Prediabetic Patients Research Articles

TSPO in pancreatic beta cells and its possible involvement in type 2 diabetes

Amyloidosis forms a large family of pathologies associated with amyloid deposit generated by the formation of amyloid fibrils or plaques. The amyloidogenic proteins and peptides involved in these processes are targeted against almost all organs. In brain they are associated with neurodegenerative disease, and the Translocator Protein (TSPO), overexpressed in these inflammatory conditions, is one of the target for the diagnostic. Moreover, TSPO ligands have been described as promising therapeutic drugs for neurodegenerative diseases. Type 2 diabetes, another amyloidosis, is due to a beta cell mass decrease that has been linked to hIAPP (human islet amyloid polypeptide) fibril formation, leading to the reduction of insulin production. In the present study, in a first approach, we link overexpression of TSPO and inflammation in potentially prediabetic patients. In a second approach, we observed that TSPO deficient rats have higher level of insulin secretion in basal conditions and more IAPP fibrils formation compared with wild type animals. In a third approach, we show that diabetogenic conditions also increase TSPO overexpression and IAPP fibril formation in rat beta pancreatic cell line (INS-1E). These data open the way for further studies in the field of type 2 diabetes treatment or prevention.

Efficacy and safety of glucagon-like peptide-1 receptor agonists on prediabetes: a systematic review and meta-analysis of randomized controlled trials

BackgroundPrediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.MethodsA comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.ResultsTwelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).ConclusionsGLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.

Association of high-sensitivity troponin T with left ventricular dysfunction in prediabetes

Background Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are an increasingly serious problem worldwide. Tissue Doppler imaging (TDI), a non-invasive technique, may evaluate both systolic and diastolic function during the first phases of cardiovascular disease (CVD). High-sensitivity cardiac troponin T (hs-cTnT) can detect subclinical myocardial injury in asymptomatic prediabetic patients. Aim We aimed to investigate the relationship between left ventricular (LV) function and hs-cTnT in prediabetic patients. Methods Between 1 October 2021 and 1 October 2022, we recruited 96 prediabetic and an equal number of age- and gender-matched healthy volunteers prospectively. TDI was used to evaluate both systolic and diastolic functions. Hs-cTnT levels were obtained and compared between groups. Results It was found that the values for mitral annular plane systolic excursion (MAPSE), E, the rapid filling wave, E/Em, and the peak annular velocities of systolic excursion in the ejection period (Sm) were all significantly higher in these patients compared to healthy individuals (p < .001). Hs-cTnT was an independent predictor of left ventricular diastolic dysfunction (LVDD) and left ventricular systolic dysfunction (LVSD) (odds ratio [OR] = 2.625, 95% confidence interval [CI] = 1.324–4.308, p < .001, and OR = 1.922, 95% CI = 0.454–3.206, p = .004). Conclusions Prediabetics had higher hs-cTnT levels than controls. We showed that LVSD and LVDD functions were negatively affected in prediabetic patients. Our results proved that hs-cTnT levels may be associated with subclinical LV dysfunction in prediabetes.

Improved Gut Health May Be a Potential Therapeutic Approach for Managing Prediabetes: A Literature Review.

Given the growing global threat and rising prevalence of type 2 diabetes mellitus (T2DM), addressing this metabolic disease is imperative. T2DM is preceded by prediabetes (PD), an intermediate hyperglycaemia that goes unnoticed for years in patients. Several studies have shown that gut microbial diversity and glucose homeostasis in PD or T2DM patients are affected. Therefore, this review aims to synthesize the existing literature to elucidate the association between high-calorie diets, intestinal permeability and their correlation with PD or T2DM. Moreover, it discusses the beneficial effects of different dietary interventions on improving gut health and glucose metabolism. The primary factor contributing to complications seen in PD or T2DM patients is the chronic consumption of high-calorie diets, which alters the gut microbial composition and increases the translocation of toxic substances from the intestinal lumen into the bloodstream. This causes an increase in inflammatory response that further impairs glucose regulation. Several dietary approaches or interventions have been implemented. However, only a few are currently in use and have shown promising results in improving beneficial microbiomes and glucose metabolism. Therefore, additional well-designed studies are still necessary to thoroughly investigate whether improving gut health using other types of dietary interventions can potentially manage or reverse PD, thereby preventing the onset of T2DM.

Measures of insulin resistance and beta cell function before and after treatment of HCV infection

The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, non-fibrotic CHC patients with a BMI <25 were enrolled in the study. Among them, 119 were successfully treated with either direct acting antiviral (DAA) drugs or pegylated interferon/ribavirin (IFN/RBV) anti-HCV therapy. Fasting state- and oral glucose tolerance test (OGTT)-derived indexes were used to evaluate β-cell function and insulin sensitivity. Among all subjects, 19 (13%) had T2DM and 21% exhibited pre-diabetes including 8% isolated impaired fasting glucose (IFG) and 13% combined IFG and impaired glucose tolerance (IGT). Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-cell function in CHC patients who achieved sustained virologic response (SVR), regardless of fasting or OGTT state. These findings emphasize the role of HCV in the development of β-cell dysfunction, while also suggesting that viral eradication can improve insulin secretion, reverse insulin resistance, and ameliorate glycemic control. These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.

EPH227 Identifying Prediabetes Patients Using Administrative Claims Linked with Lab Data to Assess Progression to Type 2 Diabetes

EPH227 Identifying Prediabetes Patients Using Administrative Claims Linked with Lab Data to Assess Progression to Type 2 Diabetes

Efficacy and safety of orlistat in controlling the progression of prediabetes to diabetes: A meta-analysis and systematic review.

The aim of this study is to examine the impact of the Orlistat on glucose levels and glucose tolerance in individuals with prediabetes, as well as assess its efficacy and safety in preventing the progression to diabetes. For achieving the appropriate randomized controlled trials, we enrolled the public datas from the following electronic databases: The Cochrane library, Embase, China National Knowledge Infrastructure, VIP, Wan-Fang, and China Biology Medicine disc. The article focused on the orlistat intervention of glucose tolerance and glycemic status in prediabetic patients. We restricted the publication time from the creation to May 2023. Six subjects were included in the study, with a total of 1076 participants (532 in the control group vs 544 in the experimental group). The results indicated that the orlistat can reduce the fasting blood glucose [relative risk (RR) = -2.18, 95% confidence intervals (CI) (-2.471, -1.886)], as well as the 2 hour postprandial blood glucose [RR = -1.497, 95% CI (-1.811, -1.183)]. Furthermore, it can prevent the impaired glucose tolerance patients to type 2 diabetes mellitus [RR = 0.605, 95% CI (0.462, 0.791)], and reversal the impaired glucose tolerance [RR = 2.092, 95% CI (1.249, 3.503)]. In prediabetic people, the orlistat can control weight, reduce the fasting blood glucose and the 2 hour postprandial blood glucose, and then delay the progression of diabetes. However, due to the quantitative restrictions, additional high-quality study needs to be conducted to improve the reliability of the results.

The relationship between adipose tissue RAAS activity and the risk factors of prediabetes in different ethnicities: A protocol for a systematic review and meta-analysis.

The incidence and prevalence of prediabetes has become a global concern. The risk factors of prediabetes, such as insulin resistance, adiposity, lipotoxicity and obesity, in conjunction with the alteration of the renin-angiotensin-aldosterone system (RAAS), have been positively correlated with the high morbidity and mortality rate. Thus, this systematic review seeks to establish the relationship between the risk factors of prediabetes, namely insulin resistance adiposity, lipotoxicity, obesity and the RAAS. Therefore, a synthesis of these risk factors, their clinical indicators and the RAAS components will be compiled in order to establish the association between the RAAS alteration and obesity in prediabetic patients. This protocol for a systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) standards. This will be accomplished by searching clinical Medical Subject Headings categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers will examine all of the findings and select the studies that meet the qualifying criteria. To check for bias, the Downs and Black Checklist will be used, followed by a Review Manager v5. A Forrest plot will be used for the meta-analysis and sensitivity analysis. Furthermore, the strength of the evidence will be assessed utilizing the Grading of Recommendations Assessment, Development, and Evaluation procedure (GRADE). The protocol has been registered with PROSPERO CRD42022320252. This systematic review and meta-analysis will include published randomized clinical trials, observational studies and case-control studies from the years 2000 to 2022.

Association between heme oxygenase-1 and hyperlipidemia in pre-diabetic patients: a cross-sectional study.

Although the importance and benefit of heme oxygenase-1 (HO-1) in diabetes rodent models has been known, the contribution of HO-1 in the pre-diabetic patients with hyperlipidemia risk still remains unclear. This cross-sectional study aims to evaluate whether HO-1 is associated with hyperlipidemia in pre-diabetes. Serum level of HO-1 was detected using commercially available ELISA kit among 1,425 participants aged 49.3-63.9 with pre-diabetes in a multicenter Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) prospective observational study. Levels of total cholesterol (TC) and triglyceride (TG) were measured and used to defined hyperlipidemia. The association between HO-1 and hyperlipidemia was explored in different subgroups. The level of HO-1 in pre-diabetic patients with hyperlipidemia (181.72 ± 309.57 pg/ml) was obviously lower than that in pre-diabetic patients without hyperlipidemia (322.95 ± 456.37 pg/ml). High level of HO-1 [(210.18,1,746.18) pg/ml] was negatively associated with hyperlipidemia (OR, 0.60; 95% CI, 0.37-0.97; p = 0.0367) after we adjusted potential confounding factors. In subgroup analysis, high level of HO-1 was negatively associated with hyperlipidemia in overweight pre-diabetic patients (OR, 0.50; 95% CI, 0.3-0.9; p = 0.034), especially in overweight women (OR, 0.42; 95% CI, 0.21-0.84; p = 0.014). In conclusion, elevated HO-1 level was negatively associated with risk of hyperlipidemia in overweight pre-diabetic patients, especially in female ones. Our findings provide information on the exploratory study of the mechanism of HO-1 in hyperlipidemia, while also suggesting that its mechanism may be influenced by body weight and gender.

#1831 Circulating MiRNA 195-5p may be associated with early renal impairment in patients with prediabetes

Abstract Background and Aims Type 2 diabetes mellitus (DM) is one of the leading causes of chronic kidney disease worldwide. However, there are few data concerning early kidney impairment in prediabetes patients. The aim of the study was to demonstrate early kidney damage in patients with prediabetes by assessing proximal tubule (PT) dysfunction, podocytes injury, and miRNA expression. Method A cohort of 192 individuals were analysed and divided such as follows: 52-normoalbuminuria-, 48-microalbuminuria-, and 50-macroalbuminuria type 2 DM patients, respectively; 12 patients-prediabetes and 30-healthy controls. The miRNA profile was assessed by real-time PCR, while PT dysfunction biomarker, N-acetyl-β-D-glucosaminidase (NAG), and podocyte injury biomarker, podocalyxin, were assessed by ELISA technique. The study was conducted in two distinct stages. In the first part of the study was detected a particular miRNAs profile in serum in patients with prediabetes; subsequently, the expression of the most relevant miRNA in patients with prediabetes was identified. Results i) in prediabetes patients, serum miRNA195-5p was 2.69 fold change as compared to the control group and correlated with NAG (p&amp;lt;0.05) and podocalyxin (p&amp;lt;0.03); ii) in type 2 DM patients, the expression of serum miRNA195-5p was higher and correlated with NAG (p&amp;lt;0.05), podocalyxin (p&amp;lt;0.04), urinary albumin: creatinine ratio (p&amp;lt;0.001) and with eGFR (p&amp;lt;0.001); iii) urinary NAG and urinary podocalyxin were higher in prediabetes patients and type 2 DM patients, even in the normoalbuminuria stage, as compared to controls (p&amp;lt;0.04; p&amp;lt;0.001). Conclusion A panel of molecular biomarkers, such as miRNAs, remain useful tools for the early diagnosis of renal involvement in the course of type 2 DM. MiRNA 195-5p may be associated with PT dysfunction and podocyte damage, and could predict renal dysfunction in both prediabetes and early diabetic kidney disease in type 2 DM patients.

Micronutrient Patterns and Low Intake of Vitamin A, Vitamin D, Folate, Magnesium, and Potassium Among Prediabetes and Type 2 Diabetes Patients.

Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk of diabetes-related complications. The study's objectives were to evaluate micronutrient intake in prediabetes (PD) and type 2 diabetes (T2DM) patients compared to recommended dietary intakes (RDI) and to determine the associations between the micronutrient patterns and both anthropometric measurements and biomarkers of diabetes. Methods This cross-sectional study was conducted on 349 patients with T2DM and 252 patients with PD. Micronutrient intake was evaluated using a validated food frequency questionnaire. Micronutrient patterns were extracted from factor analysis using principal component analysis with varimax rotation. Participants in the highest tertile were considered to have the highest adherence to the corresponding micronutrient pattern. Results T2DM patients had a significantly lower intake of vitamin E (9.4 ± 0.2 vs. 10.1 ± 0.3 mg; p = 0.048), vitamin D (44.3 ± 1.1 vs. 48.9 ± 1.7 IU; p = 0.020), and thiamin (1.3 ± 0.1 vs. 1.4 ± 0.1 mg; p = 0.013) compared to PD patients. All patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium and a significantly higher intake of vitamin B12 and copper compared to RDI. Three distinct micronutrient patterns were identified within each group. In the PD group, the Fe-Mn-Se pattern correlated significantly with waist circumference (WC) and fasting plasma glucose (FPG). The Vit.C-K-Folate pattern showed significant associations with body fat (BF). The Vit.B2-P-Vit.B12 pattern was significantly linked to WC, body mass index (BMI), BF, FPG, and serum insulin (SI). For the T2DM patients, the K-Folate-Mg pattern displayed an inverse and significant association with weight and WC. The Iron-Se-Vit.B3 pattern showed a significant association with low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol. The Vit.B2-P-Ca pattern was significantly associated with fasting plasma glucose (FPG). Conclusion This study demonstrated that T2DM patients had significantly lower vitamin E, vitamin D, and thiaminintake than PD patients. Both T2DM and PD patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium compared to the RDI. Among the identified micronutrient patterns, only the K-Folate-Mg pattern exhibited a significant association withreduced body weight and WC.

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials

BackgroundThere is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes.MethodsThis is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7–6.4% [40–47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof.ResultsOverall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1–4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95–2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29–2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15–10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years.ConclusionsIn patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years.Trial Registration NCT01471522, BioLINCC ID 13936.

Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes.

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

PREVALENCE OF INSULIN RESISTANCE IN PREDIABETIC PATIENTS WITH HYPERTENSION

stage between normal people and patients with type 2 diabetes mellitus. The pathogenesis is mainly related to insulin resistance (IR). The relationship between IR and hypertension is a complex and multifactorial phenomenon. We examined the prevalence of IR in prediabetic patients with hypertension. Objectives: The present study aimed to determine the incidence of IR according to the HOMA2 model in the group of prediabetes with hypertension, compared with the group of prediabetes without hypertension. Subjects and Methods: The cross-sectional study described and collected data from 191 people with prediabetes from February 2023 to September 2023 at the Examination Department of Cho Ray Hospital. IR was determined by the HOMA2 calculator, using a threshold of 1.29 for IR. Prediabetes and hypertension were diagnosed according to ADA 2022 and ISH 2020 criteria, respectively. Results: The number of subjects selected to analyze the data was 179 patients, including 89 prediabetes patients without hypertension and 90 prediabetes patients with hypertension. The prevalence of IR in the overall prediabetes group was 56.9%. The prevalence of IR in the hypertensive group was 66.7%, higher than the non-hypertensive group at 47.2%, which was statistically significantly different. The values of the index in HOMA2 did not differ statistically significantly between non-hypertensive and hypertensive populations. Conclusions: The prevalence of IR in prediabetes patients with hypertension was 66.7%, greater than the prediabetes patients without hypertension of 47.2%, P = 0.013. Attention should be paid to good control of blood pressure in patients with prediabetes.

Comparative analysis of the drugs efficacy for carbohydrate metabolism early disorders (prediabetes) treatment: A review

In the contemporary reality pharmacological correction of the early carbohydrate metabolism disorders is the main method for the type 2 diabetes prevention. Taking into account the main role of insulin resistance in the prediabetes development it can be supposed that pharmacological agents directly activating the insulin receptor are the pathogenic-base therapy for prediabetes treatment. Such kind of this pathogenic therapy is Subetta® – a representative of the class of biological drugs created using the based graduated technology. Due to the absent of the direct comparative trials of Subetta® versus metformin in the efficacy of the type 2 diabetes prevention in prediabetes patients, was performed an analysis of the effectiveness of these two drugs using the adjusted indirect comparison method of the results of the randomized double-blind placebo-controlled clinical trial of Subetta® efficacy and safety in impaired glucose tolerance patients with the results of several metformin studies similar in inclusion and efficacy criteria. The results indicate greater Subetta® efficacy in the treatment of glucose intolerance and metformin's – in the impaired fasting glucose treatment, which can be explained by the differences in the action mechanisms of these two drugs for prediabetes treatment.

Abstract PO4-12-12: An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Abstract Background: SOLAR-1 investigated use of alpelisib (ALP) + fulvestrant (FLV) in patients (pts) with hormone-receptor positive (HR+)/human epidermal growth factor-2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) after progression on endocrine-based therapy and demonstrated a clinically significant increase in all-grade (G) and G3-4 hyperglycemia (HG) compared to placebo + FLV. Current guidance recommends an insulin sensitizer (metformin, thiazolidinedione, SGLT2i) at HG onset. Given high rates of HG, a preventative protocol and identification (ID) of associated risk factors (RFs) was implemented to minimize HG, dose reductions and discontinuation. Although METALLICA investigated the implementation of metformin for hyperglycemia prophylaxis, there is limited data for alpelisib use and hyperglycemia prevention in high risk or controlled type 2 diabetic patients. Duke Breast Oncology Clinic (DBOC) implemented a preventive strategy to minimize HG and treatment disruptions in patients receiving alpelisib, including pre-diabetic and controlled-diabetic patients. Methods: This single-center, retrospective study included pts receiving at least one 28-day cycle of ALP+FLV between June 2019 and April 2023. One week prior to ALP initiation, pts initiated an insulin-sensitizer. Pts had fasting plasma glucose (FPG) levels drawn on day 8, 15, 28, and monthly while on ALP. The primary outcome was incidence of G2-4 HG. Descriptive statistics were used to summarize results. Number of RFs for HG (age ≥ 65 years, BMI ≥ 25 kg/m2, baseline FPG ≥ 100 mg/dL, and A1c ≥ 5.7%) were compared between pts with and without HG using Wilcoxon rank-sum test. Results A total of 30 pts (29 females; 1 male) were included with a median age of 60 years. The cohort was 70% White, 23% Black, while 67% were overweight/obese, and 50% had a history of type 2 diabetes mellitus (T2DM), gestational diabetes, or pre-diabetes. 29 pts received a CDK4/6 inhibitor prior to starting ALP. By day 28, 13 pts (43%) had G2-4 HG, with only 4 (13%) having G3 HG and zero having grade 4. Pts with G2-4 HG had a median of 2 RFs compared to only 1 RF if no HG. 8 pts (27%) required a temporary hold of ALP and 5 pts (17%) required a dose reduction in ALP due to HG. 25 pts permanently discontinued ALP; 14 due to disease progression and 8 due to an adverse event with only 3 due to HG. Median duration of ALP was 86 days (range 24-442), with 5 pts continuing to receive ALP at time of analysis. Patients with grade 2-4 HG by day 28 after ALP initiation had an older median age (66 years), higher BMI (median 28.1 kg/m2), higher baseline FPG (median 100 mg/dL), and higher baseline HbA1c (median 5.6%) compared to those without grade 2-4 HG (Table). Conclusions: Implementation of a HG prevention protocol with ALP in the real-world setting demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (13% vs 36.6%) but slightly higher than METALLICA (6%) although we included a higher risk patient population. An increase in HG-associated RFs correlated with a higher incidence of G2-4 HG. Early risk identification and optimization of prophylactic antihyperglycemics can reduce ALP dose reductions and discontinuations secondary to HG. ALP use in higher-risk patients can be considered with a HG prevention protocol. Table 1. Hyperglycemia outcomes Citation Format: Heather Moore, Sarah Burnette, Emily Poehlein, Hui-Jie Lee, Kelly Westbrook, Thomas Bagwell, Kervin Novido, Susan Dent. An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-12.

Metabolomics Signature in Prediabetes and Diabetes: Insights From Tandem Mass Spectrometry Analysis.

This study investigates the metabolic differences between normal, prediabetic and diabetic patients with good and poor glycaemic control (GGC and PGC). In this study, 1102 individuals were included, and 50 metabolites were analysed using tandem mass spectrometry. The diabetes diagnosis and treatment standards of the American Diabetes Association (ADA) were used to classify patients. The nearest neighbour method was used to match controls and cases in each group on the basis of age, sex and BMI. Factor analysis was used to reduce the number of variables and find influential underlying factors. Finally, Pearson's correlation coefficient was used to check the correlation between both glucose and HbAc1 as independent factors with binary classes. Amino acids such as glycine, serine and proline, and acylcarnitines (AcylCs) such as C16 and C18 showed significant differences between the prediabetes and normal groups. Additionally, several metabolites, including C0, C5, C8 and C16, showed significant differences between the diabetes and normal groups. Moreover, the study found that several metabolites significantly differed between the GGC and PGC diabetes groups, such as C2, C6, C10, C16 and C18. The correlation analysis revealed that glucose and HbA1c levels significantly correlated with several metabolites, including glycine, serine and C16, in both the prediabetes and diabetes groups. Additionally, the correlation analysis showed that HbA1c significantly correlated with several metabolites, such as C2, C5 and C18, in the controlled and uncontrolled diabetes groups. These findings could help identify new biomarkers or underlying markers for the early detection and management of diabetes.

Profiling of circulating-MicroRNAs’ signatures in pre-diabetic versus diabetic patients

Profiling of circulating-MicroRNAs’ signatures in pre-diabetic versus diabetic patients

Evaluation of Serum Level of Galectin-3 in Prediabetic and Type-2 Diabetic Patients With and Without Vascular Complications

Evaluation of Serum Level of Galectin-3 in Prediabetic and Type-2 Diabetic Patients With and Without Vascular Complications

Positive Association of Pulse Pressure with Presence of Albuminuria in Chinese Adults with Prediabetes: A Community-Based Study.

Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.