Prediabetic Patients Research Articles

25-OR: Machine Learning for Early Detection of Nonresponders to Lifestyle Intervention for Prediabetes

Introduction: Lifestyle intervention is the first-line treatment for prediabetes. More intensive intervention usually follows for those patients that fail to improve glycemia. We explored the possibility to early detect non-responders to lifestyle intervention from a single baseline evaluation. Methods: The sample was composed of 738 pre-diabetic (fasting glucose 100-125 mg/dl) patients (median age 54 IQR 45-62, 57% female, median BMI 30.4 IQR 27.5, 34.2) , that were prescribed a lifestyle intervention, and were re-evaluated within 12 months. Lifestyle intervention consisted of a hypocaloric diet (based on resting energy expenditure measured by indirect calorimetry, with a Mediterranean pattern, tailored on patient habits) and WHO physical activity guidelines. The outcome was normalization of fasting glucose at follow-up (0: ≥100 mg/dl, 1: <100 mg/dl) , with an historical failure rate of 44%. Baseline evaluation consisted of anthropometry, indirect calorimetry, abdominal fat ultrasound, laboratory exams, structured medical and nutritional interview, and psychological questionnaires, with a total of 114 predictors. Statistical and machine learning models were screened to select the best classifier for the outcome. Results: The best model was a random forest model (a machine learning model) , with a validation-set accuracy of 72%, ROC AOC of 0.64, sensitivity of 55%, and specificity of 86%. Discussion: The best developed model is able to identify more than half non-responders on the basis of a single baseline evaluation, while including few responders as false-positives. The model accuracy resulted higher than the historical rate of failure, so integrating the model suggestion in the clinical decision process should allow to more promptly treat future patients and improve the overall success rate. Machine learning models show potential in leveraging high-dimensional multi-domain routinely-collected clinical data to aid in clinical decision. Disclosure A.Foppiani: None. R.De amicis: None. A.Leone: None. S.Bertoli: None. A.Battezzati: None.

4-OR: IL6R Signaling in Adipogenesis Mediates GLP-1 Analog Effects on Adipose Tissue Beiging

Mechanisms underlying antidiabetes effects of GLP-1 analogs such as liraglutide, collectively termed incretins, remain incompletely understood. While incretins boost insulin secretion, they also modulate the immune system and have anti-obesity effects. We discovered that prediabetic patients treated with incretins have increased thermogenic gene expression in supraclavicular adipose tissue (AT) . Interestingly, incretin-treated patients were found to have elevated levels of IL6 plasma, consistent with the observation that incretin treatment induces IL6 secretion by human monocytes. We hypothesized that incretins induce adipocyte browning via IL6 and used the mouse model to test if IL6 receptor (IL6Ra) signaling underlies the effects of the incretin-IL6 axis. We show that liraglutide transiently increases IL6 in circulation and ILRa signaling in AT while metronomic liraglutide treatment results in AT browning and improved glucose clearance in mice. IL6-blocking antibody treatment inhibited the thermogenic and antidiabetes effects of liraglutide. Based on the observation that IL6 induces thermogenic gene expression in cultured adipocytes, we hypothesized that the incretin-IL6 axis directly induces adipocyte browning. To test this, we generated mice with IL6Ra knockout in Pdgfrb-positive adipocyte progenitors (APC-KO) and in adipocytes (AD-KO) . We show that liraglutide-induced weight loss does not depend on IL6 signaling in the adipocyte lineage. However, both IL6Ra APC-KO and AD-KO mice failed to undergo thermogenic adipocyte browning and glucose utilization increase in response to liraglutide treatment. We conclude that the antidiabetes effects of metronomically administered incretins are mediated by transient upregulation of IL6, which activates canonical ILRa signaling and thermogenesis in adipocytes. Disclosure A.D.Gutierrez: None. Z.Gao: None. Y.Yu: None. M.Kolonin: n/a. Funding National Institutes of Health (NIDDK 5R21DK122234)

50-OR: Peer Support Improves Health Behaviors in People with Prediabetes

Up to one third of Americans have prediabetes, a condition of elevated glucose levels linked with greater diabetes incidence. Strong evidence shows that peer support is an effective strategy to improve outcomes for people with diabetes; however, no studies have examined whether peer support can be leveraged to improve outcomes in people with prediabetes. The “Using Peer Support To Aid in Prevention and treatment of Prediabetes (UPSTART) ” study is a pragmatic randomized controlled trial at Kaiser Permanente Northern California and the University of Michigan that randomized 351 people with prediabetes (A1c 5.7-6.4; BMI >25 or BMI >23 for Asian patients) from 10/19/2018-3/31/2021 to one of two study arms: a peer support intervention with 1:1 matching of prediabetes patients with coaches trained in motivational interviewing (intervention group) ; or enhanced usual care (control group) . All participants received information on healthy eating, active living, wellness, and diabetes prevention programs. Lifestyle and psychosocial factors were measured via baseline and six-month surveys. In our sample, 2of study patients were female; 1were Black; 147 were White; 31 were Hispanic/Latino; 30 were Asian; 24 were Multiracial or ‘Other’ race. At six months, intervention participants had higher participation in diabetes education and prevention programs (25.2% vs. 11.1%, p=.002) ; higher Patient Activation Measure (PAM) scores (68.9 vs. 65.7 on a 0-100 scale, p=.043) ; greater perceived social support (55.3 vs. 49.6 on a 12-72 scale; p<.001) ; and greater whole grain consumption (19.2 vs. 14.5 days out of 30; p=.024) compared to controls. There were no differences in physical activity, vegetable, fruit, or soda consumption at six months. A peer-support program for people with prediabetes has a positive impact on factors linked to diabetes prevention and better health outcomes. Future research from this study will examine whether the intervention and these improvements are also associated with decreased A1c and weight. Disclosure J.Schmittdiel: None. H.Finertie: None. L.A.Rodriguez: None. T.Thomas: None. P.Sanchez: None. M.Heisler: n/a. Funding National Institutes of Health (R18DK113403)

Chairside Screening for Undiagnosed Diabetes and Prediabetes in Patients with Periodontitis.

Introduction Globally, it is estimated that half of all people with diabetes are undiagnosed. Because of the well-documented bidirectional link between diabetes and periodontitis, dentists and dental hygienists may have the possibility to screen a targeted population for diabetes during routine dental visits. The aim of the present study is to investigate the effectiveness of one device for diagnosis of diabetes/prediabetes used in one private dental practice and investigate the correlation between the levels of HbA1c and periodontal parameters. Methods Periodontal patients that were never diagnosed with diabetes were asked to fill a risk assessment questionnaire for type 2 diabetes mellitus. PD, CAL, FMBS%, FMPS%, and HbA1c through a prick-finger test were measured before and after periodontal therapy or only once in patients following supportive periodontal therapy. Results A total of 98 subjects were screened, and among them, one had diabetes and 30 had prediabetes. The mean value of HbA1c was 5.62% for patients with untreated periodontitis and 5.42% for periodontally treated patients. The diagnosis of diabetes resulted to be correlated to FMBS% and FMPS%, while HbA1c levels were correlated to FMBS%, FMPS%, and periodontitis grade. Conclusion The present chairside diabetes-screening protocol allowed a consistent proportion of patients to become aware of their pathological or prepathological condition and to seek proper and timely medical care. Thus, dentists and dental hygienists could provide health promotion services and preventive measures.

Pre-diabetes increases the risk of heart failure among patients with nonvalvular atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart failure (HF) is common in patients with nonvalvular atrial fibrillation (NVAF) which is associated with excess morbidity and mortality. Notably, the presence of diabetes increases risk of HF in patients with NVAF. The association between pre-diabetes and risk of HF was nonetheless unexplored in this population. Purpose The present study aimed to evaluate whether pre-diabetes was associated with an increased risk of HF in patients with NVAF. Methods Using a previously validated territory-wide electronic health record database, patients with newly diagnosed NVAF from 2010 to 2018 were included to evaluate for risk of HF upon competing risk regression with Cox proportional-hazard model adjustment. Patients were divided into 3 groups according to their baseline glycemic status: (1) type 2 diabetes, (2) pre-diabetes, and (3) normoglycemia. In the pre-diabetes group, the subsequent risk of HF was further evaluated according to the changes of glycemic status at two years following index date. Results Among 65,994 NVAF patients (mean age 75.7 years, 48.5% female), 27,706 (42.0%) were normoglycemic, 10,926 (16.6%) had pre-diabetes, and 27,312 (41.4%) had diabetes at baseline. Over a median follow-up of 7.1 years, 7,203 (26%) normoglycemic patients, 3,168 (29%) pre-diabetic patients, and 8,745 (32%) diabetic patients developed HF (Log rank test, P<0.001). Pre-diabetes was associated with an increased risk of HF compared with normoglycemic patients (subdistribution Hazard Ratio (SHR) = 1.09, 95% confidence interval (CI): 1.04-1.14) and diabetes conferred the highest risk amongst three groups (SHR=1.19, 95%CI: 1.15-1.24). In patients with pre-diabetes at baseline, 873 (8.0%) progressed to diabetes and 1204 (11%) resolved to normoglycemia at 2 years. Compared to those who remained pre-diabetic, patients who progressed to diabetes had a higher risk of HF (SHR = 1.23, 95% CI :1.05-1.44), whereas those who resolved to normoglycemia incurred a lower risk (SHR = 0.80, 95% CI :0.68-0.94). Conclusion(s) Pre-diabetes was independently associated with an increased risk of HF in patients with NVAF. Pre-diabetic patients who progressed to diabetes at 2 years experienced an increased risk of HF, whereas those who resolved to normoglycemia reduced risk of HF, as compared to those who remained pre-diabetic. These findings highlight the importance of strict blood glucose control in reducing the risk of HF in patients with atrial fibrillation.

Changes in TRG/ApoA-1 ratio, TRG/HDL-C ratio and lipid serum profile after combination therapy with telmisartan/amlodipine in prediabetic patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose The combination of telmisartan with amlodipine is a commonly administered combination of an agonist ATII (angiotensin receptor II) and CCB (calcium channel blocker) for the management of hypertension. The purpose of this study is to evaluate the effect of the fixed of combination telmisartan/amlodipine 80/5mg per day on the levels of serum lipids, as well as the levels of serum apolipoproteins and the TRG/ApoA-1, TRG/HDL-C ratios, in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-180 mmHg and/or diastolic blood pressure (DBP) 100-110 mmHg) and with prediabetes (IFG/IGT), before and after the 3-month treatment. Methods Data from 51 patients who had visited our outpatient clinic for lipid metabolism disorders during the period 2014-2018 and had been randomized in the telmisartan/amlodipine group 80/5mg per day. The patients (35 male/16 female) had BMI: 29.32 [27.37-31.65]. The levels serum lipids and of apolipoproteins B, A1, Lp(a) and E were measured before the beginning of the treatment and 3-months after its administration. Results The resulting variations of SBP and DBP levels before and after the 3-month treatment, as well as the variations of serum lipid, apolipoprotein levels and TRG/ApoA-1, TRG/HDL-C ratios are presented on Table 1. Conclusion The 3-month telmisartan/amlodipine therapy seems to improved, statistically significant both SBP and DBP levels (decreased by -13.58 % and -13 % respectively, p<0.001, for both values). Serum lipid levels didn’t show any significant variation before and after treatment. Statistically significant changes were not present in apolipoprotein levels, also. Finally, there were no statistically significant variations in either TRG/ApoA-1 or TRG/HDL-C ratios.

Changes in TRG/ApoA-1 ratio, TRG/HDL-C ratio and lipid serum profile after combination therapy with valsartan/amlodipine in prediabetic patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose The combination of valsartan with amlodipine is a commonly administered combination of an agonist ATII (angiotensin receptor II) and CCB (calcium channel blocker) for the management of hypertension. There is already data from different studies that describe the effect of each of those medications in the lipidemic profile. Ratios TRG/ApoA-1, TRG/HDLC are useful markers of insulin resistance. The purpose of this study is to investigate the effect of the fixed combination of valsartan/amlodipine 160/5mg per day on the levels of serum lipids, as well as the levels of serum apolipoproteins and the TRG/ApoA-1, TRG/HDLC ratios, in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-179 mmHg and/or diastolic blood pressure (DBP) 100-109 mmHg) and prediabetes (IFG/IGT), before and after the 3-month treatment. Methods Data from 54 patients who were referred to our outpatient clinic for lipid metabolism disorders during the period 2014-2018 and had been randomized in the valsartan/amlodipine group 160/5mg per day. Those patients (33 male/21 female from whom 14 were smokers and 8 alcohol users) all completed the study successfully with mean BMI: 28.09[26.81-29.89]. The median values of SBP and DBP for the sample group were: 162 [159.25-165] και 100 [92-103.75] mmHg, respectively. The levels of apolipoproteins B, A-1, Lp(a) and E were measured prior to the beginning of treatment and 3-months after its administration. Results The resulting alternations of SBP and DBP levels before and after the 3-month treatment, as well as the changes of serum lipid, apolipoprotein levels and TRG/ApoA-1, TRG/HDL-C ratios are presented in Table 1. Conclusions From the sample group it seems like that the 3-month therapy with valsartan/amlodipine improved statistically significant both SBP and DBP levels (decreased by -13.58% and -13% respectively, p<0.001 for both values). Concerning lipid levels, no significant variation was observed across the board. Finally, no significant change was observed in apolipoprotein levels and TRG/ApoA-1, TRG/HDL-C ratios.

Admission HbA1c and post-MI prognosis in patients without known diabetes: a meta analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background The association between newly diagnosed abnormal HbA1c and post-MI prognosis is unclear. Previous meta-analyses have included studies with both diabetic and non-diabetic patients or subsets of these patients. Purpose To assess the association between HbA1c and post-MI prognosis in patients without known diabetes. Method Cohort studies (up to Oct 2021) were retrieved from PubMed and Embase. We included studies that compared events in patients with newly diagnosed hyperglycaemia on admission HbA1c to those without. Studies where the hyperglycaemic groups had mixed known and newly diagnosed patients were excluded. Pooled risk ratios (RRs) and the 95% confidence interval (CI) were calculated using random effect model to assess the association between newly diagnosed diabetes and pre-diabetes and in-hospital, 30-day and ≥1-year mortality and MACE. Results 29 studies comprising 279719 patients were included. The pooled RR for in-hospital, 30-day and ≥1 year mortality in diabetic patients (Fig 1) were 1.94 [1.41-2.67], p<0.0001; 1.55 [1.02-2.34], p=0.04 and 1.69 [1.50-1.90], p<0.0001 respectively. Corresponding data for MACE were 1.78 [0.51, 6.18], p=0.36; 1.14 [1.01-1.28], p=0.03 and 1.40 [1.19-1.65], p<0.0001. In prediabetic patients (Fig 2), the corresponding RR for mortality was 1.28 [1.06, 1.55], p=0.009; 1.05 [0.85, 1.29], p=0.66 and 1.49 [1.21, 1.84], p=0.0002 and for MACE it was 4.63 [1.80, 11.90], p=0.001; 1.19 [1.05, 1.36], p=0.008 and 1.57 [1.24, 1.99], p=0.0002. Conclusions High HbA1c at admission in patients without known diabetes is associated with worse post-MI outcomes both in diabetic and prediabetic groups.

Alternations in markers of insulin resistance: HOMA-IR, HOMA-B, QUICKI, after dual therapy combination with valsartan/amlodipine in prediabetic hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose The combination of valsartan with amlodipine is more effective than monotherapy for managing HT. The purpose of this study was to investigate the effect of the fixed combination of valsartan/amlodipine 160/5 mg per day on HOMA-IR (homeostatic model assessment for insulin resistance), HOMA-B (HOMA for β cell function) and QUICKI (quantitative insulin-sensitivity check index) values in patients with stage 2 hypertension (systolic arterial pressure 160-179 mmHg and/or diastolic pressure 100-109 mmHg) and prediabetes (IFG/IGT) before and after 3 months of treatment with the dual therapy. Methods Data from 54 patients who visited our outpatient clinic for lipid metabolism during the period 2014-2018. 54 persons were randomized in the valsartan/amlodipine group 160/5 mg per day (33 males/21 females from whom 14 were smokers and 8 were alcohol consumers) with BMI: 28.09[26.81-29.89], all of whom successfully completed the study. The median values of systolic and diastolic arterial pressure for the study population: 162 [159.25-165] and 100 [92-103.75] mmHg, respectively. Results The resulting variations of systolic and diastolic arterial pressure as well as the variations of HOMA-IR, HOMA-B and QUICKI are presented on Table 1. Conclusions From the studied group it is concluded that the 3-month treatment with valsartan/amlodipine improved with statistical significance the values of both systolic and diastolic arterial pressure (reduction by -13.58% and -13% for systolic and diastolic arterial pressure, respectively, p<0.001, for both values). Regarding glucose levels, there has also been a reduction by -0.04%, without statistical significance, while the increase of insulin levels (+16.13%) by the end of the 3-month period was also deemed statistically insignificant. Additionally, there have been noted statistically insignificant increases in HOMA-IR (+12.65%) and HOMA-B (+17%). Finally, no change has been observed in QUICKI values.

Alternations in markers of insulin resistance: HOMA-IR, HOMA-B, QUICKI, after dual therapy combination with delapril/manidipine in prediabetic hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Purpose The administration of the 30mg hydrochloric delapril and 10mg hydrochloric manidipine formulation is indicated for patients with idiopathic hypertension whose arterial pressure cannot be sufficiently managed with monotherapy. The purpose of this study is to investigate the effect of the premade combination delapril/manidipine 30/10mg per day on the variation of HOMA-IR, HOMA-B and QUICKI values, in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-180 mmHg and/or diastolic blood pressure (DBP) 100-110 mmHg) and with prediabetes (IFG/IGT) before and after the 3-month treatment with the fixed combination dual-therapy. Methods 53 patients (30 male/23 female, from whom 12 smokers and 7 alcohol users) who visited our outpatient clinic for lipid metabolism disorders and fulfilled the study’s criteria joined the study’s sample. They were randomized in the delapril/manidipine group. The patients’ BMI was 28.73 [27.73-30.3] and the SBP and DBP values were: 156 [151-161] and 100 [88-101] mmHg respectively. Results The resulting variations of SBP and DBP levels, as well as the variations of glucose and insulin levels and HOMA-IR, HOMA-B and QUICKI are presented on Table 1. Results From the sampled patients it seems that the 3-month treatment with delapril/manidipine improved statistically significantly the levels of both SBP and DBP (reduction by -11.54% and -12% respectively, p<0.001 for both values). Glucose levels witnessed a 1.55% decrease with statistical significance while a notable increase in insulin by 4.65% was also observed after the 3-month treatment, albeit without any statistical significance. Concerning HOMA-IR and QUICKI, there were no significant variance, while HOMA-B values showed a statistically significant increase (7%, p=0.006)

Changes in TRG/ApoA-1 ratio, TRG/HDL-C ratio and lipid serum profile after combination therapy with manidipine/delapril in prediabetic hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose Both manidipine and delapril have been proven to have a neutral effect on lipids. Patients with idiopathic hypertension are being administered with the 30mg hydrochloric delapril and 10mg hydrochloric manidipine formulation. The purpose of this study was to investigate the effect of the fixed combination of delapril/manidipine 30/10mg on lipid and apolipoprotein levels as well as on TRG/ApoA-1 and TRG/HDL-C ratios as indicative markers of insulin resistance, in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-179 mmHg and/or diastolic blood pressure (DBP) 100-109 mmHg) and with prediabetes (IFG/IGT), before and after the 3-month treatment. Methods 53 patients referred to our outpatient clinic for lipid metabolism disorders and met the study’s criteria were included, during the period 2014-2018. In the group of delapril/minidipine there were randomized 30 males and 23 females from whom 12 were smokers and 7 alcohol users). The patients’ BMI was 28.73 [27.73-30.3] and the values of SBP and DBP were: 156 [151-161] και 100 [88-101] mmHg, respectively. The serum lipid and apolipoprotein levels were measured before and after the 3-month treatment. Results The resulting variations of SBP and DBP levels, as well as the changes in lipid levels, apolipoprotein levels and TRG/ApoA-1 and TRG/HDL-C ratios are presented on Table 1. Conclusion From the sample group it can be observed that the 3-month combination therapy with manidipine/delapril improved statistically significantly both SBP and DBP levels (reduction by -13.58% and -13%, respectively). Concerning serum lipid levels, the combination therapy statistically significantly improved TCHOL, LDL-CHOL, and non-HDL-CHOL levels (decrease by 4.01%, 6.7% and 5.4%, p= 0.009, 0.006 and 0,08 respectively). The changes in apolipoprotein values were small and only ApoB values showed a statistically significant variation. Finally, there wasn’t a statistically significant improvement on neither TRG/ApoA-1 nor TRG/HDL-C ratios.

Alternations in markers of insulin resistance: HOMA-IR, HOMA-B, QUICKI, after dual therapy combination with telmisartan/amlodipine in prediabetic hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction-Purpose The combination of telmisartan and amlodipine in tablet form indicated for patients whose arterial blood pressure cannot be fully managed with monotreatment. The purpose of this study was to investigate the effect of the fixed combination telmisartan/amlodipine 80/5mg per day on arterial pressure levels and the variation of HOMA-IR, HOMA-B and QUICKI values in patients with stage 2 hypertension (systolic blood pressure (SBP) 160-179 mmHg and/or diastolic blood pressure (DBP) 100-109 mmHg) and with prediabetes (IFG/IGT) before and after the 3-month treatment with the administration of the fixed combination. Methods Data collected from 51 patients who have visited our outpatient clinic for lipid metabolism disorders during the period 2014-2018. 51 persons with BMI: 29.32 [27.37-31.65] (25 male, 16 female) had been randomized in the group for telmisartan/amlodipine 80/5mg per day. The median values for the study’s sample in SBP and DBP were: 163[158-168] and 100[95-106] mmHg, respectively. Their somatometric and demographic characteristics were recorded in the beginning of the study and are presented on Table 1Α. Results The results of the variations in SBP and DBP, as well as the variations in glucose, insulin, HOMA-IR, HOMA-B and QUICKI before and after the 3-month treatment are presented on Table 1B. Conclusions From the sampled patients it can be observed that the 3-month treatment with telmisartan/amlodipine statistically significantly improved (p=0.005) the HOMA-IR values while improving fasting glucose and insulin levels. Finally, there was a statistically significant reduction in QUICKI values and a statistically insignificant reduction in HOMA-B.

Effects of Hypertension on Two-Year Outcomes According to Glycemic Status in Patients With Acute Myocardial Infarction Receiving Newer-Generation Drug-Eluting Stents.

The effects of hypertension on long-term outcomes according to glycemic status in patients with acute myocardial infarction (AMI) after successful implantation of newer-generation drug-eluting stents (DES) have not been fully investigated. In this retrospective cohort study, a total of 11,911 patients were classified into 6 groups according to their glycemic status and presence or absence of hypertension. The major outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any revascularization. In patients without hypertension, the major outcomes were similar between the normoglycemia and prediabetes groups. However, MACE, all-cause death, cardiac death (CD), Re-MI rates were higher in patients with type 2 diabetes mellitus (T2DM) than in normoglycemic patients. Additionally, Re-MI was higher in patients with T2DM than in prediabetic patients. In patients with hypertension, although the major outcomes were similar between the prediabetes and T2DM groups, in both the prediabetes and T2DM groups, MACE, all-cause death, and CD rates were higher than those in the normoglycemia group. During a 2-year follow-up, the comparable harmful effects of hypertension in patients with AMI and prediabetes or T2DM were observed. Effective blood pressure and glucose control should be strengthened to reduce mortality in these patients.

Prediabetic patients evaluated with Quantose™ IR and their relationship with anthropometric measurements through bioelectrical impedance analysis

Introduction: New metabolomic biomarkers as Quantose™ IR and anthropometric measurements using bioelectrical impedance analysis (BIA) provide relevant information on patients with insulin resistance and prediabetes. QuantoseTM IR is a novel metabolomic test to assess insulin resistance for screening and monitoring. Establishing a correlation between these variables is useful in clinical practice and, to our knowledge, there are no published studies that explore the relationship between Quantose™ IR and anthropometric measurements using BIA in patients with prediabetes. Objective: To evaluate the correlation between Quantose™ IR and BIA anthropometric variables (fat mass, FM; fat mass index, FMI; and body mass index, BMI) in Mexican patients with prediabetes, overweight, and obesity. Materials and Methods: This is an observational, transversal analytic study in 135 patients of both genders between 20 and 65 years of age, BMI 25.0–34.9, with diagnosis of prediabetes. The Quantose™ IR test was performed as well as anthropometric measurements (FM, FMI, and BMI) using BIA taken with Inbody 230TM. Pearson’s correlations and independent sample t-tests were estimated with a significance level of p < 0.05. Results: 135 patients were studied; 77% were female, aged 46 years in average. The prevalence of insulin resistance by Quantose™ IR was 71.1%. A positive correlation was confirmed between Quantose™ IR and FM, FMI, and BMI (p < 0.05). Patients with altered Quantose™ IR had higher FM, FMI, and BMI (p < 0.05). Conclusion: The data here presented confirm the existence of a positive and statistically significant correlation between Quantose™ IR and anthropometric measurements using BIA. This information may be useful for diagnosis and treatment in prediabetic, overweight, and obese patients.

MO099: Elastography in the Assessment of Chronic Kidney Disease: A Meta-Analysis

Abstract BACKGROUND AND AIMS We require an imagistic quantitative technique for the diagnosis and assessment of chronic kidney disease (CKD). Renal elastography has been widely used in the last years in different studies; however, the results across them are not consistent and, as a result, we conducted a meta-analysis of the published literature on this topic. METHOD The databases of PubMed, Medscape and Medline were searched for all studies published in English from 2010 until November 2021 that evaluated kidney shear wave speed (KSWS) by elastography in patients with CKD. Trial design, methodological information, patient characteristics, interventions, results and outcome data were all collected from each study according to a set protocol. RESULTS We found 33 publications, yet only 18 studies that utilized point shear wave elastography (Virtual Touch Quantification—VTQ system) were compared because the values achieved using different types of elastography are not evaluable. Finally, 1995 attendees (1241 patients with CKD versus 781 healthy subjects as the control group) were included. When comparing mean values of KSWS between studies, we found increased heterogeneity Q = 513.133; DF = 10; P < .001, I2 (inconsistency) = 98.12% (95% CI for I2 97.52–98.57%). With a standardized mean difference of –0.216, patients with CKD have a lower KSWS than healthy controls. A positive association between KSWS and eGFR was also discovered across the presented studies, with a pooled correlation coefficient of 0.38 (Z = 10.3, P < .001), Q = 73.3, DF = 5, P < .001, I2 = 93.18% (95% CI for I2 87.86–96.18). The pooled area under the ROC curve for KSWS to predict mild renal disease was 0.831 (95% CI, P < .001), Q = 28.32, DF = 6, P = .0001, I2 = 78.8% (95% CI for I2 56.37–89.72). In the four articles that used the Elast-PQ method, the data presented were insufficient for statistical analysis: area under the curve values are used to compare distinct characteristics (differentiating KSWS between mildly and moderately impaired kidneys, between non-diabetic, prediabetic and diabetic patients, or KSWS between CKD and control group), therefore not being suitable for further evaluation. CONCLUSION The results show that patients with CKD have a lower KSWS than healthy controls. It remains a viable method for monitoring the progression of CKD but because the number of studies involving renal elastography that have been published is limited and show an increased heterogeneity more research is needed to determine which factors actually influence KSWS in CKD patients and, as a result, to specify the role and indication of renal elastography in clinical practice.

Identified lncRNAs functional modules and genes in prediabetes with hypertriglyceridemia by weighted gene co-expression network analysis

BackgroundHypertriglyceridemia (HTG) is one of the most important comorbidities in abnormal glucose patients. The aim of this study was to identify lncRNAs functional modules and hub genes related to triglyceride (TG) in prediabetes.MethodsThe study included 12 prediabetic patients: 6 participants with HTG and 6 participants with normal triglyceride (NTG). Whole peripheral blood RNA sequencing was performed for these samples to establish a lncRNA library. WGCNA, KEGG pathways analysis and the PPI network were used to construct co‐expression network, to obtain modules related to blood glucose, and to detect key lncRNAs. Meanwhile, GEO database and qRT-PCR were used to validate above key lncRNAs.ResultsWe found out that the TCONS_00334653 and PVT1, whose target mRNA are MYC and HIST1H2BM, were downregulating in the prediabetes with HTG. Moreover, both of TCONS_00334653 and PVT1 were validated in the GEO database and qRT-PCR.ConclusionsTherefore, the TCONS_00334653 and PVT1 were detected the key lncRNAs for the prediabetes with HTG, which might be a potential therapeutic or diagnostic target for the treatment of prediabetes with HTG according to the results of validation in the GEO database, qRT-PCR and ROC curves.

Wavelet Based Machine Learning Approaches Towards Precision Medicine in Diabetes Mellitus

It is estimated that 422 million people around the world have diabetes mellitus (DM)—a devastating, complex, and highly heterogeneous disease—requesting better interventions based on disease subtyping. In this research, we utilize the discrete wavelet transform (DWT) to decompose and denoise DM data. Using DWT, we enhance heart rate variability (HRV) based DM diagnosis, data visualization of the disparities in Human Microbiome Project (HMP) data (gut bacteria, metabolomics, proteomics, RNA sequencing, targeted proteomics, and transcriptomics data) using demographic features, and insulin resistance prediction. We also attempt to forecast continuous glucose monitoring (CGM) ahead by 90 minutes because CGM is unable to provide real‐time blood glucose measurements. We achieve 91.9% diagnosis accuracy for Type 1 DM using Random Forest on data transformed with DWT, holding the potential for usage in clinics. In addition, our DWT‐based t‐SNE and UMAP explorative analysis of HMP data support subtypes of prediabetic patients stratified by sex, race, and age. Moreover, DWT‐based transformations provide multi‐view clustering that any other methods would not provide on metabolomics, proteomics, RNA sequencing, targeted proteomics, and transcriptomics data and outperform those without DWT. Taken together, DWT‐based machine learning approaches enable a fine resolution of subtyping DM towards precision medicine.

A HOSPITAL BASED STUDY IN TERTIARY CARE CENTRE IN NORTH INDIA: PREVALENCE OF NAFLD IN PATIENTS OF PREDIABETES AND DIABETES

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries and now becoming in developing countries also. Central Obesity and sedentary life style is usually associated with NAFLD.There are a lot of study has been done regarding prevalence of NAFLD in diabetes but lesser study available for prediabetes. In different studies reviewed by us, prevalence of NAFLD in diabetic subjects has been reported to range from 26.5% to 86.7%1,2,3. In prediabetic patients this prevalence has been seen to range from 48.24% to 68%4,5,6. OBJECTIVE: To assess the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in prediabetes and diabetes patients. RESEARCH DESIGN AND METHODS: A cross sectional study was conducted at SRN Hospital, Prayagraj. A total of 100 prediabetic and 100 diabetic patients were enrolled in the study. Patients on the basis of HbA1c(glycated hemoglobin) are divided in to two groups, prediabetic and diabetic group. Patients with known case of liver disease, taking steroid and regular alcohol intake were excluded from study. Ultrasonography B mode used for detection of fatty liver inltration and their grading. RESULT: Prevalence of NAFLD was 48% in prediabetic and 54% in diabetic group. In prediabetic group, 32% had grade 1, 13% had grade 2 and 3% had grade 3 NAFLD whereas in diabetic group 34% had grade 1, 18% had grade 2 and 2% had grade 3 NAFLD. In the present study, we found that diabetic patients as compared to pre-diabetic patients were signicantly older, had a higher proportion of males and higher BMI(Body mass index). Conclusion: There was no signicant difference between two groups for association of NAFLD and its severity. Higher BMI is associated with higher chances to get NAFLD and diabetes mellitus in future.

Effects of Leisure-Time Physical Activity on Cognitive Reserve Biomarkers and Leisure Motivation in the Pre-Diabetes Elderly.

The purpose of this study was to investigate the change in cognitive reserve biomarkers of the pre-diabetic individual according to the types of leisure-time physical activity (aerobic or resistance physical activity). The research subjects (n = 184) who participated in the survey were pre-diabetic and diabetic patients who were visiting university hospitals and welfare centers. The intervention subjects (n = 36) who were elderly females with pre-diabetes volunteered to participate in the study by performing regular physical exercise (aerobic or resistance exercise). The study participants were 65 years of age or older with pre-diabetes defined by a glycated hemoglobin (HbA1c) level of (5.7–6.4)%. All research subjects performed motivation and stress questionnaire survey. All intervention subjects participated in leisure-time physical activity (LTPA) for 12 weeks. Body composition, HbA1c, and cognitive reserve biomarkers were measured at baseline, and at 6 and 12 weeks. LTPA motivation confirmed that the LTPA participants had a high level of motivation. Stress confirmed that the stress level of LTPA participants was low. Two-way within-factor ANOVA revealed significant group × time interaction for weight (p < 0.05), BMI (p < 0.01), % fat (p < 0.001), SBP (p < 0.05), HbA1c (p < 0.001), BDNF (p < 0.001), and Beta-Amyloid 1–42 (p < 0.001). In both physical activity groups, HbA1c (p < 0.001), NGF (p < 0.05), BDNF (p < 0.05), and Cathepsin B (p < 0.05) improved significantly at 12 weeks, compared to baseline and 6 weeks. In the resistance physical activity group, Beta-Amyloid 1–42 (p < 0.01) and Homocysteine (p < 0.05) significantly decreased at 12 weeks, compared to baseline and at 6 weeks. The LTPA showed high levels of integrated and identified regulation among leisure motive types, and the level of stress was found to be low. The LTPA is effective in reducing the HbA1c levels of the pre-diabetes elderly. In addition, the pre-diabetes elderly were found to have increased NGF, BDNF, and cathepsin B, and decreased Beta-Amyloid 1–42 and homocysteine. Regular leisure-time physical activity has a positive effect on cognitive reserve biomarkers through improving glycemic control by reducing weight and % fat in the pre-diabetes elderly.

The Effects of Freshwater Clam (Corbicula fluminea) Extract on Serum Tumor Necrosis Factor-Alpha (TNF-α) in Prediabetic Patients in Taiwan.

Freshwater clam extract (FCE) is a functional food that regulates the immune system and has been demonstrated in numerous studies to display desirable anti–tumor necrosis factor-alpha (TNF-α) responses. In addition, excess TNF-α production is positively associated with type 2 diabetes. However, few longitudinal clinical studies evaluating the efficiency and toxicity of FCE are available. This article reports that patients with prediabetes who received FCE had a desirable outcome of a reduction in serum TNF-α for a long period. This was a double-blind, randomized, parallel clinical trial conducted using FCE intervention and placebo groups, and 36 patients with prediabetes were enrolled. Two grams of FCE or placebo was consumed daily for 180 consecutive days. The serum of the participants was collected at four time points (0M: before the intervention; 3M: after 3 months of intervention; 6M: after 6 months of intervention; 12M: 6 months after cessation of intervention at 6M). A serum TNF-α concentration higher than 4.05 pg/mL was defined as a cut-off value. FCE reduced serum TNF-α in all participants at 6M and 12M. Moreover, FCE significantly suppressed serum TNF-α concentrations at 6M and 12M and inhibited TNF-α release with time series in subjects with elevated TNF-α values. FCE intervention effectively reduced serum TNF-α and persistently sustained the effects for half a year in patients with prediabetes. Gas chromatography–mass spectrometry (GS-MS) analysis revealed that the major components of FCE were phytosterols and fatty acids, which exerted anti-inflammatory and anti-TNF-α abilities. Hence, FCE has the potential to be developed as a natural treatment for prediabetic patients in Taiwan.