pregnancy , Infant, Newborn , Female , Humans , Glucose , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Hyperglycemia/epidemiology , Fasting
4.
Syst Rev ; 13(1): 116, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685068

ABSTRACT

BACKGROUND: Hyperglycemia in pregnancy (HIP) is a significant medical complication affecting pregnant women globally and is considered a public health burden due to the negative outcomes it can cause for both mother and infant. The aim of this systematic review and meta-analysis was to examine the prevalence, risk factors, and feto-maternal outcomes of HIP in Ethiopia. METHODS: To gather relevant information for this study, both published and unpublished studies were searched for in several major databases, including PubMed, Embase, HINARI, Web of Science direct, and Google Scholar, as well as other sources. The Joanna Briggs Institute (JBI) tool was used to evaluate the methodological quality of the findings from these studies. Data was then extracted and summarized using a template in Microsoft Excel software, and the extracted data was analyzed using Stata software version 16.0. If significant heterogeneity was found between studies, subgroup analyses were conducted to further examine the data. RESULT: Eighteen studies were included in this systematic review and meta-analysis, involving a total sample size of 50,816 pregnant women in Ethiopia. The prevalence of HIP among pregnant women varied considerably across the primary studies, ranging from 0.4 to 26.2%. The pooled prevalence of HIP among pregnant women in Ethiopia was found to be 6.9% (95% C 2.2-11.6). Pregnant women with a family history of diabetes had 2.5 times higher odds of developing HIP compared to those without a family history of diabetes (OR = 2.49; 95% CI = 2.02, 2.96). However, there was no significant association found between HIP and maternal obesity (OR 2.31, 95% CI = 0.85, 3.78) or previous history of abortion (OR 3.89; 95% CI 0.85, 6.94). The common fetal outcomes associated with HIP were admission to the intensive care unit (46.2; 95% CI 27.4, 65.1), macrosomia (27.3%; 95% CI 9.4%, 45.1%), and preterm birth (16.9; 95% CI 12.5, 21.3). Additionally, hypertensive disorders of pregnancy (28.0%; 95% CI 15.2, 40.8) and operative delivery (51.4%; 95% CI 35.9, 66.8) were more common among women with HIP in Ethiopia. CONCLUSION: Although there was some variation between studies, the meta-analysis revealed that approximately seven out of 100 pregnant women in Ethiopia had HIP. A family history of diabetes was found to be a significant predictor of HIP in Ethiopia. Additionally, HIP was associated with various serious adverse outcomes for both mothers and infants in Ethiopia. These findings highlight the need for national guidelines to ensure that pregnant women are uniformly screened for HIP.


Subject(s)
Hyperglycemia , Pregnancy Complications , Pregnancy Outcome , Humans , Pregnancy , Ethiopia/epidemiology , Female , Prevalence , Pregnancy Complications/epidemiology , Hyperglycemia/epidemiology , Risk Factors , Pregnancy Outcome/epidemiology , Diabetes, Gestational/epidemiology , Premature Birth/epidemiology
5.
RMD Open ; 10(2)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688692

ABSTRACT

OBJECTIVES: To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA). METHODS: We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia. RESULTS: 31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes. CONCLUSIONS: In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.


Subject(s)
Arthritis, Rheumatoid , Hyperglycemia , Prednisone , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/epidemiology , Prednisone/therapeutic use , Prednisone/adverse effects , Hyperglycemia/epidemiology , Hyperglycemia/etiology , Male , Female , Middle Aged , Diabetes Mellitus/epidemiology , Diabetes Mellitus/etiology , Severity of Illness Index , Aged , Blood Glucose , Adult , Antirheumatic Agents/therapeutic use , Antirheumatic Agents/adverse effects , Risk Factors
6.
BMJ Open ; 14(4): e080611, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688673

ABSTRACT

OBJECTIVE: We aimed to examine associations between educational level, serving as an indicator of socioeconomic position, and prevalence of WHO-established leading behavioural and biological risk factors for non-communicable diseases (NCDs), in middle-aged to older women and men. DESIGN: Population-based cross-sectional study. SETTING: All inhabitants of the municipality of Tromsø, Norway, aged ≥40 years, were invited to the seventh survey (2015-2016) of the Tromsø Study; an ongoing population-based cohort study. PARTICIPANTS: Of the 32 591 invited; 65% attended, and a total of 21 069 women (53%) and men aged 40-99 years were included in our study. OUTCOME MEASURES: We assessed associations between educational level and NCD behavioural and biological risk factors: daily smoking, physical inactivity (sedentary in leisure time), insufficient fruit/vegetable intake (<5 units/day), harmful alcohol use (>10 g/day in women, >20 g/day in men), hypertension, obesity, intermediate hyperglycaemia and hypercholesterolaemia. These were expressed as odds ratios (OR) per unit decrease in educational level, with 95% CIs, in women and men. RESULTS: In women (results were not significantly different in men), we observed statistically significant associations between lower educational levels and higher odds of daily smoking (OR 1.69; 95% CI 1.60 to 1.78), physical inactivity (OR 1.38; 95% CI 1.31 to 1.46), insufficient fruit/vegetable intake (OR 1.54, 95% CI 1.43 to 1.66), hypertension (OR 1.25; 95% CI 1.20 to 1.30), obesity (OR 1.23; 95% CI 1.18 to 1.29), intermediate hyperglycaemia (OR 1.12; 95% CI 1.06 to 1.19), and hypercholesterolaemia (OR 1.07; 95% CI 1.03 to 1.12), and lower odds of harmful alcohol use (OR 0.75; 95% CI 0.72 to 0.78). CONCLUSION: We found statistically significant educational gradients in women and men for all WHO-established leading NCD risk factors within a Nordic middle-aged to older general population. The prevalence of all risk factors increased at lower educational levels, except for harmful alcohol use, which increased at higher educational levels.


Subject(s)
Educational Status , Noncommunicable Diseases , Sedentary Behavior , Smoking , Humans , Female , Male , Middle Aged , Norway/epidemiology , Cross-Sectional Studies , Aged , Risk Factors , Adult , Prevalence , Aged, 80 and over , Smoking/epidemiology , Noncommunicable Diseases/epidemiology , Hypertension/epidemiology , Hypercholesterolemia/epidemiology , Obesity/epidemiology , Alcohol Drinking/epidemiology , Socioeconomic Factors , Hyperglycemia/epidemiology
7.
Front Endocrinol (Lausanne) ; 15: 1340435, 2024.
Article in English | MEDLINE | ID: mdl-38449856

ABSTRACT

Purpose: This study aimed to investigate the association between admission hyperglycemia and 30-day readmission after hip fracture surgery in geriatric patients. Methods: This retrospective study included 1253 geriatric hip fracture patients. Patients were categorized into normoglycemia(<6.10 mmol/L) and hyperglycemia groups(≥6.10 mmol/L) based on admission blood glucose. We performed multivariable logistic regression analyses and propensity score matching (PSM) to estimate adjusted odds ratios and 95% confidence intervals for 30-day readmission, controlling for potential confounding factors. An analysis of the dose-dependent association between admission blood glucose and the probability of 30-day readmission was performed. Additional subgroup analysis was conducted to examine the impact of other factors on the relationship between admission blood glucose and 30-day readmission. Results: Patients with hyperglycemia had higher 30-day readmission rates than normoglycemic patients before (19.1% vs 9.7%, p<0.001) and after PSM (18.1% vs 12.3%, p=0.035). Admission hyperglycemia was an independent predictor of increased 30-day readmission risk, with an adjusted odds ratio of 1.57 (95% CI 1.08-2.29, p=0.019) after multivariable regression and 1.57 (95% CI 1.03-2.39, p=0.036) after PSM. A dose-response relationship was observed between higher glucose levels and increased readmission risk. Conclusion: Admission hyperglycemia is an independent risk factor for 30-day readmission after hip fracture surgery in the elderly. Routine glucose testing upon admission and perioperative glycemic control may help reduce short-term readmissions in this vulnerable population.


Subject(s)
Hip Fractures , Hyperglycemia , Aged , Humans , Patient Readmission , Propensity Score , Blood Glucose , Retrospective Studies , Hip Fractures/surgery , Hyperglycemia/epidemiology
8.
Int J Cancer ; 154(11): 1940-1947, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38450737

ABSTRACT

Diabetes mellitus and cancer are both common health issues, but the correlation between these two diseases remains unclear. We investigated the association of cumulative exposure of diabetes mellitus as an indication of hyperglycemia in terms of disease duration on multiple cancer types. We hypothesized that the risk of cancer would increase over time after the onset of diabetes. The study population consisted of a population-based cohort of 398,708 people and it was constructed from the Finnish CARING project. The Diabetes group consisted of 185,258 individuals, and the non-diabetic reference group comprised 187,921 individuals. Over 4.1 million person-years were accumulated, and the median follow-up time was 10.55 years. In the diabetes group, 25,899 cancer cases were observed compared with 23,900 cancers in the non-diabetic group. We did not find a clear relationship between the duration of diabetes mellitus and most cancer types examined. However, for cancers of the pancreas, prostate gland, bronchus, and lungs, a temporal relationship was found. Furthermore, even within the cancer types where the relationship was detected, it did not change over time. These findings indicate that diabetes does not independently increase the risk of cancer. Instead, the development of diabetes may be attributed to shared risk factors with cancer, such as obesity and/or insulin resistance accompanied by hyperinsulinemia. Thus, it is likely that the clock for increased cancer risk starts ticking already before onset of diabetes and hyperglycemia.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes Mellitus , Hyperglycemia , Neoplasms , Male , Humans , Diabetes Mellitus/epidemiology , Neoplasms/etiology , Neoplasms/complications , Risk Factors , Hyperglycemia/complications , Hyperglycemia/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/complications
9.
Diabetes Res Clin Pract ; 210: 111607, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38453059

ABSTRACT

AIMS: To investigate the associations between weight change patterns and 5-year incident non-diabetic hyperglycaemia (NDH), and glycated haemoglobin (HbA1c) levels among individuals who had overweight or obesity. METHODS: This longitudinal cohort study (N = 435) pooled data from a weight management trial. Participants were adults with a body mass index of ≥28 kg/m2. They were categorised as "no weight loss", "maintainers", and "regainers" based on their weight at 3 months and 12 months after baseline. Multivariable logistic regression models and linear regressions were conducted to examine the associations. RESULTS: Between 1-year and 5-year follow-ups, 77 participants developed NDH. We found no statistically significant association between weight change patterns and incident NDH at 5 years. Among weight loss maintainers, mean HbA1c was -0.15% (95% confidence intervals (CI): -0.22, -0.10) lower after 1 year and -0.15% (95% CI: -0.23, -0.06) lower after 5 years compared to the no weight loss group. There was no difference between weight loss regainers and no weight loss group in HbA1c levels. CONCLUSIONS: Compared to those who did not lose weight, participants who maintained their weight loss had lower HbA1c levels after 1 year and 5 years, which highlights the importance of providing long-term support to prevent weight regain.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperglycemia , Adult , Humans , Overweight/epidemiology , Longitudinal Studies , Obesity/epidemiology , Weight Loss , Hyperglycemia/epidemiology
10.
Clin Pharmacol Ther ; 115(6): 1408-1417, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38425181

ABSTRACT

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide-use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self-reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene-environment interaction (GEI) tests on the significant (P < 2.5 × 10-9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10-3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10-4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9-mediated interaction having been previously reported. In conclusion, we used a two-stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide-associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.


Subject(s)
Biological Specimen Banks , Genome-Wide Association Study , Hyperglycemia , Hyperuricemia , Polymorphism, Single Nucleotide , Sodium Chloride Symporter Inhibitors , Humans , United Kingdom/epidemiology , Female , Hyperuricemia/genetics , Hyperuricemia/urine , Hyperuricemia/chemically induced , Male , Middle Aged , Hyperglycemia/genetics , Hyperglycemia/chemically induced , Hyperglycemia/urine , Hyperglycemia/epidemiology , Aged , Sodium Chloride Symporter Inhibitors/adverse effects , Uric Acid/urine , Uric Acid/blood , Quantitative Trait Loci , Gene-Environment Interaction , Hypertension/genetics , Hypertension/chemically induced , Blood Glucose/drug effects , Blood Glucose/metabolism , Potassium/urine , Potassium/blood , Sodium/urine , Adult , Biomarkers/urine , Biomarkers/blood , UK Biobank
11.
Diabetes Obes Metab ; 26(6): 2092-2101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38465689

ABSTRACT

AIMS: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. MATERIALS AND METHODS: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. RESULTS: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%-25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%-7%) and high triglyceride levels (2%-6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%-2%). CONCLUSIONS: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%-40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.


Subject(s)
C-Reactive Protein , Diabetes Mellitus, Type 2 , Inflammation , Interleukin-6 , Obesity, Abdominal , Tumor Necrosis Factor-alpha , Waist Circumference , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Female , Male , Middle Aged , Inflammation/blood , Inflammation/complications , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Tumor Necrosis Factor-alpha/blood , Interleukin-6/blood , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Hyperinsulinism/complications , Hyperinsulinism/epidemiology , Hyperinsulinism/blood , Aged , Adiposity , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Biomarkers/blood , Dyslipidemias/epidemiology , Dyslipidemias/blood , Hypertension/complications , Hypertension/epidemiology , Hyperglycemia/epidemiology , Adult
12.
Breast Cancer Res ; 26(1): 36, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38439079

ABSTRACT

BACKGROUND: Hyperglycemia is an on-target effect of PI3Kα inhibitors. Early identification and intervention of treatment-induced hyperglycemia is important for improving management of patients receiving a PI3Kα inhibitor like alpelisib. Here, we characterize incidence of grade 3/4 alpelisib-related hyperglycemia, along with time to event, management, and outcomes using a machine learning model. METHODS: Data for the risk model were pooled from patients receiving alpelisib ± fulvestrant in the open-label, phase 1 X2101 trial and the randomized, double-blind, phase 3 SOLAR-1 trial. The pooled population (n = 505) included patients with advanced solid tumors (X2101, n = 221) or HR+/HER2- advanced breast cancer (SOLAR-1, n = 284). External validation was performed using BYLieve trial patient data (n = 340). Hyperglycemia incidence and management were analyzed for SOLAR-1. RESULTS: A random forest model identified 5 baseline characteristics most associated with risk of developing grade 3/4 hyperglycemia (fasting plasma glucose, body mass index, HbA1c, monocytes, age). This model was used to derive a score to classify patients as high or low risk for developing grade 3/4 hyperglycemia. Applying the model to patients treated with alpelisib and fulvestrant in SOLAR-1 showed higher incidence of hyperglycemia (all grade and grade 3/4), increased use of antihyperglycemic medications, and more discontinuations due to hyperglycemia (16.7% vs. 2.6% of discontinuations) in the high- versus low-risk group. Among patients in SOLAR-1 (alpelisib + fulvestrant arm) with PIK3CA mutations, median progression-free survival was similar between the high- and low-risk groups (11.0 vs. 10.9 months). For external validation, the model was applied to the BYLieve trial, for which successful classification into high- and low-risk groups with shorter time to grade 3/4 hyperglycemia in the high-risk group was observed. CONCLUSIONS: A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes. REGISTRATION: ClinicalTrials.gov: NCT01219699 (registration date: October 13, 2010; retrospectively registered), ClinicalTrials.gov: NCT02437318 (registration date: May 7, 2015); ClinicalTrials.gov: NCT03056755 (registration date: February 17, 2017).


Subject(s)
Breast Neoplasms , Hyperglycemia , Thiazoles , Humans , Female , Breast Neoplasms/drug therapy , Fulvestrant/adverse effects , Hyperglycemia/chemically induced , Hyperglycemia/epidemiology , Risk Assessment
13.
Cardiovasc Diabetol ; 23(1): 59, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38336786

ABSTRACT

BACKGROUND: The stress hyperglycaemic ratio (SHR), a new marker that reflects the true hyperglycaemic state of patients with acute coronary syndrome (ACS), is strongly associated with adverse clinical outcomes in these patients. Studies on the relationship between the SHR and in-hospital cardiac arrest (IHCA) incidence are limited. This study elucidated the relationship between the SHR and incidence of IHCA in patients with ACS. METHODS: In total, 1,939 patients with ACS who underwent percutaneous coronary intervention (PCI) at the Affiliated Hospital of Zunyi Medical University were included. They were divided into three groups according to the SHR: group T1 (SHR ≤ 0.838, N = 646), group T2 (0.838< SHR ≤ 1.140, N = 646), and group T3 (SHR3 > 1.140, N = 647). The primary endpoint was IHCA incidence. RESULTS: The overall IHCA incidence was 4.1% (N = 80). After adjusting for covariates, SHR was significantly associated with IHCA incidence in patients with ACS who underwent PCI (odds ratio [OR] = 2.6800; 95% confidence interval [CI] = 1.6200-4.4300; p<0.001), and compared with the T1 group, the T3 group had an increased IHCA risk (OR = 2.1800; 95% CI = 1.2100-3.9300; p = 0.0090). In subgroup analyses, after adjusting for covariates, patients with ST-segment elevation myocardial infarction (STEMI) (OR = 3.0700; 95% CI = 1.4100-6.6600; p = 0.0050) and non-STEMI (NSTEMI) (OR = 2.9900; 95% CI = 1.1000-8.1100; p = 0.0310) were at an increased IHCA risk. After adjusting for covariates, IHCA risk was higher in patients with diabetes mellitus (DM) (OR = 2.5900; 95% CI = 1.4200-4.7300; p = 0.0020) and those without DM (non-DM) (OR = 3.3000; 95% CI = 1.2700-8.5800; p = 0.0140); patients with DM in the T3 group had an increased IHCA risk compared with those in the T1 group (OR = 2.4200; 95% CI = 1.0800-5.4300; p = 0.0320). The restriction cubic spline (RCS) analyses revealed a dose-response relationship between IHCA incidence and SHR, with an increased IHCA risk when SHR was higher than 1.773. Adding SHR to the baseline risk model improved the predictive value of IHCA in patients with ACS treated with PCI (net reclassification improvement [NRI]: 0.0734 [0.0058-0.1409], p = 0.0332; integrated discrimination improvement [IDI]: 0.0218 [0.0063-0.0374], p = 0.0060). CONCLUSIONS: In patients with ACS treated with PCI, the SHR was significantly associated with the incidence of IHCA. The SHR may be a useful predictor of the incidence of IHCA in patients with ACS. The addition of the SHR to the baseline risk model had an incremental effect on the predictive value of IHCA in patients with ACS treated with PCI.


Subject(s)
Acute Coronary Syndrome , Diabetes Mellitus , Heart Arrest , Hyperglycemia , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/therapy , Retrospective Studies , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Hyperglycemia/complications , Percutaneous Coronary Intervention/adverse effects , Incidence , Diabetes Mellitus/etiology , Non-ST Elevated Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/therapy , Heart Arrest/diagnosis , Heart Arrest/epidemiology , Heart Arrest/therapy , Treatment Outcome , Risk Factors
14.
Pan Afr Med J ; 47: 7, 2024.
Article in English | MEDLINE | ID: mdl-38371649

ABSTRACT

Introduction: the majority of studies in Ethiopia determine the prevalence of glycemic control employed by fasting blood sugar (FBS), which is impacted by a variety of factors. Hence, the purpose of this study was to assess the status of glycemic control using HbA1c and its correlates in patients with type 2 diabetes in Southwest Ethiopia. Methods: a cross-sectional study was employed among 124 T2 diabetes mellitus (DM) patients at Jimma Medical Center (JMC), Southwest Ethiopia. HbA1c and FBS were estimated using the Cobas 6000 analyzer. The body mass index (BMI) and waist-to-hip ratio were calculated as the standard formula. Data were analyzed by SPSS version 25. Logistic regression analysis was employed to identify independent risk factors associated with poor glycemic control of DM patients. Results: males comprised 63.7% (n=79) of the total respondents. The mean age of aOR: 2.21, 95% CI 1.13, 4.34; p = 0.01f participants was 51.84 ± 11.6 years; 60.5% (n=75) of T2 DM patients were in poor glycemic control (HbA1c ≥ 7%). In multivariate logistic regression analysis, BMI of ≥ 30, (aOR: 2.21, 95% CI 1.13, 4.34) increased waist-to-hip ratio (aOR: 1.63, 95% CI 0.82, 2.18), high systolic blood pressure (aOR: 1.52, 95% CI 1.11, 6.23), high FBS (aOR: 1.61, 95% CI 1.00, 4.12), and longer duration of DM (aOR: 1.23, 95% CI 0.87, 1.88) were associated with poor glycemic control. Conclusion: the level of poor glycemic control in the study population is high. Obesity and/or overweight, central obesity, systolic hypertension, and fasting blood sugar levels were all associated with poor glycemic control in T2 DM patients.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperglycemia , Male , Humans , Female , Diabetes Mellitus, Type 2/complications , Cross-Sectional Studies , Blood Glucose , Ethiopia/epidemiology , Glycated Hemoglobin , Glycemic Control , Hyperglycemia/epidemiology , Obesity/complications
15.
Diabetes Res Clin Pract ; 209: 111572, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38341041

ABSTRACT

OBJECTIVE: To describe changes in glucose-lowering drug (GLD) dispensing by frailty status for people with diabetes following admission for hypoglycaemia or hyperglycaemia. METHODS: This study included all people with probable type 2 diabetes in the state of Victoria, Australia, admitted to hospital for hypoglycaemia (n = 2,506 admissions) or hyperglycaemia (n = 1,693) between 1 July 2013 and 29 June 2017. Frailty was defined via the Hospital Frailty Risk Score (HFRS). We examined differences in dispensing of GLDs in the year before and after admission using linear regression models adjusted for age, sex, comorbidities, and socioeconomic status. RESULTS: Dispensing of GLDs decreased following hypoglycaemia admission. Decreased dispensing was strongly associated with frailty status, with a change in mean annual GLD dispensing count of -4.11 (-5.05, -3.17) for an HFRS of 15 vs. -0.99 (-1.47, -0.50) for an HFRS of 0. Changes were greatest for metformin and sulfonylureas. Following hyperglycaemia admission, the mean number of annual GLD dispensings increased, with a smaller increase with increasing frailty: 2.44 (1.32, 3.56) for an HFRS of 0 vs. 1.16 (0.18, 2.14) for an HFRS of 15. CONCLUSIONS: Frailty was associated with more conservative diabetes medication management following hypoglycaemia and hyperglycaemia admissions.


Subject(s)
Diabetes Mellitus, Type 2 , Frailty , Hyperglycemia , Hypoglycemia , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hyperglycemia/drug therapy , Hyperglycemia/epidemiology , Patient Discharge , Frailty/epidemiology , Aftercare , Hypoglycemia/drug therapy , Hypoglycemia/epidemiology , Retrospective Studies
16.
BMJ Paediatr Open ; 8(1)2024 02 10.
Article in English | MEDLINE | ID: mdl-38341196

ABSTRACT

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.


Subject(s)
Hyperglycemia , Insulin Resistance , Infant, Newborn , Humans , Infant , Proinsulin , Leptin , Ghrelin , Resistin , Prospective Studies , C-Peptide , Blood Glucose/metabolism , Insulin/metabolism , Infant, Very Low Birth Weight , Glucagon-Like Peptide 1 , Hyperglycemia/epidemiology , Insulin, Regular, Human
17.
J Diabetes Sci Technol ; 18(3): 556-561, 2024 May.
Article in English | MEDLINE | ID: mdl-38407141

ABSTRACT

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


Subject(s)
Hyperglycemia , Length of Stay , Humans , Retrospective Studies , Male , Length of Stay/statistics & numerical data , Female , Middle Aged , Hyperglycemia/blood , Hyperglycemia/epidemiology , Aged , Blood Glucose/analysis , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Postoperative Period , Glycated Hemoglobin/analysis , Postoperative Complications/epidemiology , Postoperative Complications/blood , Postoperative Complications/etiology , Cohort Studies
18.
Diabetes Res Clin Pract ; 208: 111116, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38266823

ABSTRACT

AIMS: Early postpartum glucose screening of women with hyperglycaemia in pregnancy (HIP) can identify women who have the highest risk of developing impaired glucose tolerance and T2DM. This study examines the association between demographics, events during pregnancy, socioeconomic status and postpartum T2DM screening. METHODS: Using the French National Health Data System, this cross-sectional study included all deliveries where the mother had HIP in France in 2015, (n = 76,862). The odds ratio (OR) for attending postpartum screening was calculated via multi-level logistic regression. RESULTS: T2DM screening uptake at six months postpartum was 42·9% [95 % Confidence Interval: 42·6-43·3]. Several characteristics were associated with lower uptake: living in the most deprived area(OR = 0·78[0·74-0·83]); being < 25 years-old (reference age group 25-29;≤17: 0.53 [0·31-0·90];18-24: 0.73[0·69-0·78]); smoking (0·65[0·62-0·68]); obesity (0·93[0·89-0·97]); caesarean delivery (0·95[0·92-0·99]). Factors associated with higher uptake included primiparity (1·30[1·26-1·34]); having followed the French recommendations for HIP screening (1·24[1·20-1·28]); insulin prescription (1·75[1·69-1·81]) and pre-eclampsia (1·30[1·19-1·42]). p < 0.01 is justified due to sample size. CONCLUSION: Improving identification of factors affecting postpartum T2DM screening uptake, such as demographics, socioeconomic context and events during pregnancy, may lead to development of target interventions to aide adherence to screening regime and thereby diagnosis of women with prediabetes or diabetes, for whom secondary and tertiary prevention is crucial.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Hyperglycemia , Pregnancy , Female , Humans , Adult , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Cross-Sectional Studies , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Glucose Tolerance Test , Postpartum Period
19.
Cardiovasc Diabetol ; 23(1): 29, 2024 01 13.
Article in English | MEDLINE | ID: mdl-38218835

ABSTRACT

BACKGROUND: The stress hyperglycemia ratio (SHR) has been demonstrated as an independent risk factor for acute kidney injury (AKI) in certain populations. However, this relationship in patients with congestive heart failure (CHF) remains unclear. Our study sought to elucidate the relationship between SHR and AKI in patients with CHF. METHODS: A total of 8268 patients with CHF were included in this study. We categorized SHR into distinct groups and evaluated its association with mortality through logistic or Cox regression analyses. Additionally, we applied the restricted cubic spline (RCS) analysis to explore the relationship between SHR as a continuous variable and the occurrence of AKI. The primary outcome of interest in this investigation was the incidence of AKI during hospitalization. RESULTS: Within this patient cohort, a total of 5,221 (63.1%) patients experienced AKI during their hospital stay. Upon adjusting for potential confounding variables, we identified a U-shaped correlation between SHR and the occurrence of AKI, with an inflection point at 0.98. When the SHR exceeded 0.98, for each standard deviation (SD) increase, the risk of AKI was augmented by 1.32-fold (odds ratio [OR]: 1.32, 95% CI: 1.22 to 1.46). Conversely, when SHR was below 0.98, each SD decrease was associated with a pronounced increase in the risk of AKI. CONCLUSION: Our study reveals a U-shaped relationship between SHR and AKI in patients with CHF. Notably, we identified an inflection point at an SHR value of 0.98, signifying a critical threshold for evaluating AKI in this population.


Subject(s)
Acute Kidney Injury , Heart Failure , Hyperglycemia , Humans , Retrospective Studies , Risk Factors , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Hyperglycemia/complications , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/complications
20.
Korean J Anesthesiol ; 77(2): 226-235, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38171594

ABSTRACT

BACKGROUND: Hyperglycemia has shown a negative association with cognitive dysfunction. We analyzed patients with high preoperative blood glucose level and hemoglobin A1c (HbA1c) level to determine the prevalence of postoperative delirium. METHODS: We reviewed a database of 23,532 patients with diabetes who underwent non-cardiac surgery. Acute hyperglycemia was defined as fasting blood glucose > 140 mg/dl or random glucose > 180 mg/dl within 24 h before surgery. Chronic hyperglycemia was defined as HbA1c level above 6.5% within three months before surgery. The incidence of delirium was compared according to the presence of acute and chronic hyperglycemia. RESULTS: Of the 23,532 diabetic patients, 21,585 had available preoperative blood glucose level within 24 h before surgery, and 18,452 patients reported levels indicating acute hyperglycemia. Of the 8,927 patients with available HbA1c level within three months before surgery, 5,522 had levels indicating chronic hyperglycemia. After adjustment with inverse probability weighting, acute hyperglycemia was related to higher incidence of delirium (hazard ratio: 1.33, 95% CI [1.10,1.62], P = 0.004 for delirium) compared with controls without acute hyperglycemia. On the other hand, chronic hyperglycemia did not correlate with postoperative delirium. CONCLUSIONS: Preoperative acute hyperglycemia was associated with postoperative delirium, whereas chronic hyperglycemia was not significantly associated with postoperative delirium. Irrespective of chronic hyperglycemia, acute glycemic control in surgical patients could be crucial for preventing postoperative delirium.


Subject(s)
Diabetes Mellitus , Emergence Delirium , Hyperglycemia , Humans , Blood Glucose , Glycated Hemoglobin , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Hyperglycemia/epidemiology
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