Glycemic Measures Research Articles

Branched-Chain and Aromatic Amino Acids, Type 2 Diabetes, and Cardiometabolic Risk Factors among Puerto Rican Adults.

(1) Background: Branched-chain and aromatic amino acids (BCAAs/AAAs) have been considered as markers of type 2 diabetes (T2D); however, studies on associations between these metabolites and T2D and cardiometabolic traits in Hispanic populations are limited. The aim of this study was to examine the associations between baseline BCAAs (isoleucine, leucine, valine)/AAAs (phenylalanine, tyrosine) and prevalent and incident T2D, as well as baseline and longitudinal (2 year) changes in cardiometabolic traits (measures of glycemia, dyslipidemia, inflammation, and obesity) in two large cohorts of adults of Puerto Rican descent. (2) Methods: We included participants of the Boston Puerto Rican Health Study (BPRHS, n = 670) and San Juan Overweight Adult Longitudinal study (SOALS, n = 999) with available baseline metabolite and covariate data. T2D diagnosis was defined based on American Diabetes Association criteria. Multivariable logistic (for baseline T2D), Poisson (for incident T2D), and linear (for cardiometabolic traits) regression models were used; cohort-specific results were combined in the meta-analysis and adjusted for multiple comparisons. (3) Results: Higher baseline BCAAs were associated with higher odds of prevalent T2D (OR1SD BCAA score = 1.46, 95% CI: 1.34-1.59, p < 0.0001) and higher risk of incident T2D (IRR1SD BCAA score = 1.24, 95% CI: 1.13-1.37, p < 0.0001). In multivariable longitudinal analysis, higher leucine and valine concentrations were associated with 2-year increase in insulin (beta 1SD leucine = 0.37 mcU/mL, 95% CI: 0.11-0.63, p < 0.05; beta 1SD valine = 0.43 mcU/mL, 95% CI: 0.17-0.68, p < 0.01). Tyrosine was a significant predictor of incident T2D (IRR = 1.31, 95% CI: 1.09-1.58, p < 0.05), as well as 2 year increases in HOMA-IR (beta 1SD tyrosine = 0.13, 95% CI: 0.04-0.22, p < 0.05) and insulin concentrations (beta 1SD tyrosine = 0.37 mcU/mL, 95% CI: 0.12-0.61, p < 0.05). (4) Conclusions: Our results confirmed the associations between BCAAs and prevalent and incident T2D, as well as concurrent measures of glycemia, dyslipidemia, and obesity, previously reported in predominantly White and Asian populations. Baseline leucine, valine, and tyrosine were predictors of 2 year increases in insulin, whereas tyrosine was a significant predictor of deteriorating insulin resistance over time. Our study suggests that BCAAs and tyrosine could serve as early markers of future glycemic changes in Puerto Ricans.

Glycated Hemoglobin A1c Time in Range and Dementia in Older Adults With Diabetes

Individuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence. To examine the association between HbA1c TIR and incidence of ADRD in older veterans with diabetes. The study sample for this cohort study was obtained from administrative and health care utilization data from the Veterans Health Administration and Medicare from January 1, 2004, to December 31, 2018. Veterans 65 years or older with diabetes were assessed. Participants were required to have at least 4 HbA1c tests during the 3-year baseline period, which could start between January 1, 2005, and December 31, 2014. Data analysis was conducted between July and December 2023. Hemoglobin A1c TIR was calculated as the percentage of days during baseline in which HbA1c was in individualized target ranges based on clinical characteristics and life expectancy, with higher HbA1c TIR viewed as more favorable. The association between HbA1c TIR and ADRD incidence was estimated. Additional models considered ADRD incidence in participants who were above or below HbA1c target ranges most of the time. The study included 374 021 veterans with diabetes (mean [SD] age, 73.2 [5.8] years; 369 059 [99%] male). During follow-up of up to 10 years, 41 424 (11%) developed ADRD. Adjusted Cox proportional hazards regression models showed that lower HbA1c TIR was associated with increased risk of incident ADRD (HbA1c TIR of 0 to <20% compared with ≥80%: hazard ratio, 1.19; 95% CI, 1.16-1.23). Furthermore, the direction of out-of-range HbA1c levels was associated with incident ADRD. Having greater time below range (≥60%, compared with ≥60% TIR) was associated with significantly increased risk (hazard ratio, 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (ie, insulin and sulfonylureas) or with hypoglycemia events. In this study of older adults with diabetes, increased HbA1c stability within patient-specific target ranges was associated with a lower risk of ADRD. Lower HbA1c TIR may identify patients at increased risk of ADRD.

Testosterone in prevention and treatment of type 2 diabetes in men: Focus on recent randomized controlled trials.

In epidemiological studies, lowered serum testosterone concentrations are common in men with obesity, prediabetes, and established type 2 diabetes (T2D). In men with prediabetes, lowered serum testosterone also predicts a future risk of T2D in men. Administration of testosterone consistently reduces fat mass and increases skeletal muscle mass-body compositional changes expected to be metabolically favorable. In men with established T2D, the effects of testosterone treatment on glycemic measures are inconsistent. Irrespective of baseline serum testosterone concentration in men with prediabetes or newly diagnosed early-onset T2D, testosterone treatment prescribed in conjunction with a lifestyle program has been reported to reduce the risk of T2D by 40% after 2 years, suggesting that either a lifestyle program is required to facilitate the glycemic benefit of testosterone treatment and/or that testosterone treatment has more favorable effects on glycemia in men early in the evolution or onset of the disease. The durability of the benefit and longer-term safety of testosterone treatment have not been established. Therefore, more studies are required before testosterone treatment can be recommended for the prevention and/or treatment of men with or at elevated risk of T2D who do not have hypogonadism due to an established disease of the hypothalamic-pituitary-testicular axis.

Facilitating the Virtual Exercise Games for Youth with T1D (ExerT1D) Peer Intervention: Protocol Development and Feasibility.

Barriers to moderate-to-vigorous physical activity (MVPA) for adolescents with type 1 diabetes (T1D) include physiology, transition to autonomy, and diabetes-specific stigma. Opportunities for T1D peer activities with T1D role model support are limited. To address this need, our single-arm pilot study tested the Home-based Virtual Activity Program for Youth with T1D (HAP-V-T1D) for feasibility. Participants (n=15) were mean age 15.6 [SD 1.5] years, 7 non-Hispanic white, 6 female, 2 non-binary, mean A1c 8.9%±2.2%. The program included an MVPA videogame, physician-led education regarding managing T1D around MVPA, objective habitual MVPA goal-setting , and T1D management skills guided by young adult instructors living with T1D. For feasibility, 13/15 participants attended 10/12 sessions. Participants' perceptions of the program, comfort, instructors, and group cohesion were rated high/very high (4.2±0.5 to 4.8±0.3 out of 5).Motivation for the videogame was also high (4.1±0.4 out of 5). Instructor-adolescent interactions related to building T1D management skills were rated as excellent for 78% of sessions. Similarly, sharing knowledge and experiences were rated as excellent for 68% of sessions. However, adolescent-adolescent interactions were poor (communication 29% excellent, peer interactions 8% excellent). The most reported barriers to participation were negative mood and oversleeping. No participants experienced diabetic ketoacidosis, severe hypoglycemia, or injuries during the study period. Compared to baseline, glycemic metrics appeared to decrease during and post intervention (d= -0.72, -1.12). HAP-V-T1D facilitated unprecedented T1D peer support achievements by engaging diverse youth with T1D in an MVPA program led by T1D role models. Larger studies are needed to assess if this intervention can improve glycemic measures and reduce diabetes-specific stigma.

Metabolite Profiles of Plant-Based Diets and Cardiometabolic Risk in the Mediators of Atherosclerosis in South Asians Living in America Study

BackgroundHealthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk. ObjectivesThis study aimed to identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D. MethodsWe included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultraperformance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index, and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable-adjusted linear and logistic regressions. ResultsMetabolite profiles for PDI, hPDI, and uPDI consisted of n = 51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower low density lipoprotein cholesterol and high density lipoprotein cholesterol. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin, lower odds of overweight (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.51, 0.81) and obesity (OR: 0.59; 95% CI: 0.48, 0.74), and lower odds of incident T2D (OR: 0.66; 95% CI: 0.45, 0.97). ConclusionsMetabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.

1246-P: Maternal Proinflammatory Markers Associate with Obesity and Glycemic Measures in Pregnancy

1246-P: Maternal Proinflammatory Markers Associate with Obesity and Glycemic Measures in Pregnancy

Prospective cohort studies underscore the association of abnormal glycemic measures with all-cause and cause-specific mortalities

The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6mmol/L, HbA1c ≥ 5.7%, TyG index <8.31 or ≥9.08 increased the risks of all-cause, CVD-related, and cancer-related mortalities in the UKB cohort. FPG or HbA1c increased the discrimination of the conventional risk model in predicting all-cause and CVD-related mortalities in both cohorts. Thus, increased levels of FPG and HbA1c and U-shaped TyG index increase the risks of all-cause especially CVD-related mortalities.

Hyperglycemia as a predictor of mortality in adult patients with COVID-19 hospitalized in a public hospital in Peru

ObjectiveTo investigate the association between glycemic levels and mortality in patients without diabetes hospitalized for COVID-19 in Perú. MethodsIn a retrospective study conducted from April to June 2020 in Cayetano Heredia hospital, 529 patients were admitted with a positive SARS-CoV-2 laboratory result or a computed tomography chest scan with suggestive images of COVID-19 pneumonia. Patients were classified into three groups according to their first blood glucose measure. Group 1: glucose level lower than 100 mg/dL; Group 2: glucose level between 100 mg/dL and 126 mg/dL, and Group 3: glucose level over 126 mg/dL. Demographical characteristics, concomitant diseases, laboratory data, and treatment received during hospitalization were also described. Regression-adjusted models were used to analyze association of interest. ResultsThe number of patients who met inclusion criteria was 289. Mortality occurred in 137 cases (47 %). Group 1, group 2 and group 3 had 29/77 (38 %), 58/120 (48 %), and 50/92 (54 %) mortality/severe cases, respectively. After all available confounding factors were adjusted, the group of patients with blood glucose levels over 126 mg/dL had a 73 % increased mortality hazard compared to the ones lower than 100 mg/dL (aHR: 1.73 [95%CI: 1.05–2.84]; p = 0.032). ConclusionHyperglycemia (≥ 126 mg/dL) at baseline in patients without a previous history of diabetes is associated with mortality in admitted patients with COVID-19. Routine laboratory testing should never miss a baseline measure of glycemia as this allows for timely blood glucose management, thereby minimizing its negative impact on COVID-19 patients' outcomes.

Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women

Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited. To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction. This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023. Mediterranean diet score (range, 0-9) was computed based on 9 dietary components. Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association. Among 25 315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24 036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend < .001). Further adjusting for lifestyle factors attenuated the risk reductions, but they remained statistically significant (middle adherence group: HR, 0.92 [95% CI, 0.85-0.99]; upper adherence group: HR, 0.89 [95% CI, 0.82-0.98]; P for trend = .001). Of the biomarkers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk (explaining 14.8% and 13.0%, respectively, of the association), followed by triglyceride-rich lipoproteins (10.2%), body mass index (10.2%), and insulin resistance (7.4%). Other pathways, including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension, had smaller contributions (<3%). In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors.

Real-Life Achievements of MiniMed 780G Advanced Closed-Loop System in Youth with Type 1 Diabetes: AWeSoMe Study Group Multicenter Prospective Trial.

Background: We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. Methods: This prospective observational multicenter study collected demographic, clinical, and 2-week 780G system data at five time points. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. Results: The cohort included 93 children, 43% girls, with a median age of 15.1 years (interquartile range [IQR] 12.9,17.0). A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime < 0.001) after the transition to 780G. The mean hemoglobin A1c (HbA1c) (SE) was 8.65% (0.12) at baseline and dropped by >1% after 1 year to 7.54% (0.14) (ptime < 0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (P < 0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (P = 0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (P < 0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to Advanced Hybrid Closed-Loop (AHCL) usage were predictors of achieving optimal glycemic control. Conclusions: The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of health care professionals, youth, and caregivers.

Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Do fructosamine-3-kinase genetic polymorphisms explain the discordance between HbA1c and other measures of glycaemia?

Do fructosamine-3-kinase genetic polymorphisms explain the discordance between HbA1c and other measures of glycaemia?

Association Between Triglyceride-Glucose Index and Homeostasis Model Assessment for Insulin Resistance with Estimated Glucose Disposal Rate.

This cross-sectional study was aimed to compare insulin resistance, Triglyceride- Glucose (TyG) index, fatty liver index (FLI) and hepatic steatosis index (HSI), glycaemic and lipids among groups/quartiles based upon estimated Glucose Disposal Rate (eGDR) from August 2022 to December 2022 among 249 male participants. The eGDR results in (mg/kg/min) were divided into four quartiles as: Group-I: {<6.88, n = 62}, Group-II: {<6.88-9.45, n = 63}, Group-III: {9.46-10.39, n = 62}, and Group-IV: {>10.39, n = 62}. Fasting plasma glucose (FPG), HbA1c, low density lipoprotein (LDL), homeostasis model assessment for insulin-resistance (HOMAIR), and TyG index demonstrated significant worsening increase from high to low eGDR groups. Receiver operating curve (ROC) analysis to calculate area under curve (AUC) for diagnostic efficiency candidate indices for eGDR demonstrated highest AUC for FLI as AUC: 0.736 (95% CI: 0.669-0.803), p < 0.001, followed by FPG: AUC: 0.682 (95% CI: 0.606-0.757), HOMAIR: AUC: 0.670 (95% CI: 0.602-0.739), HSI: AUC: 0.660 (95% CI: 0.589-0.731), TyG index: 0.658 (95% CI: 0.583-0.732), and HbA1c: 0.639 (95% CI: 0.583-0.732). Glycaemic measures, lipid indices, insulin resistance and TyG index deteriorated with declining eGDR. Diagnostic performance as evaluated by AUC for eGDR was highest for FLI, followed by FPG, HOMAIR, HSI, TyG index, HbA1c, and triglycerides. Key Words: Triglyceride, Insulin, Glucose, Diabetes.

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368). Clinical research unit. Adults with obesity and prediabetes or diet-controlled diabetes. Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, -1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. Small, single-site study; baseline differences in weight by group. In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. American Heart Association.

Add-on Vitamin E in Improving Treatment Outcomes in Diabetic Peripheral Neuropathy: A Prospective Interventional Study

Background: Neuropathy is one of the most common long-standing complications of diabetes, affecting over 50% of the diabetic individuals. Managing DPN and its complications involves comprehensive care and a multidisciplinary approach. Besides pharmacological treatments, botanicals and dietary supplements that have also been found to improve symptoms of DPN without affecting glucose control. The possible role of vitamin E in the management of DPN have been postulated in various studies. The present study thus aimed to prospectively assess whether add-on treatment with vitamin E can improve treatment outcomes in diabetic peripheral neuropathy.Methods: The study included newly diagnosed patients with diabetic peripheral neuropathy for a period of initial two months. Patients were randomly allocated to either standard treatment Group (Group A) or the interventionGroup (Group B). As a part of intervention, patients received vitamin E 400mg once daily in addition to thestandard of care. Efficacy Parameters measured at baseline, 6 months and 12 months included changes in visual analog scoring, mean pain score, brief pain inventory and patient’s global impression of change. Treatment safety, quality of life and treatment adherence was assessed. Data was statistically analysed.Result: The study included a total of 100 patients, 50 patients in each Group. Significantly higher decrease of glycaemic measures was noted for Group B compared to Group A in terms of PPPG and serum creatinine, however, there was comparable change in HbA1c and FPG for both Groups. There was comparable significant reduction in mean VAS scoring at 6 and 12 months for Group B. Considering all the efficacy measures, there was highest reduction for the pain interference in the intervention arm (Group B), in comparison to Group A. (p&lt;0.001). Quality of life measures and mean adherence scoring significantly increased for treatment group B as compared to A at both 6 months and 12 months of study assessments. No major safety concerns were reported during the study period.Conclusion: Our study noted that addition of vitamin E as an added supplementation to the standard of careshowed benefits in terms of patient reported reduced pain interference and pain perception, which also significantly improved overall quality of life in these patients.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM). We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up. A minimum of two studies evaluating the same intervention-outcome combination were needed to conduct meta-analyses, otherwise studies were described narratively. Meta-regression was used to evaluate whether associations varied by additional variables. We assessed risk of bias using the Critical Appraisal Skills Programme checklist. PROSPERO record CRD42018102380. We included 31 studies in the review with a total sample size of 8624 participants, and 26 studies in meta-analyses. Two-thirds of studies followed up participants at 1 year or less. Pharmacological interventions were associated with reduced risk of T2DM (0.80 [95% CI 0.64-1.00], n = 6 studies), as were lifestyle interventions albeit with a smaller effect size (0.88 [95% CI 0.76-1.01], n = 12 studies). Dietary and physical activity interventions were associated with a small reduction in fasting plasma glucose, particularly in longer interventions, but inconsistent effects were seen for other continuous outcomes. Although possibly due to chance, interventions to reduce hyperglycaemia after GDM may be effective. Future research should improve understanding of how interventions affect glucose control and how to optimise interventions for this population.

Association of Gut Microbiota-Related Metabolites and Type 2 Diabetes in Two Puerto Rican Cohorts.

(1) Aims: Gut microbiota metabolites may play integral roles in human metabolism and disease progression. However, evidence for associations between metabolites and cardiometabolic risk factors is sparse, especially in high-risk Hispanic populations. We aimed to evaluate the cross-sectional and longitudinal relationships between gut microbiota related metabolites and measures of glycemia, dyslipidemia, adiposity, and incident type 2 diabetes in two Hispanic observational cohorts. (2) Methods: We included data from 670 participants of the Boston Puerto Rican Health Study (BPRHS) and 999 participants of the San Juan Overweight Adult Longitudinal Study (SOALS). Questionnaires and clinical examinations were conducted over 3 years of follow-up for SOALS and 6 years of follow-up for BPRHS. Plasma metabolites, including L-carnitine, betaine, choline, and trimethylamine N-oxide (TMAO), were measured at baseline in both studies. We used multivariable linear models to evaluate the associations between metabolites and cardiometabolic risk factors and multivariable logistic and Poisson regressions to assess associations with prevalent and incident type 2 diabetes, adjusted for potential confounding factors. Cohort-specific analyses were combined using a fixed-effects meta-analysis. (3) Results: Higher plasma betaine was prospectively associated with lower fasting glucose [-0.97 mg/dL (95% CI: -1.59, -0.34), p = 0.002], lower HbA1c [-0.02% (95% CI: -0.04, -0.01), p = 0.01], lower HOMA-IR [-0.14 (95% CI: -0.23, -0.05), p = 0.003], and lower fasting insulin [-0.27 mcU/mL (95% CI: -0.51, -0.03), p = 0.02]. Betaine was also associated with a 22% lower incidence of type 2 diabetes (IRR: 0.78, 95% CI: 0.65, 0.95). L-carnitine was associated with lower fasting glucose [-0.68 mg/dL (95% CI: -1.29, -0.07), p = 0.03] and lower HbA1c at follow-up [-0.03% (95% CI: -0.05, -0.01), p < 0.001], while TMAO was associated with higher fasting glucose [0.83 mg/dL (95% CI: 0.22, 1.44), p = 0.01] and higher triglycerides [3.52 mg/dL (95% CI: 1.83, 5.20), p < 0.0001]. Neither choline nor TMAO were associated with incident type 2 diabetes. (4) Conclusions: Higher plasma betaine showed consistent associations with a lower risk of glycemia, insulinemia, and type 2 diabetes. However, TMAO, a metabolite of betaine, was associated with higher glucose and lipid concentrations. These observations demonstrate the importance of gut microbiota metabolites for human cardiometabolic health.

Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy. We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol. Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo. Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy. British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.

Discrete glucose profiles identified using continuous glucose monitoring data and their association with adverse pregnancy outcomes

Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited. This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes. This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity. Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09). Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia.

Abstract P475: Adherence to the EAT-Lancet Planetary Health Diet and Cardiometabolic Risk Markers in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study

Introduction: Poor diet is among the top risk factors for cardiometabolic disease, which disproportionately burdens South Asians. In 2019, the EAT-Lancet Commission proposed a Planetary Health Diet (PHD) designed to optimize human and global environmental health. Objective: We examined associations between a novel Planetary Health Diet Index (PHDI), that reflects adherence to the EAT-Lancet recommendations, and cardiometabolic risk in a prospective cohort of South Asians in the US. Methods: We included participants from the MASALA study with complete baseline (n=891) and 5-year follow-up (n=735) examinations. The PHDI was comprised of 15 food components with scoring based on the ranges prescribed by the EAT-Lancet commission for a total score range of 0–140. Higher scores indicate greater adherence to the PHDI. We used multivariable linear and logistic regression models to examine cross-sectional and prospective (5-years) associations between baseline PHDI and measures of glycemia, blood lipids, inflammation, and adiposity, adjusting for demographic, health, lifestyle, and baseline value of biomarker (for prospective models). Logistic regression was used to examine association between baseline PHDI and incident type 2 diabetes (among n=661 participants free from diabetes at baseline) Results: Among MASALA study participants (49% female, mean age 57 y), the mean PHDI score was 88.8 (SD 9.47). At baseline, each 10 unit increase in PHDI scores were associated with (β ± SE) lower fasting glucose (-0.5±0.24 mmol/L), HbA1c (-0.49±0.22%), LDL cholesterol (-0.015±0.007 mmol/L), CRP (-5.87±2.35 mg/L), higher adiponectin (4.71 ±2.01 mg/dL), lower body weight (-0.59 ±0.26 kg), BMI (-0.27±0.11 kg/m 2 ), waist circumference (-0.82±0.29 cm), visceral fat (-3.22±1.32 cm 2 ), and pericardial fat (-0.92±0.43 cm 3 ) ( p &lt;0.05 for all). Higher PHDI scores were associated lower odds of obesity [OR (95% CI): 0.80 (0.71-0.92] and overweight [0.77 (0.74-0.85)]. Prospectively, higher PHDI scores were associated with lower fasting glucose (-0.28 ± 0.14 mmol/L), lower HbA1c (-0.08±0.03%), higher HDL (0.38±0.17 mmol/L), lower body weight (-0.37±0.12 kg), BMI (-0.08±0.03 kg/m 2 ), waist circumference (-0.49±0.17 cm), and systolic blood pressure (-0.65 ± 0.30 mmHg) ( p &lt;0.05 for all). Each 10-unit higher PHDI was associated with a 20% lower risk of incident diabetes [OR (95%CI): 0.80 (0.54-0.86)]. Conclusions: In the MASALA study, we found that greater adherence to the PHDI was associated with better cardiometabolic risk factors and lower risk of incident type 2 diabetes. These observations support the planetary health diet as a feasible strategy to address planetary health while optimizing human health outcomes.