Prediabetes Research Articles

HPB SO74 - Autologous Islet Transplantation combined with Pancreatic resection in Adults and Children

Abstract Background After extended pancreatic resections there is a risk of developing difficult to manage diabetes. The current NHS commissioning criteria only allows autologous islet isolation and transplantation in adult patients having total pancreatectomy for chronic pancreatitis. We present our experience of pancreatic resection combined with autologous islet transplantation (AIT) in both adults and children. Method Patients were assessed for AIT electively or as an emergency if an extended resection was required for trauma. Patients with chronic pancreatitis were assessed for Total Pancreatectomy (TP) by a multi-disciplinary team which included gastroenterologists, diabetes physicians, pain specialists, surgeons and psychiatrists. A similar approach was used in children. Patients were evaluated pre-operatively with a MMT to assess any borderline diabetes. Results 22 (20 adults and 2 children, age range 9-64 yrs) patients underwent pancreas resection with AIT. Two patients had islet isolated remotely (Edinburgh and Kings College). Five received AIT for trauma (one total and four subtotal). Other indications included Chronic Pancreatitis (n=17) one of which had Familial Hyocalciuric Hypercalcaemia. Ten had gene mutations PRSS1 (n=6) or SPINK1 (n=4). Mean number of islets transplanted were 1534 IEQ/kg ranging in total from <5000- 443,000 IEQ. Patients with mutations received lower numbers of islets. Five remained insulin independent, overall 78% had measurable C peptide. 4/17 Chronic pancreatitis still have abdominal pain. Conclusion Pancreas resection combined with AIT is a viable treatment for both adults and children, even in those presenting with severe pancreatic trauma. Achieving good islet yields in patients with gene mutation remains a problem and is related to the extent of disease and duration of symptoms. Timing of TPIAT in these patients is critical if good outcomes are to be achieved.

Association between depression and diabetes among American adults using NHANES data from 2005 to 2020.

Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.

Abstract 4147634: Important Role of Prediabetes in Stroke Patients including ESUS

Stroke including ESUS is one of the common causes of disability and death worldwide. Furthermore, diabetes mellitus and prediabetes are among the main risk factors for cerebrovascular events. If the criteria for apparent diabetes mellitus is not met, a glucose metabolism disorder may still exist. Prediabetes can be present as impaired fasting glucose (IFG), impaired glucose tolerance or an increased, but not yet diabetic, HbA1c. To determine the frequency of diabetes mellitus (DM) and prediabetes mellitus (PDM) in patients with cardiovascular events, we analyzed the aspects of prediabetes in a stroke population of one of the largest stroke centers in Germany and collected the data in a prospective manner over 6 months. Among 714 included patients, 163 (30.8%) suffered a cryptogenic Stroke, including 98 (19%) ESUS. 185 (26%) TIA, 209 (39%) cardioembolic, 110 (21%) atherosclerotic, 40 (8%) lacunar and 7 (1%) other specific strokes were registered. >50% had a diabetic or prediabetic metabolic state, among which, the highest proportion was seen in lacunar strokes, followed by atherosclerotic infarctions. >80% of lacunar, >70% of atherosclerotic infarctions, 60% of ESUS, 50% of cardioembolic infarctions indicate DM or PDM. Both PDM and DM show a positive correlation with age. PDM is most common in 75-84y old patients. In the male population, PDM is most prevalent in the oldest patients (<85y) at >50%, and least prevalent in the youngest patients (<65y) at 15%. In this age group, women show a significantly higher frequency of DM and PDM. The highest number of female patients with glucose metabolism disorders is seen in the age group of 66-74y at >40%. In the oldest patient group, relatively speaking, more than twice as many men are affected by glucose metabolism disorders as women (52% vs. 24%). In summary the largest relative proportion of prediabetics and diabetics is seen at 80% among the lacunar infarction group and the second largest proportion at 70% among those with atherosclerotic infarctions. Among ESUS and cryptogenic stroke patients show a proportion of over 60% with impaired glucose tolerance. PD presents a positive correlation with increasing age, just like other risk factors. 40% of the 75-84-year-olds have DM or PDM. Therefore, diabetogenic micro- and macroangiopathies could be a major contributing factor to the causes of stroke.

Abstract 4136846: Sex Differences in Hypertension Diagnosis among Young Adults

Background: Young adults, especially men, may experience delays in diagnosis of hypertension, which subsequently affect timely treatment and control of high blood pressure (BP). Question: Compared with young adult women, how soon are young adult men diagnosed with hypertension after having high BPs during clinical encounters? Aim: To estimate the time to first diagnosis of hypertension in young adult men and women, and to identify factors associated with a delayed diagnosis of hypertension. Methods: Using electronic health records, we identified adults aged 18-39 years with systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, based on average of three consecutive separate outpatient BPs within two years of each other, between 2009-2016 from Kaiser Permanente Southern California. We followed them from the third qualifying BP until hypertension diagnosis, membership disenrollment, end of study (12/31/2019), or death, whichever occurred first. We used the cumulative incidence function and Cox proportional hazards models to estimate the time to first diagnosis of hypertension and identify factors associated with diagnosis. Results: Among 2,443 young adults (mean age 31 years, 57% men) with high BP, 37% were diagnosed with hypertension during a median of 5.9 years. Compared with women, a lower percentage of men were diagnosed with hypertension (30% vs 47%) and men received their diagnoses later (median time to diagnosis: 2.3 vs 1.4 years) ( Figure ). Among the total population, 19% of men and 12% of women did not have follow-up BP measures within one year following their third qualifying high BP. Among those diagnosed, 80% initiated with antihypertensive medications within one year following their diagnosis. Factors associated with a delayed diagnosis of hypertension included being male, younger, having lower systolic or diastolic BP, a lower body mass index, and the absence of dyslipidemia or (pre)diabetes. Conclusion: This study highlights that young adult men are at a higher risk of delayed hypertension diagnosis, emphasizing the need for healthcare system level interventions to improve the recognition, diagnosis, and treatment of hypertension in this population.

Incretin-responsive human pancreatic adipose tissue organoids: a functional model for fatty pancreas research.

Infiltration of adipocytes into the pancreatic parenchyma has been linked to impaired insulin secretion in individuals with increased genetic risk of T2D and prediabetic conditions. However, the study of this ectopic fat depot has been limited by the lack of suitable in vitro models. Here, we developed a novel 3D model of functionally mature human pancreatic adipose tissue organoids by aggregating human pancreatic adipose tissue-derived stromal vascular fraction (SVF) cells into organoids and differentiating them over 19 days. These organoids carry biological properties of the in situ pancreatic fat, presenting levels of adipogenic markers comparable to native pancreatic adipocytes and improved lipolytic and anti-lipolytic response compared to conventional 2D cultures. The organoids harbour a small population of immune cells, mimicking in vivo adipose environment. Furthermore, they express GIPR, allowing investigation of incretin effects in pancreatic fat. In accordance, GIP and the dual GLP1R/GIPR agonist tirzepatide stimulate lipolysis but had distinct effects on the expression of proinflammatory cytokines. This novel adipose organoid model is a valuable tool to study the metabolic impact of incretin signalling in pancreatic adipose tissue, revealing potential therapeutic targets of incretins beyond islets. The donor-specific metabolic memory of these organoids enables examination of the pancreatic fat-islet crosstalk in a donor-related metabolic context.

The impact of prediabetes on preclinical atherosclerosis in general apparently healthy population: A cross-sectional study

Background The hypothesis that not only diagnosed diabetes (DM), but also milder dysglycemia may affect the development of atherosclerosis still requires further study. In our population-based study, we aimed to evaluate the impact of prediabetic state on preclinical atherosclerosis and whether it may affect the cardiovascular risk (CVR) in the general population. Methods The analysis was a part of the Bialystok PLUS cohort study and represented a random sample of Bialystok (Poland) residents aged 20–79 years at the time of sampling (July 2017-January 2023). The cross-sectional analysis included 1431 participants of a population-based study (mean age 46.82 years). Comprehensive biochemical assessments were performed. An Oral Glucose Tolerance Test (OGTT) was performed on fasting patients who did not report having a DM. Results The population with prediabetes, based on HbA1c and OGTT, accounted for more than half of the study participants (n = 797, 55.7%). Atherosclerotic plaques in the carotid arteries were significantly more common in individuals with prediabetes considering all CVR categories. Prediabetes was associated with the occurrence of more advanced preclinical atherosclerosis, especially in the low to moderate CVR category. Serum glucose concentration after 1h and HbA1c proved to be statistically significant indicators of the presence of atherosclerotic plaques in ultrasound (respectively, AUC = 0.73 and 0.72). In multivariate logistic regression, prediabetes was independently associated with significantly increased risk of preclinical atherosclerosis (OR = 1.56, 95% CI 1.09–2.24), along with CVR categories, pulse wave velocity and central blood pressure augmentation index. Conclusions Prediabetes is associated with the occurrence and progression of the preclinical atherosclerosis. Importantly, many of those patients are in the low to moderate cardiovascular risk category, hence may have a severely underestimated risk. Inclusion of prediabetes into CVR assessment may improve risk stratification. An early identification of dysglycemic population is necessary to effectively implement the cardiovascular and metabolic prevention measures.

Routine HbA1c screening identifies de novo (pre)diabetes mellitus in 37% of ACS patients which comes with an even higher ischemic risk compared to known diabetes mellitus

Abstract Background Diabetes is a prominent risk factor for coronary artery disease (CAD). By exacerbating the progression of CAD, it puts these patients at increased risk of acute coronary syndrome (ACS) and recurrent ischemic events. It is therefore important to identify hyperglycaemic individuals and to treat them accordingly. However, in daily practice it is seen that a subsequent proportion of people with diabetes is undiagnosed. Purpose The aim of this research is to gain insight in the prevalence of patients with de novo (pre)diabetes, the treatment, and the risk of major adverse cardiac and cerebrovascular events (MACCE) compared to patients with known diabetes in an ACS cohort treated by percutaneous coronary intervention (PCI). Methods The Southeast Netherlands Heart Registry (ZON-HR) is an ongoing, multicentre registry collecting data of patients who underwent a PCI procedure. Of this cohort, patients presenting with ACS and measured HbA1c concentrations (on admission) were selected (N=1507). Patients with diagnosed diabetes are considered well-regulated when HbA1c <53 mmol/mol. Patients undiagnosed with diabetes were divided into three groups: HbA1c concentration <42 mmol/mol (normal), HbA1c 42-47 mmol/mol (pre-diabetes) and HbA1c ≥48 mmol/mol (diabetes). The rates of 30-day repeated myocardial infarction (MI), unplanned revascularisation, ischemic CVA, stent thrombosis, and cardiovascular mortality were determined, separately and combined as MACCE in patients with known diabetes compared to prediabetes and diabetes de novo. Results In the selected population, 28.5% of the patients were previously diagnosed with diabetes, which was well-regulated in only 30.2% of these patients. Of the patients not previously diagnosed, 23.1% and 14.4% had pre-diabetic and diabetic HbA1c concentrations, respectively. In 56.1% of patients with de novo diabetes, no glucose-lowering medication was prescribed at discharge (Table 1). At 30-day follow-up, de novo diabetes patients had increased rates of MACCE compared to patients with known diabetes (HR: 3.51, 95%CI 1.48-8.52) after multivariate analysis which corrected for differences at baseline (Figure 1). In addition, a significant increase in unplanned revascularisation (p=.014) and MI (p=.037) was found between de novo diabetes and known diabetes patients. Conclusions Almost half of the ACS patients in this cohort had either poorly regulated diabetes (305 patients) or was undiagnosed with (pre)diabetes while having an increased HbA1c concentration on admission (401 patients). Despite routine HbA1c screening, a subsequent part of these patients is not adequately treated for (pre)diabetes, especially the de novo diabetes patients. By this group, an even larger rate of MACCE was found, compared to the already established risk of diabetes in ACS. Therefore, active screening and treatment (as recommended in the guidelines) should get more attention to improve outcomes in these high-risk patients.Table 1:ACS population based on HbA1cFigure 1:Survival curves of 30D MACCE

Do poor psychosocial resources mediate health inequalities in type 2 diabetes? The Maastricht Study

Abstract Low socioeconomic position (SEP) has been identified as a risk factor for type 2 diabetes mellitus (T2DM). A potential pathway of this association is psychosocial resources. Disadvantageous environmental conditions result in low control beliefs through adverse resources and inferiority beliefs through social comparison for people with a low SEP. We examined two poor psychosocial resources, low control beliefs and inferiority beliefs, to explain socioeconomic inequalities in T2DM. We analysed mediating roles of low control beliefs and inferiority beliefs by using counterfactual mediation analysis. 8293 participants aged 40-75 living in Limburg, the Netherlands participated in The Maastricht Study starting from September 2010 to October 2020 and were followed up to 10 years with annual questionnaires with a median follow-up time of 7.18 years. SEP (education, income, occupation), control and inferiority beliefs, and (pre)diabetes by oral glucose tolerance test were measured at baseline. Incident T2DM was self-reported per annum. 3.2%(N = 203) of the participants without T2DM at baseline reported incident T2DM. People with low SEP had more often prevalent and incident T2DM (e.g., low education:HR=2.13, 95%CI:1.53-2.97). Lower control beliefs and higher inferiority beliefs were more common among people with low SEP than people with high SEP. Moreover, lower control beliefs and higher inferiority beliefs were risk factors for T2DM (e.g., low control beliefs: HR = 1.50, 95%CI:1.08-2.09). The relationship between SEP and T2DM was partially mediated by control beliefs (7.98-13.56%) and inferiority beliefs (2.16-4.53%). Poor psychosocial resources are important in socioeconomic inequalities in diabetes. Researchers and practitioners should consider the psychosocial profile of people with lower SEP might differ from those with higher SEP and this might interfere with the development, treatment, and prevention of T2DM. We should aim to work with such beliefs, instead of against it. Key messages • Socioeconomic health inequalities in diabetes has many underlying mechanism including psychosocial pathways. • Interventions and research should consider the different environment of low SEP and psychosocial profiles of people. We should aim to work with it, instead of against it.

The role of class stigma in socioeconomic inequalities in type 2 diabetes: The Maastricht Study

Abstract Background Low socioeconomic position (SEP) is a risk factor for type 2 diabetes mellitus (T2DM). An underlying mechanism behind socioeconomic health inequalities can be stigma, particularly classism. Studying the influence of class stigma in the context of (pre)diabetes and socioeconomic inequalities may shed light on the societal factors influencing diabetes. Methods Data from 1947 participants aged 49-88 who participated in the second phase of The Maastricht Study starting between November 2020 and April 2023 were used. SEP (education, income, occupation) and 6-item classism scale were measured through self-reported questionnaires. (Pre)diabetes was measured through an oral glucose tolerance test. We conducted multinomial logistic regression analyses to investigate the associations between SEP, classism, and diabetes status. Results 20.9% (N = 406) of the study sample had T2DM (Mage=69.8(±6.8) years; 31.3% women). People with low SEP had more often T2DM (e.g., income OR = 2.13, 95%CI:1.54-2.82) and reported perceived classism (e.g., education OR = 2.07, 95%CI:1.33-3.21) than people with high SEP. Classism was not statistically significantly associated with T2DM (OR = 0.78, 95%CI:0.48-1.29). Conclusions Social health inequalities are apparent in T2DM; however, our results suggest that class stigma might not be a major factor in underlying processes. Further research can investigate the role of chronic stress and intersection of multiple stigmas. Key messages • The underlying factors behind socioeconomic health disparities are complex. Social and psychological environment in low SEP should be investigated carefully. • Although low SEP is strongly associated with T2DM and perceived classism, class stigma might not be a major target in explaining socioeconomic pathways in diabetes.

Correlation between portal hypertension and somatic constitution: rationale behind the concept

This review summarizes recent data on the correlation of somatic constitution and portal hypertension.Somatotype reflects the constitutional composition of the human body. Excess endomorphic component (i.e. obesity) increases the risk of portal hypertension (PH - elevated pressure in the portal system above 12 mmHg) development. Among the prehepatic and posthepatic PH causes only congestive hepatopathy, a consequence of heart failure, is connected with obesity. A number of pathways connect the hepatic PH causes with obesity. Firstly, the action of proinflammatory cytokines produced by adipose tissue in greater amount in obesity promotes fatty acid uptake and storage by hepatocytes, leading to elevated oxidative stress and metabolic dysfunctions, activation of stellate cells, that differentiate into myofibroblasts and produce components of the intercellular matrix such as collagen into the perisinusoidal space resulting in fibrosis. Secondly, insulin resistance associated with obesity promotes dysfunction of the hepatic microcirculatory blood vessels, hyperlipidemia and liver steatosis. Thirdly, AMISS (Absence of Meal-induced Insulin Sensitization Syndrome), caused by regular high-carbohydrate and low-protein food consumption, manifested in decreased postprandial secretion of hepatic hormone hepatalin, which increases glucose uptake by skeletal and cardiac muscle, results in prolonged postprandial hyperglycemia, compensatory hyperinsulinemia and hyperlipidemia, leading to increased insulin resistance and a prediabetic state, associated with steatohepatosis. Thus, excess endomorphic component is to be regarded as a prognostic factor for portal hypertension.

Autonomic nervous system responses to hypo- and hyperglycemia in type 2 diabetes and prediabetes.

Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD) and normoglycemia (NG). Cross-sectional. Individuals with T2D (n=19, 7 men, HbA1c 49 mmol/mol), prediabetes (PD, n=18, 8 men) and normoglycemia (NG, n=17, 3 men) underwent one stepwise hyperinsulinemic-euglycemic-hypoglycemic and one hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV) and hemodynamics. The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both p<0.05) and there was a strong association with insulin resistance (p<0.05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both p<0.05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV-indices PLF and PHF at the target glucose plateau of 2.7 mmol/l (p<0.05), independent of BMI and HbA1c. Alterations in glucose-dependent responses of counter-regulatory hormones and the autonomic nervous system appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression.

Prevalence, Characteristics and Risk Factors Analysis of Prediabetes: A Cross-Sectional Study

Background Prediabetes, a reversible condition before the onset of diabetes, is a significant concern in healthcare globally. The global prediabetes epidemic has emerged and has considerably impacted health expenditures. Various risk factors play important roles in the progression of prediabetes to diabetes. Intensive lifestyle and pharmacological interventions can significantly reduce the risk of diabetes progression. Objective This study aimed to determine the prevalence, characteristics, and risk factors of prediabetes state of Medan in August 2023. Methods The sample consisted of 89 participants. This was an analytical cross-sectional study in the community that met the inclusion and exclusion criteria. The determination of prediabetes is based on the results of blood tests, namely, the examination of fasting blood sugar levels (FBGL), 2-hour postprandial oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1C). Other examinations included lipid profiling (total cholesterol, HDL-C, LDL-C, and triglycerides). Data processing was performed using SPSS via univariate and bivariate analyses (chi-square test). Results Of the 89 participants, the prevalence of prediabetes based on HbA1c, FBGL and 2-hours OGTT levels was 28.1%, 50.6%, and 28.1%, respectively. 82% of the participants were female, and 53.9% were overweight or obese based on body mass index (BMI). The risk factors for prediabetes were age &gt;64 years, female, physical inactivity, and diastolic blood pressure ≥90 mmHg (p&lt;0.05). Other risk factors such age &lt;45-64 years, consumption of vegetables/fruits, BMI, HDL, LDL, trygliceride, total cholesterol, systolic blood pressure, achantosis nigricans, and waist-hip circumference did not associate significantly (p&gt;0.05). Conclusion This study found that the prevalence of prediabetes was 67.4% in Medan. Age &gt;64 years, female, physical inactivity, and diastolic blood pressure ≥90 mmHg were the most important risk factors for prediabetes.

Prediabetes persistence or remission and subsequent risk of gallbladder cancer: A nationwide cohort study

Background & aimsHyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk. MethodsThis nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100–125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders. ResultsDuring 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank P < 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively. ConclusionsIndividuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC.

Utilizing the glucose challenge test during pregnancy as a predictor of future diabetes risk

BackgroundGestational Diabetes Mellitus (GDM) presents a significant health concern during pregnancy, predisposing individuals to future diabetes. Despite established postpartum diabetes screening guidelines, adherence to follow-up remains inadequate.AimsThis study aimed to assess the predictive value of the 50-gram glucose challenge test (GCT) for post-pregnancy diabetes development.Materials and methodsA population-based retrospective cohort study was conducted on pregnant women aged 18–45 who underwent GCT screening between November 2007 and July 2017 in a large Israeli community medical organization. Baseline characteristics, GCT results, and diabetes development during follow-up were analyzed using univariate and multivariate Cox regression analyses.ResultsAmong 8,675 women included, 2.4% developed diabetes over a median follow-up of 73.23 months. Elevated GCT results correlated with a higher risk of future diabetes, with a 4% rise in risk per 1 mg/dL increase in glucose above 140 mg/dL. Multivariate analysis revealed a 60-fold rise in the risk of future diabetes in women with GCT results ≥ 200 mg/dL compared to those with GCT < 140 mg/dL, adjusting for age, body mass index, pre-pregnancy glucose, cholesterol, and triglycerides. A GCT result between 140 and 199 mg/dL was a predictor of future diabetes, even when adjusted for GDM based on a subsequent GTT if performed.ConclusionsGCT results during pregnancy strongly predict future diabetes development, with higher GCT values significantly increasing risk. Recognizing abnormal GCT results as indicative of a prediabetic state offers a practical approach for risk stratification, facilitating early diagnosis, and intervention in post-pregnancy care.

Effect of continuous inhaled corticosteroids on glycated hemoglobin in asthmatic children: a pilot study

BackgroundAsthma is a prevalent chronic disease with significant impact on patients, families, and communities. Inhaled corticosteroids (ICS) are the mainstay of treatment for persistent and uncontrolled asthma. However, concerns remain about the potential adverse effects of ICS, including HbA1c level. This study aims to evaluate the influence of ICS on Hemoglobin A1c (HbA1c) levels in children with bronchial asthma.MethodsThis prospective cohort study included 48 pediatric asthma patients aged 2 to 15 years who had been using ICS for at least 6 months. Comprehensive clinical assessments and measurements of HbA1c levels were conducted at the start of recruitment and after 6 months of ICS use. The types and doses of ICS used followed the guidelines provided by the Global Initiative for Asthma (GINA).ResultsThe initial HbA1c levels ranged from 4.46 to 6.11, with a mean of 5.32 ± 0.35. Three patients (6.3%) had persistent prediabetes status after 6 months. There was no significant relationship between glycemic status and the characteristics of ICS. The duration of ICS therapy and the doses used did not significantly affect HbA1c levels. A weak positive correlation was observed between initial and subsequent HbA1c levels.ConclusionThe study found no significant difference in HbA1c levels among asthmatic children using ICS after six months of treatment. Additionally, there was no significant difference in HbA1c levels between patients using different types of ICS. Regular monitoring of HbA1c levels is recommended, particularly for children on high doses or prolonged use of inhaled Fluticasone.

12474 Demographic Characteristics Of Patients With Prediabetes Who Reverted To Normoglycemia Or Progressed To Diabetes At 1 Year Follow Up

Abstract Disclosure: E.M. Niedzialkowska: None. F. El Sayed: None. M. Townsend: None. U. Bhatia: None. S. Roy: None. R. Homayouni: None. A. Halalau: None. Background: Pre-diabetes (PD), characterized by hyperglycemia influenced by lifestyle factors, genetics, age, and ethnicity, is considered a risk factor for development of diabetes. However, only a small proportion of PD individuals progress to type-2 diabetes (T2D) each year. More refined diabetes risk prediction tools are needed to direct proactive health management strategies for at-risk populations. Question and Significance: Our study explored the associations between age, race, gender and BMI in PD individuals who either progressed to T2D or reverted to normoglycemia (NG) over a one-year follow-up period. Methods and Design: This is a retrospective observational study of 38,228 patients with PD, based on having two consecutive years of hemoglobin A1c (HbA1c) between 5.7% and 6.5%. We compared the demographic characteristics of individuals who progressed to T2D or regressed to NG within one year using bivariate (Kruskal-Wallis or Chi-squared) or multivariate logistic regression analysis. Results: The study cohort included 57.36% females, 66.13% Whites, 19.41% Blacks and 4.36% Asians with a median age of 69. Bivariate analysis revealed significant age differences between PD patients who reverted to NG with median age of 67 in those who reverted vs 70 in those who did not revert (p&amp;lt; 0.0001). In addition, the proportion of males who progressed to T2D was significantly higher and the proportion of Blacks who reverted to NG was significantly lower.Using multivariate regression (adjusting for age, gender, race and BMI), we found that each year in age significantly lowered the odds of reversion from PD to NG (OR 0.98, p&amp;lt;0.0001) but was not associated with progression to T2D. PD males had significantly higher odds of progression to T2D (OR 1.28, p&amp;lt;0.0001). Both Asians (OR 0.62, p&amp;lt;0.0007) and Blacks (OR 0.68, p&amp;lt;0.0004) had significantly lower odds of reversion to NG from PD compared to Whites. Surprisingly, BMI was not associated with neither reversion to NG nor progression to T2D, after adjusting for age, gender, and race. Discussion: Our findings underscore significant racial disparities and gender differences in regression to normoglycemia and progression to diabetes. This emphasizes the need for personalized interventions and targeted strategies for prediabetic populations to mitigate progression to T2D and to achieve normoglycemia. Presentation: 6/1/2024

Diabetes, Prediabetes, and Brain Aging: The Role of Healthy Lifestyle.

Diabetes is a well-known risk factor for dementia. We investigated the association between (pre)diabetes and older brain age and whether this can be attenuated by modifiable lifestyle behaviors. The study included 31,229 dementia-free adults from the UK Biobank between the ages of 40 and 70 years. Glycemic status (normoglycemia, prediabetes, or diabetes) was ascertained based on medical history, medication use, and HbA1c measured at baseline. Information on cardiometabolic risk factors (obesity, hypertension, low HDL, and high triglycerides) and lifestyle behaviors (smoking, drinking, and physical activity) was also collected at baseline. Participants underwent up to two brain MRI scans over 11 years of follow-up. Brain age was estimated using a machine learning model based on 1,079 brain MRI phenotypes and used to calculate brain age gap (BAG; i.e., brain age minus chronological age). At baseline, 13,518 participants (43.3%) had prediabetes and 1,149 (3.7%) had diabetes. Prediabetes (β = 0.22 [95% CI 0.10, 0.34]) and diabetes (2.01 [1.70, 2.32]) were both associated with significantly higher BAG, and diabetes was further associated with significant increase in BAG over time (0.27 [0.01, 0.53]). The association between (pre)diabetes and higher BAG was more pronounced in men and in people with two or more cardiometabolic risk factors. In joint exposure analysis, having a healthy lifestyle (i.e., no smoking, no heavy drinking, and high physical activity) significantly attenuated the diabetes-BAG association. Diabetes and even prediabetes are associated with accelerated brain aging, especially among men and people with poor cardiometabolic health. However, a healthy lifestyle may counteract this.

Oxidative stress and inflammation on metabolic abnormalities and renal involvement in prediabetic subjects across Europe

Background: Studying the mechanisms involved in the transition from prediabetes to diabetes and its associated complications, such as kidney disease, is a growing challenge. This study focuses on identifying valuable biomarkers for the early detection of kidney damage, evaluating molecules associated with oxidative stress and inflammation in prediabetic individuals across Europe.Methods: In plasma samples from individuals with prediabetes included in the ePREDICE study, we determined molecules related to oxidative stress (Advance oxidative protein products-AOPP) and inflammatory biomarkers (C-reactive protein-CRP; Interleukin 6-IL-6), and correlated them with anthropometric and biochemical data, assessing their potential for the early diagnosis of renal involvement.Results: Among the 967 people with prediabetes, 94 presented some sign of renal impairment such as albuminuria, hyperfiltration or hypofiltration. Significant variations were identified between oxidative stress and inflammatory biomarkers (upper and lower quartiles of AOPP, CRP and IL6), and parameters associated with blood pressure, glucose metabolism, lipid profile, and fatty liver index. In particular, both types of biomarkers were associated with components of the metabolic syndrome. There were significant associations between AOPP and CRP, and the presence of albuminuria, but not with renal function. Overall, CRP was a better biomarker than IL-6 for most of the parameters studied.Conclusion: These results highlight the important associations of oxidative stress and inflammation with metabolic abnormalities linked to the prediabetic state and its complications such as fatty liver and renal involvement. Although these results need to be confirmed, our study suggest that AOPP and CRP could be simple biomarkers of interest in predicting the risk of loss of renal function in people with prediabetes.

Associations of polysomnographic measures of obstructive sleep apnea, and nocturnal oxygen saturation with incident type 2 diabetes mellitus in middle-aged and older men.

Obstructive sleep apnea (OSA) has been associated with incident type 2 diabetes mellitus (T2DM); however, few prospective epidemiological studies have accounted for important T2DM predictors including pre-diabetes status and testosterone. Participants in the longitudinal Men Androgens Inflammation Lifestyles Environment and Stress (MAILES) study, who underwent eight-channel home-based polysomnography (PSG) in 2010-2011 (n = 824) and were free of diabetes at baseline were included in the analysis (n = 682). From 2015 to 2021, 78.6% (n = 536) completed at least one follow-up assessment. Incident T2DM was determined by self-reported doctor diagnosis, diabetes medications, plasma glucose (fasting ≥7.0 mmol/L or random ≥11.0 mmol/L) or glycated haemoglobin ≥6.5%. Conservative hierarchical Poisson regression models adjusted associations of PSG metrics (categorical and continuous) for age, waist circumference, baseline fasting glucose and testosterone concentrations. In all, 52 men (9.7%) developed T2DM over a mean (range) of 8.3 (3.5-10.5) years. Significant age- and waist circumference-adjusted association of incident T2DM with rapid eye movement (REM) sleep apnea-hypopnea index (AHI) ≥20 events/h (incidence rate ratio [IRR] 1.5, 95% confidence interval [CI] 0.8-2.8; p = 0.23] and highest quartile of delta index (IRR 2.1, 95% CI 0.95-4.6; p = 0.066) were attenuated after adjustment for baseline glucose and testosterone, and the association with the lowest quartile of mean oxygen saturation persisted (IRR 4.2, 95% CI 1.7-10.3; p = 0.029). Categorical measures of AHI severity, oxygen desaturation index, and hypoxia burden index (HBI) were not independently associated with incident T2DM. Associations with T2DM were similar when continuous PSG variables were used; however, HBI was significant (IRR 1.015, 95% CI 1.006-1.024; p = 0.007). In a sub-sample with OSA treatment data (n = 479), these significant associations persisted after excluding adequately treated OSA (n = 32). Understanding underlying OSA endotypes generating hypoxaemia may identify opportunities for diabetes prevention.

Genetic Predisposition to Prediabetes in the Kazakh Population.

The aim of this study was to conduct a comparative analysis of the population frequencies of the minor allele of polymorphic variants in the genes TCF7L2 (rs7903146) and PPARG (rs1801282), based on the genome-wide association studies analysis data associated with the risk of developing prediabetes, in an ethnically homogeneous Kazakh population compared to previously studied populations worldwide. This study utilized a genomic database consisting of 1800 ethnically Kazakh individuals who were considered in healthy condition. Whole-genome genotyping was performed using Illumina OmniChip 2.5-8 arrays, which interrogated approximately 2.5 million single nucleotide polymorphisms. The distribution of genotypes for the TCF7L2 (rs7903146) and PPARG (rs1801282) polymorphisms in the Kazakh sample was found to be in Hardy-Weinberg equilibrium (p > 0.05). The minor G allele of the "Asian" protective polymorphism rs1801282 in the PPARG gene was observed at a frequency of 13.8% in the Kazakh population. This suggests a potentially more significant protective effect of this polymorphism in reducing the risk of prediabetes among Kazakhs. The frequency of the unfavorable T allele of the insulin secretion-disrupting gene TCF7L2 (rs7903146) in Kazakhs was 15.2%. Studying the associations of genetic markers for prediabetes enables the timely identification of "high-risk groups" and facilitates the implementation of effective preventive measures. Further results from replicative genomic research will help identify significant polymorphic variants of genes underlying the alteration of prediabetes status.