Lower HbA1c Research Articles

The impact of Serum Amylin on Body mass index in Children with type1 Diabetes Mellitus newly diagnosis

Background: Pancreatic β cells' inability to synthesize insulin is the defining feature of type 1 diabetes mellitus (T1DM), an endocrine illness. This action involves the peptide hormone amylin, which is co-secreted with insulin and plays a key role in controlling glucose homeostasis and appetite. It also influences body weight, calorie intake, stomach emptying, glucagon release suppression, and satiety. Subjects, Material, and Method: This study included 120 pediatric individuals aged between( 2-14) years. They were divided into four groups. Group one contains 40 lean patients with T1DM, with a BMI≥85 percentile, and group two contains 40 underweight patients with (T1DM) with a BMI≥5 percentile. The Group contains 40 healthy pediatrics and ages matched with the patients subdivided into (group three, lean control with a BMI less than 85 percentile. The group numbered 22, and four groups, underweight control with BMI≥5 percentile, consisted of 18 pediatric underweight healthy as controls. They were analyzed for fasting serum glucose, amylin, and HbA1c. Results: The levels of Amylin in the control group(lean and underweight) were higher than in the patients with diabetes mellitus(lean and underweight). Also, fast blood glucose( FBG) was found in the Lean DM group. Similarly, the Underweight DM group was higher than those observed in the Lean Control and Underweight Control groups. For HbA1c%, the Lean DM group. The Underweight DM group exhibited a higher mean HbA1c%. In contrast, the Lean Control and Underweight Control groups had significantly lower mean HbA1c% values. Conclusion: The control group had higher Amylin levels, a potential biomarker for metabolic status in children with T1DM, and could inform therapeutic strategies to optimize glycemic control and body weight management. In comparison, the patient group had higher FBG values. The Lean DM group had higher HbA1c% values, while the Underweight DM group had slightly higher values. Both control groups had significantly lower HbA1c% values.

A comprehensive lifestyle index and its associations with DNA methylation and type 2 diabetes among Ghanaian adults: the rodam study

BackgroundA series of modifiable lifestyle factors, such as diet quality, physical activity, alcohol intake, and smoking, may drive the rising burden of type 2 diabetes (T2DM) among sub-Saharan Africans globally. It is unclear whether epigenetic changes play a mediatory role in the associations between these lifestyle factors and T2DM. We assessed the associations between a comprehensive lifestyle index, DNA methylation and T2DM among Ghanaian adults.MethodsWe used whole-blood Illumina 450 k DNA methylation data from 713 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. We constructed a comprehensive lifestyle index based on established cut-offs for diet quality, physical activity, alcohol intake, and smoking status. In the T2DM-free discovery cohort (n = 457), linear models were fitted to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) associated with the lifestyle index after adjustment for age, sex, body mass index (BMI), and technical covariates. Associations between the identified DMPs and the primary outcome (T2DM), as well as secondary outcomes (fasting blood glucose (FBG) and HbA1c), were determined via logistic and linear regression models, respectively.ResultsIn the present study population (mean age: 52 ± 10 years; male: 42.6%), the comprehensive lifestyle index showed a significant association with one DMP annotated to an intergenic region on chromosome 7 (false discovery rate (FDR) = 0.024). Others were annotated to ADCY7, SMARCE1, AHRR, LOXL2, and PTBP1 genes. One DMR was identified and annotated to the GFPT2 gene (familywise error rate (FWER) from bumphunter bootstrap = 0.036). None of the DMPs showed significant associations with T2DM; directions of effect were positive for the DMP in the AHRR and inverse for all the other DMPs. Higher methylation of the ADCY7 DMP was associated with higher FBG (p = 0.024); LOXL2 DMP was associated with lower FBG (p = 0.023) and HbA1c (p = 0.049); and PTBP1 DMP was associated with lower HbA1c (p = 0.002).ConclusionsIn this explorative epigenome-wide association study among Ghanaians, we identified one DMP and DMR associated with a comprehensive lifestyle index not previously associated with individual lifestyle factors. Based on our findings, we infer that lifestyle factors in combination, affect DNA methylation, thereby influencing the risk of T2DM among Ghanaian adults living in different contexts.

Chronic kidney disease in Kuwait: a multicenter study of two cohorts with different levels of access to public healthcare

IntroductionKuwait has a large expatriate community who experience both restricted access to public health services and lower income than Kuwaiti citizens. Given these conditions, we examined differences in characteristics and management of chronic kidney disease (CKD) between Kuwaitis and expatriates.MethodsClinical and laboratory data for adult CKD Stages 3–5 not on dialysis (CKD 3–5 ND) patients with native kidneys attending nephrology clinics in all Ministry of Health hospitals collected from January 1, 2022, to December 31, 2022. Cohort was then divided into Kuwaiti patients and expatriates patients for comparison.ResultsWe collected data from 2,610 patients (eGFR: 30.8 ml/min/1.73m2; age: 62.6 years; males: 56.7%; Kuwaitis: 62.1%). Kuwaitis were older (63.94 vs. 60.3 years, p < 0.001), with lower mean eGFR (30.4 vs. 31.5 ml/min/1.73m2, p = 0.052) than non-Kuwaitis, however, Kuwaitis had lower mean blood pressure (137.2/76.5 vs. 139.1/78.9 mmHg, p = 0.006), lower HbA1c in diabetics (7.59 vs. 7.82%, p = 0.010), and better lipid profile despite higher body mass indexes (29.6 vs. 28.9 kg/m2, p = 0.002). Both groups had high diabetes mellitus and hypertension rates. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were used in only 22.6% and renin-angiotensin-aldosterone system inhibitors (RAASi) in only 46.2%.ConclusionCKD 3–5 ND is caused by diabetes mellitus in 56.6% of cases, and the majority have hypertension. In our study, non-Kuwaitis had higher eGFR; however, restricted public healthcare access and lower income can lead to an unhealthy diet and suboptimal care, which may cause higher blood pressure, higher HbA1c, and a higher dyslipidemia rate. RAASi and SGLT2i utilization must increase to combat CKD, and antihypertensive selection must improve.

Genetic architecture of routinely acquired blood tests in a British South Asian cohort

Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

Impact of Continuous Glucose Monitoring on Hemoglobin A1c and Height Trends in Latin American Children with Type 1 Diabetes Onset over 3 Years: A Multicenter Study

ObjectiveTo evaluate changes in HbA1c levels and z-height over three years based on Continuous glucose monitoring (CGM) usage among children with new-onset type 1 diabetes (T1DM) from various Latin American centers. MethodsData on z-height, CGM access, and HbA1c (%) were collected for Latin American children aged six months to 18 years with T1DM onset from 19 centers in a retrospective analysis of medical records, from 2020 to 2023. A two-way ANOVA method with repeated measures and multiple regression analyses were performed. Results433 children (46.0% F) aged 8.7 ± 3.7 years were included, and 199 (45.9%) used CGM. Mean HbA1c was significantly lower in years 1, 2, and 3 than in baseline in children with CGM but not those without CGM. The z-height decreased significantly with the years in both groups. However, the CGM users showed a significantly greater height in years 2 and 3 than the non-users. Multiple linear regression analysis showed that CGM users exhibited a significantly lower incremental area under the curve (AUC) for HbA1c during follow-up than non-users. Furthermore, a lower incremental AUC for HbA1c was associated with a smaller decremental AUC for z-height (R2 = 0.19). Multiple logistic regression analysis revealed that children with CGM were 80% more likely (OR=0.22; 95% CI 0.1-0.6) to achieve an HbA1c < 7% in the third year of follow-up. ConclusionsThis study reveals a significant association between CGM use and lower HbA1c from the onset of T1DM over a three-year follow-up in Latin American children. Further prospective studies should be performed to confirm this finding.

Effects of collaborative learning-based food literacy program on healthy eating behavior and hemoglobin A1c among older adults with uncontrolled type 2 diabetes: A randomized controlled trial study in Thailand.

Uncontrolled type 2 diabetes mellitus (T2DM) is a prevalent issue among older adults. Healthy eating behavior (HEB) is a significant factor contributing to blood sugar control. It is a complex behavior that requires knowledge, attitudes, and skills in food literacy, which can be achieved through collaborative learning by nurses. Although collaborative learning has successfully improved food literacy and HEB among adults and older adults in general, its effectiveness has not been investigated among older adults with uncontrolled T2DM. This randomized controlled trial aimed to examine the effects of the Collaborative Learning-Based Food Literacy Enhancement Program (CLFLEP) on HEB and hemoglobin A1c (HbA1c) levels among older adults with uncontrolled T2DM. Participants were 80 older adults with uncontrolled T2DM attending primary care units (PCUs) or sub-district health promotion hospitals in northern Thailand. They were randomly assigned to either the experimental group (n = 40) or the control group (n = 40). The experimental group received the CLFLEP to enhance four domains of food literacy through five major elements of collaborative learning, while the control group received standard care. Data were collected between January and June 2023 using the Demographic Data Form, the Eating Behavior Questionnaire, the HbA1c test, and the Short Food Literacy Questionnaire. Data analysis involved descriptive statistics for demographic characteristics and independent t-test and paired sample t-test for HEB and HbA1c based on intention-to-treat (ITT) and per-protocol (PP) analyses. The experimental group had a higher HEB score than the control group (p <0.001 for ITT and PP) and higher than their scores before program participation (p <0.001 for ITT and PP). The effect size (Cohen's d) was 1.46. The experimental group also had a lower HbA1c level than the control group (p = 0.002 for ITT and PP) and lower than their levels before program participation (p = 0.005 for ITT and 0.001 for PP). The effect size (Cohen's d) was 0.70. The CLFLEP was effective in promoting food literacy, HEB, and blood sugar control. Nurses can be trained to use this program to provide collaborative health education for older adults with uncontrolled T2DM. Nursing administrators can use these findings to develop organizational policies that enhance nurses' competencies as educators skilled in collaborative learning. TCTR20221222005 [Thai Clinical Trials Registry].

Promising predictors of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus

BackgroundDiabetic peripheral neuropathy (DPN) in children and adolescents with type 1 diabetes mellitus (T1DM) is a growing issue, with controversial data in the terms of prevalence and evaluation timelines. Currently, there are no clear standards for its early detection. Therefore, our aim was to assess the contribution of the Michigan neuropathy screening instrument (MNSI), lipid profile, serum neuron specific enolase (NSE), and serum heat shock protein 27 (HSP 27) to the prediction of DPN in children and adolescents with T1DM.MethodsIn this case-control study, fifty children diagnosed with T1DM for at least five years were enrolled and evaluated through complete neurological examination, MNSI, and nerve conduction study (NCS). Additionally, HbA1c, lipid profile, serum NSE, and serum HSP 27 levels were measured for patients and controls.ResultsThe prevalence of DPN in our study was 24% by NCS, and electrophysiological changes showed a statistically significant lower conduction velocity for the posterior tibial and sural nerves, as well as a prolonged latency period for the common peroneal and sural nerves in neuropathic patients. In these patients, older age, earlier age of diabetes onset, longer disease duration, higher total cholesterol, triglycerides, low density lipoprotein cholesterol, HbA1c, serum NSE, and HSP27 levels were observed. The MNSI examination score ≥ 1.5 cutoff point had an area under the curve (AUC) of 0.955, with 75% sensitivity and 94.74% specificity, according to receiver operating characteristic curve analysis. However, the questionnaire’s cutoff point of ≥ 5 had an AUC of 0.720, 75% sensitivity, and 63% specificity, with improved overall instrument performance when combining both scores. Regarding blood biomarkers, serum NSE had greater sensitivity and specificity in discriminating neuropathic patients than HSP27 (92% and 74% versus 75% and 71%, respectively). Regression analysis revealed a substantial dependency for MNSI and serum NSE in predicting DPN in patients.ConclusionsDespite limited research in pediatrics, MNSI and serum NSE are promising predictive tools for DPN in children and adolescents with T1DM, even when they are asymptomatic. Poor glycemic control and lipid profile changes may play a critical role in the development of DPN in these patients, despite conflicting results in various studies.

Education, urbanicity of residence, and cardiometabolic biomarkers among middle-aged and older populations in the US, Mexico, China, and India

BackgroundThe relationship between education and cardiometabolic biomarkers is contextually dependent on both inter-country and intra-country factors. This study aimed to examine educational differences in cardiometabolic biomarkers among middle-aged and older adults in the US, Mexico, China, and India, and whether this relationship is modified by urbanicity of residence. MethodsData were from contemporary cross-sectional waves of the US Health and Retirement Study (HRS; 2016/17, n = 19,608), the Mexican Health and Aging Study (MHAS; 2015, n = 12,356), the China Health and Retirement Longitudinal Study (CHARLS; 2015/16, n = 13,268), and the Longitudinal Aging Study in India (LASI; 2017/19, n = 47,838). To account for substantial variations in educational distribution across the four countries, we measured education attainment in two ways: by categorizing education levels into binary classifications (‘lower education: lower secondary education or below' vs. 'higher education: upper secondary education or above') to assess absolute education attainment, and by using within-country percentile ranks to capture relative education attainment. We assessed educational differences in four cardiometabolic biomarkers: body mass index (BMI), systolic blood pressure (SBP), glycated haemoglobin (HbA1c), and total cholesterol. We tested whether urbanicity of residence modified the relationship between education and these cardiometabolic biomarkers. ResultsThe proportion of individuals with higher education was 82.6% in the US, 15.6% in Mexico, 10.6% in China, and 16.8% in India. In the US, higher education was associated with lower SBP (−2.74 mmHg, 95% CI: −3.62, −1.86) and HbA1c (−0.14%, 95% CI: −0.20, −0.08), but higher total cholesterol (3.33 mg/dL, 95% CI: 1.41, 5.25). In Mexico, higher education was associated with lower BMI only (−0.51 kg/m2, 95% CI: −0.76, −0.26). In China, higher education was not associated with any biomarker. In India, higher education was associated with higher BMI (1.61 kg/m2, 95% CI: 1.49, 1.73), SBP (1.67 mmHg, 95% CI: 1.16, 2.18), and HbA1c (0.35%, 95% CI: 0.19, 0.51). The association between education and cardiometabolic biomarkers was modified by urbanicity in China and India but not in the US or Mexico. In both China and India, relationships between education and cardiometabolic biomarkers were stronger among rural residents compared to those among urban residents. Results based on relative education attainment showed similar patterns in terms of the direction of the effect estimates, despite some discrepancies in statistical significance. InterpretationThere is a complex relationship between education and cardiometabolic biomarkers across countries and by urbanicity of residence. This complexity underscores the importance of accounting for contextual factors when devising strategies to enhance cardiometabolic health in various settings.

Preoperative Glycosylated Hemoglobin A1C Impacts Long-Term Outcomes Following Curative-Intent Resection of Nonfunctional Gastroenteropancreatic Neuroendocrine Tumors.

To investigate the impact of preoperative glycosylated hemoglobin A1C (HbA1c) among patients following curative-intent resection of nonfunctional gastroentropancreatic neuroendocrine tumors (GEP-NETs). Patients who underwent curative-intent resection for GEP-NETs from 2000 to 2020 were identified from the US Neuroendocrine Tumor Study Group (US-NETSG). Preoperative blood HbA1c levels were defined as high HbA1c (≥ 6.5%) versus low HbA1c group (< 6.5%). Impact of HbA1c level on postoperative short-term and long-term overall (OS) were investigated. A total of 130 patients with HbA1c < 6.5% and 60 patients with HbA1c ≥ 6.5% were included. Patients with HbA1c ≥ 6.5% had higher proportion of comorbidities, such as hypertension, obesity, anemia, and lower preoperative albumin levels versus patients with HbA1c < 6.5% (all p < 0.05). In addition, high level of preoperative HbA1c was associated with increased incidence of wound and infectious complications, as well as decreased long-term OS (median OS: high Hb1Ac 89.8 months vs. low Hb1Ac not reached, HR 3.487, p = 0.004) among patients with nonfunctional GEP-NETs, as well as among the subset of pancreatic NET patients (median OS: high Hb1Ac 74.3 months vs. low Hb1Ac not reached, p = 0.004), and patients with normal fasting blood glucose (< 140 mg/dL) (median OS: high Hb1Ac 75.4 months vs. low Hb1Ac not reached, p = 0.001). Hb1Ac might have value as a screening tool to identify high-risk patients following surgical resection of nonfunctional GEP-NETs for consideration of more strict postoperative surveillance and treatment of elevated Hb1Ac level.

12600 Predictors Of Diabetes Remission: The Impact Of Early Intervention Through A Digital Twin Platform

Abstract Disclosure: S.R. Joshi: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. M. Thajudeen: None. A. Balasubramanian: None. M. Panandikar: None. P. Shamanna: None. Introduction and Objective: Digital twin (DT) platform uses Artificial Intelligence (AI) and Internet of Things, to integrate multi-dimensional data for precision nutrition and health recommendations via the mobile app. We aimed to identify the pre-intervention anthropometric and biochemical parameters that predict diabetes remission (HbA1c &amp;lt; 6.5% without medications for over 3 months). Methods: 209 patients with T2D completed 540 days (18 months) of DT intervention. Results: 129 (61.7%) achieved remission of T2DM (R group). At baseline, patients in R group, compared with patients in the Non-remission Group (group NR) (n=80) had shorter duration of diabetes (yrs) (R: 2.9±2.6, 95% CI 2.5 to 3.4) vs. (NR: 4.7±2.2, 95% CI 4.2 to 5.2), p= &amp;lt;0.0001; lower baseline HbA1c % (R: 8.6±1.9, 95% CI 8.3 to 9) vs. (NR: 9.5±1.7, 95% CI 9.1 to 9.9), p=0.0008; lower estimated HbA1c (eA1C) (R: 7.6±2.2, 95% CI 7.2 to 8) vs. (NR: 8.9±2.3, 95% CI 8.4 to 9.4), p= &amp;lt;0.0001; lower glucose management indicator (GMI) % (R: 7.5±1.6, 95% CI 7.2 to 7.8) vs. (NR: 8.4±1.8, 95% CI 7.9 to 8.8), p=0.0006; ; lower Time Above Range level 1 (TAR1 %; target 180-250 mg/dl &amp;lt; 25% time) (R:21.3±17.6, 95% CI 18.2 to 24.4) vs. (NR: 31.2±17.2, 95% CI 27.3 to 35), p&amp;lt;0.0001; lower Time Above Range level 2 (TAR2 %; target &amp;gt;250 mg/dl &amp;lt; 5% time) (R: 15±24.5, 95% CI 10.8 to 19.3) vs. (NR: 24.2±26.3, 95% CI 18.2 to 29.9), p=0.01; higher Time In Range (TIR; target 70-180 mg/dl &amp;gt;70% time) (R: 59.5±31.5, 95% CI 54 to 65) vs. (NR: 43.3±30.9, 95% CI 36.4 to 50.2), p=0.0003; lower fasting plasma glucose (mg/dl) (R: 161±53.4, 95% CI 151.7 to 170.3) vs. (NR: 186.4±69.3, 95% CI 171 to 201.8), p=0.003; higher HOMA2B (%) (R: 56.6±31.7, 95% CI 51.1 to 62.1) Vs (NR: 43.6±27.5, 95% CI 37.4 to 49.6), p=0.002; and comparable fasting insulin (mIU/L) (R: 13.9±10.1, 95% CI 12.2 to 15.7) vs. (NR: 11.8±7.2, 95% CI 10.2 to 13.4), p=0.09 (ns), HOMA2IR (%) (R:1.9±0.93, 95% CI 1.8 to 2.1) vs (NR:1.8±0.84, 95% CI 1.6 to 2), p=0.33 (ns); weight (kg) (R:78.9±14.4, 95% CI 76.2 to 81.6) vs (NR:78.1±12.8, 95% CI 75.3 to 81), p=0.71 (ns). The mean baseline anti-diabetic drug count was lower in R (1.4) Vs NR (2.1). At 540 days the change was as follows: comparable Time Below Range1 - TBR1 %(&amp;lt; 70-54 mg/dl) &amp;lt; 4% (R: 3.5±14.9, 95% CI 0.92 to 6.1) Vs (NR: 1.9±8.3, 95% CI 0.07 to 3.8), p=0.38 (ns); lower HbA1c (R: 5.9±0.35, 95% CI 5.8 to 6) Vs (NR: 7.2±1.1, 95% CI 7 to 7.5), p&amp;lt;0.0001. Conclusion: Shorter diabetes duration, lower baseline HbA1c, eA1C, GMI, and TAR, higher TIR, lower fasting plasma glucose, and higher beta-cell function are key predictors of diabetes remission. Presentation: 6/3/2024

6519 BCG Clinical Trial Programs in Advanced Type 1 Diabetes - 2024 Update

Abstract Disclosure: W.M. Kühtreiber: None. B. Thach: None. H. Hayashi: None. L. Adams: None. N. Hullavarad: None. D.A. Mounier: None. K. Le: None. E. Bulczynski: None. J.L. Dorsey: None. N. Kartsounis: None. J. Braley: None. H. Zheng: None. D.L. Faustman: None. The bacillus Calmette-Guerin (BCG) vaccine, originally developed a century ago to prevent tuberculosis infection, has today advanced in multiple clinical trials for the treatment of the type 1 diabetes (T1D), other forms of autoimmunity and infectious disease. At our institution, over 500 individuals with type 1 diabetes have been enrolled in ongoing BCG clinical protocols to test BCG’s ability to lower HbA1c, reduce insulin requirements and stabilize day-to-day fluctuations in blood sugars; 300 have been treated with BCG. In a completed randomized, placebo-controlled Phase I trial in adults with established T1D, long-term follow up continues to show that HbA1c values are durably lowered for 8+ years after multi-dose BCG treatment. In two open-label clinical trials in adults with juvenile-onset diabetes, a 10-15% reduction of HbA1c was observed after multi-dose BCG treatment. A randomized, double-blinded Phase II trial in adults with longstanding T1D has followed all patients in the BCG-treated (n=100) and placebo groups (n=50) for five years and is pending read-out. The primary outcome of all the trials is HbA1c lowering. Two new, randomized, double-blinded pediatric trials are testing the potential benefits of BCG vaccination with active enrollment ongoing. One is testing BCG in children ages 12 to 18 with more than 2 years since T1D diagnosis. The other is enrolling children ages 8 to 18 with less than 1 year since T1D diagnosis. BCG vaccine therapy may provide a safe and affordable medical intervention in individuals with longstanding T1D and works decades after disease onset by changing glucose metabolism within lymphocytes, independently of the pancreas. Presentation: 6/3/2024

7490 Comparative Clinical Analysis of DPP-4 inhibitors and SGLT2 inhibitors; Switch Study in Real-World Setting

Abstract Disclosure: H. Choe: None. M. Kwak: None. J. Lee: None. Y. Choi: None. E. Hong: None. Objective: Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) represent two distinct pharmacological pathways in the management of type 2 diabetes, both aiming to improve glycemic control without risk of hypoglycemia. Metabolic implications and glycemic control associated with the interchange between SGLT2i and DPP-4i are scarce. This study aimed to evaluate the effect of switching between SGLT2i and DPP4i on various clinical parameters in Korean patients with type 2 diabetes. Methods: We conducted a retrospective cohort study at Hallym University Dongtan Sacred Heart Hospital, using clinical data warehouse. Baseline measurements and follow-up data at 3 months were collected for parameters including hemoglobin A1c (HbA1c), blood pressure, lipid profile, liver enzymes, renal function, and other metabolic markers. Results: Between 2015 and 2023, 104 participants switched from SGLT2 inhibitors to DPP4 inhibitors, while 321 switched in the opposite direction. Initially, those who switched from SGLT2 inhibitors to DPP4 inhibitors presented with lower baseline HbA1c levels (7.22 ± 0.73% versus 7.42 ± 0.76%, P = 0.017) and higher estimated glomerular filtration rates (eGFR) (95.2 ± 23.1 versus 85.9 ± 23.7 mL/min/1.73m², P = 0.001) compared to those who switched from DPP4 inhibitors to SGLT2 inhibitors. At three months of follow-up, the SGLT2 inhibitors to DPP4 inhibitors group exhibited a more significant reduction in HbA1c (adjusted β 0.22, 95% CI 0.03 to 0.40, P = 0.023), especially in patients with reduced eGFR (&amp;lt;60 mL/min/1.73 m²) (β 1.2, 95% CI 0.30 to 2.11, P = 0.013; P for interaction = 0.005). On the other hand, the DPP4 inhibitors to SGLT2 inhibitors group showed a greater decrease in fasting glucose levels (β -9.73, 95% CI -17.6 to -1.86, P = 0.016), along with more pronounced reductions in liver enzymes AST (β -4.15, 95% CI -6.49 to -1.81, P &amp;lt; 0.001) and ALT (β -6.42, 95% CI -9.58 to -3.27, P &amp;lt; 0.001), and a significant increase in hematocrit (β 3.31, 95% CI 2.36 to 4.26, P &amp;lt; 0.001) compared to the initial group. Conclusions: The study concludes that in Korean patients with type 2 diabetes, switching from SGLT2 inhibitors to DPP4 inhibitors is associated with a greater reduction in HbA1c, particularly in those with reduced renal function. Conversely, switching from DPP4 inhibitors to SGLT2 inhibitors results in more substantial improvements in fasting glucose and liver enzyme levels, suggesting differential benefits depending on the direction of the medication switch. Presentation: 6/3/2024

6527 Genetic variants may influence the glycemic response to sodium-glucose cotransporter-2 inhibitors in the Mass General Brigham Biobank

Abstract Disclosure: J.H. Li: None. A. Barry: None. A. Huerta-Chagoya: None. L. Szczerbinski: None. J.M. Mercader: None. J.C. Florez: Consulting Fee; Self; AstraZeneca. Grant Recipient; Self; Novo Nordisk. Speaker; Self; Novo Nordisk, Merck. A. Leong: None. Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are increasingly prescribed for the treatment of type 2 diabetes, but there is interindividual variability in glycemic response. We investigated whether two genetic variants, rs33954001, a missense variant (p.His615Gln) in SLC5A1 encoding SGLT1, and rs8050500 near SLC5A2 encoding SGLT2, previously associated with glycemic traits in genome-wide association studies, had any influence on short-term glycated hemoglobin (HbA1c) lowering in patients on SGLT2i treatment. Methods: We identified 1,961 ancestrally diverse, genotyped individuals with documented exposure to a SGLT2i in the Mass General Brigham Biobank, a hospital-based biobank linked with patient medical records. Of these, 736 individuals had a baseline HbA1c ≥ 6% within 6 months of the index appearance of an SGLT2i and a follow-up HbA1c measured 6-12 months after. Genotyping was performed on the Illumina Multi-Ethnic Genotyping Array and the Illumina Global Screening Array. Variants were imputed with the TOPMed reference panel. Using linear regression models, we evaluated the additive effect of the genetic variants on HbA1c reduction, defined as baseline HbA1c minus follow-up HbA1c, adjusted for age, sex, 10 genetic ancestry principal components to account for population stratification, the number of concomitant glucose-lowering drug classes, and three covariates accounting for potential genotyping batch effects. To determine whether genetic effects varied by pretreatment glycemic control, we tested for a genotype × baseline HbA1c interaction and performed stratified analysis by baseline HbA1c (≥ 8% vs. &amp;lt; 8%). Results: The mean age of participants was 63.7 years and 41% were female. The baseline HbA1c was 8.0 ± 1.9%. The mean HbA1c reduction was 0.6% over a mean follow-up time of 8.7 ± 1.6 months. None of the variants were associated with HbA1c reduction (p &amp;gt; 0.05) in the whole dataset. However, in stratified analyses, among those with baseline HbA1c ≥ 8% (n = 382), we observed that carriers of the G allele at rs33954001 had a 0.5% greater HbA1c reduction (p = 0.048) compared to those with CC genotype. Further adjustment for baseline renal function did not modify results. In the Genotype-Tissue Expression (GTEx) portal, the G allele was associated with higher SLC5A1 expression in nerve (p = 1 × 10-8), esophageal mucosa (p = 4 × 10-5) and stomach (p = 9 × 10-5), but not kidney. In the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER), the G allele was associated with SLC5A1 expression in pancreatic islets (p = 2 × 10-6). Conclusion: Genetic variation in SLC5A1 may partly explain heterogeneity in SGLT2i treatment effects among people with sub-optimally controlled diabetes, possibly due to differences in SLC5A1 tissue-specific expression. These findings require validation in large hospital-based biobanks or dedicated clinical trials. Presentation: 6/2/2024

8156 Exploring Gender-Specific Characteristics Of Diabetes Among Young Adults In Korea: The Korea National Health And Nutrition Examination Survey 2011-2012 And 2019-2020

Abstract Disclosure: C. Chung: None. Background: The escalating global incidence of diabetes among young adults could be linked to dynamic socio-environmental changes including pandemic and climate shifts. In this investigation, we aimed to discern the distinct features of diabetes among young adults in Korea. Methods: This cross-sectional study included 63,489,047 Korean young adults (32,173,248 male, 31,315,799 female) aged 20-39 years who participated in the Korean National Health and Nutrition Examination Survey 2011-2012 and 2020-2021. Diabetes cases were identified through hospital diagnoses or the prescription of insulin or non-insulinemic anti-diabetic medications. The significant insulin resistance was defined as HOMA-IR above 2.9. Complex sampling design and cross-tabulation analyses were used to examine both socioeconomic and laboratory factors. Results: The prevalence of diabetes was higher in men in both 2011-2012 and 2020-2021 (Men vs. Women, 2011-2012: 2.2 ± 0.5 vs. 1.2 ± 0.3 %, p&amp;lt;0.001; 2020-2021: 3.0 ± 0.5 vs. 1.6 ± 0.3 %, p&amp;lt;0.001). The use of insulin and oral hypoglycemic agent (OHA) was comparable between men and women in 2011-2012 (Insulin: 18.1 ± 8.2 vs. 5.2 ± 5.1 %, p=0.305; OHA, 18.2 ± 6.3 vs. 19.5 ± 6.5 %, p=0.239), but more women used insulin and more men used OHA in 2020-2021 (Insulin: 5.3 ± 3.7 vs. 28.7 ± 9.4 %, p=0.016; OHA: 31.4 ± 7.7 vs. 19.6 ± 7.3 %, p=0.009). Execution of fundus exam (25.7 ± 10.6 vs. 68.5 ± 14.1 %, p=0.021) and diagnosis of diabetic retinopathy (0 vs. 8.9 ± 3.3 %, p=0.001) was higher in women in 2020-2021. HbA1c was higher in men in 2020-2021 (8.1 ± 0.4 vs. 7.3 ± 0.3 %, p &amp;lt;0.001), but was similar between men and women in 2011-2012 (8.4 ± 0.6 vs. 8.1 ± 0.6 %, p=0.697). Obesity, one of the most common comorbidities of diabetes, was higher in women in 2011-2012 (24.8 ± 4.8 vs. 79.4 ± 9.3 %, p&amp;lt;0.001), but was higher in men in 2020-2021 (94.4 ± 2.9 vs. 67.8 ± 11.0 %, p&amp;lt;0.001). The factors associated with increase in HOMA-IR in 2020-2021 was different between men and women. Unexpectedly, men with low mental stress showed positive correlation with HOMA-IR (B = 3.9, 95% CI 0.1-7.7, p=0.047). For women, mental stress did not affect HOMA-IR, but those with regular anaerobic exercise (B = -10.5, 95% CI -18.3 - -2.6, p=0.011) and stable employment status (B = -11.9, 95% CI -19.4 - -4.8, p=0.002) presented negative correlation with HOMA-IR. Conclusion: In comparison to before the COVID-19 pandemic, men diabetic patients showed more obese tendency after COVID-19, and there was also a statistically significant difference in HbA1c disparity with women. The higher prevalence of diabetic retinopathy despite of lower HbA1c in women during pandemic era needs to be further investigated in well-designed cohort study. Presentation: 6/3/2024

Evaluating the relationship between glycemic control and bone fragility within the UK Biobank: observational and one-sample Mendelian randomization analyses.

We aimed to: (1) examine the relationship between glycemic control, BMD estimated from heel ultrasound (eBMD) and fracture risk in individuals with type 1 (T1D) and type 2 diabetes (T2D) and (2) perform a one-sample Mendelian randomization (MR) study to explore potential causal associations between glycemic control, eBMD, and fractures. This study comprised 452 131 individuals from the UK Biobank with glycated hemoglobin A1C (HbA1c) and eBMD levels. At baseline, 4078 participants were diagnosed with T1D and 23 682 with T2D. HbA1c was used to classify patients into "adequately-" (ACD; n = 17 078; HbA1c < 7.0%/53mmol/mol) and "inadequately-" (ICD; n = 10 682; HbA1c ≥ 7.0%/53mmol/mol) controlled diabetes. In individuals with T1D, a 1% unit (11mmol/mol) increase in HbA1c levels was associated with a 12% increase in fracture risk (HR: 1.12, 95% CI [1.05-1.19]). Fracture risk was highest in individuals with T1D and ICD (HR 2.84, 95%CI [2.53, 3.19]), followed by those with ACD (HR 2.26, 95%CI [1.91, 2.69]), as compared to subjects without diabetes. Evidence for a non-linear association between HbA1c and fracture risk was observed (F-test ANOVA p-value = 0.002) in individuals with T2D, with risk being increased at both low and high levels of HbA1c. Fracture risk between the T2D ACD and ICD groups was not significantly different (HR: 0.97, 95%CI [0.91-1.16]), despite increased BMD. In MR analyses genetically predicted higher HbA1c levels were not significantly associated with fracture risk (causal risk ratio: 1.04, 95%CI [0.95-1.14]). We did observe evidence of a non-linear causal association with eBMD (quadratic test p-value = 0.0002), indicating U-shaped relationship between HbA1c and eBMD. We obtained evidence that lower HbA1c levels will reduce fracture risk in patients with T1D. In individuals with T2D, lowering HbA1c levels can mitigate the risk of fractures up to a threshold, beyond which the risk may begin to rise again.

Hemoglobin A1c Genetics and Disparities in Risk of Diabetic Retinopathy in Individuals of Genetically Inferred African American/African British and European Ancestries.

Individuals with diabetes who carry genetic variants that lower hemoglobin A1c (HbA1c) independently of glycemia may have higher real, but undetected, hyperglycemia compared with those without these variants despite achieving similar HbA1c targets, potentially placing them at greater risk for diabetes-related complications. We sought to determine whether these genetic variants, aggregated in a polygenic score, and the large-effect African ancestry-specific missense variant in G6PD (rs1050828) that lower HbA1c were associated with higher retinopathy risk. Using data from 29,828 type 2 diabetes cases of genetically inferred African American/African British and European ancestries, we calculated ancestry-specific nonglycemic HbA1c polygenic scores (ngA1cPS) composed of 122 variants associated with HbA1c at genome-wide significance, but not with glucose. We tested the association of the ngA1cPS and the G6PD variant with retinopathy, adjusting for measured HbA1c and retinopathy risk factors. Participants in the bottom quintile of the ngA1cPS showed between 20% and 50% higher retinopathy prevalence, compared with those above this quintile, despite similar levels of measured HbA1c. The adjusted meta-analytic odds ratio for the bottom quintile was 1.31 (95% CI 1.0, 1.73; P = 0.05) in African ancestry and 1.31 (95% CI 1.15, 1.50; P = 6.5 × 10-5) in European ancestry. Among individuals of African ancestry with HbA1c below 7%, retinopathy prevalence was higher in individuals below, compared with above, the 50th percentile of the ngA1cPS regardless of sex or G6PD carrier status. Genetic effects need to be considered to personalize HbA1c targets and improve outcomes of people with diabetes from diverse ancestries.

TNF-α inhibitors for type 1 diabetes: exploring the path to a pivotal clinical trial.

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.

PENGARUH KONSELING APOTEKER TERHADAP KEPATUHAN TERAPI PASIEN DIABETES MELITUS DI BEBERAPA PUSKESMAS DAN RUMAH SAKIT

Diabetes mellitus is a global health issue that requires a comprehensive management approach. Pharmacist interventions have proven effective in enhancing patient adherence to medication and improving clinical outcomes. This study aims to systematically review pharmacist interventions for diabetes mellitus patients and their impact on medication adherence and glycemic control. The research method used was a narrative literature review, analyzing 188 articles from PubMed and 200 articles from Google Scholar, with 20 studies meeting the inclusion criteria, including 12 studies conducted in community health centers (puskesmas) and 8 studies in hospitals. The findings indicate that pharmacist counseling interventions significantly improve medication adherence and lower HbA1c levels. In community health centers, adherence increased from 9.2% to 61%, and HbA1c decreased from 8.5% to 7.2%. In hospitals, the average HbA1c reduction was between 1.5% and 2%. The multifaceted counseling approach was more effective compared to telephone counseling, which showed an HbA1c reduction of 0.3%. These findings highlight the critical role of pharmacists in managing type 2 diabetes mellitus.

Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia

BackgroundHyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.MethodsThe acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.ResultsLevels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.ConclusionsBiomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.

Minimally Invasive Distal Metatarsal Diaphyseal Osteotomy (MIS-DMDO) for the Prevention and Treatment of Chronic Plantar Diabetic Foot Ulcers.

Diabetic foot is one of the major complications of diabetes, affecting 15% of patients with diabetes. This study aims to evaluate and compare the clinical and radiographic outcomes of patients with diabetes affected by forefoot plantar preulcerative or ulcerative lesions who have undergone minimally invasive distal metatarsal diaphyseal osteotomy (MIS-DMDO) to assess its efficacy in the prevention and treatment of chronic plantar diabetic foot ulcers (CPDFUs). The study included 60 patients, 38 with preulcers and 22 with ulcers, with at least 2 years of clinical and radiologic follow-up. Clinical outcomes were assessed using the European Foot and Ankle Society (EFAS) score, the Foot Function Index (FFI), and the Manchester-Oxford Foot Questionnaire (MOXFQ). The radiographic evaluation was performed according to the Maestro criteria. Both groups improved in clinical and radiologic outcomes when comparing baseline measurements to those at the final follow-up. There were no statistical differences between preulcer and ulcer groups in terms of both clinical and radiologic outcomes, with the only exception being FFI, which was lower in the preulcerative group. In multivariate analysis, gender and glycated hemoglobin (HbA1c) were predictors of better outcomes. Specifically, FFI and MOXFQ (P < .05) exhibited larger improvements in females, while Maestro 1 and 2 were better in patients with lower HbA1c (P < .05). All patients were considered healed at the final follow-up. Carefully performed minimally invasive distal metatarsal diaphyseal osteotomy can be an effective approach to the care of impending or chronically present plantar diabetic foot ulcers.