American Diabetes Association Research Articles

Expert opinion regarding early screening, patient awareness, and telemedicine practices in Indian settings

Objective: To collect clinicians’ perspectives regarding the significance of early screening, patient awareness, and telemedicine practice in routine Indian settings for diabetes management. Methodology: The study employed a 25-item questionnaire to gather insights from specialists across different Indian settings regarding their perspectives on early screening, patient awareness, and telemedicine practices among diabetologists. Results: According to the cross-sectional survey, 59% of respondents believed that regular awareness programs were helpful in the early screening of diabetes among high-risk individuals. Meanwhile, 64% of clinicians reported that clinical-level screening was a more effective tool for early screening. Around 74% of clinicians reported that microvascular complications namely diabetic retinopathy, diabetic neuropathy, and diabetic kidney diseases should be targeted during early screening of diabetes. The American Diabetes Association (ADA) risk score was the most commonly used risk score for early diabetes screening, according to 54% of clinicians. Moreover, 67% of clinicians reported that 11 to 25% of diabetic individuals had complications of lipitension, and 64% reported that 11 to 20% of T2DM individuals had depression. Regarding telemedicine, 65% of clinicians preferred to use it occasionally. However, at an individual level, factors like cost, literacy, less familiarity with using the tool, and emotional reasons hindered the effective adoption of telemedicine, as reported by 56% of clinicians. Conclusion: The survey highlighted the effectiveness of awareness programs and clinical-level screening for early diabetes management, emphasizing the importance of targeting microvascular complications. Increased prevalence of complications like lipitension and depression was noted in diabetic individuals. Telemedicine, though recognized as valuable, faces challenges due to individual-level factors.

Type 2 diabetes mellitus: Prevalence and risk factors associated, among patients at Franceville Amissa Bongo regional Hospital, Gabon

Introduction: To assess the type 2 diabetes mellitus prevalence and risk factors associated, among patients, at Franceville Amissa Bongo regional Hospital Gabon, A prospective and cross-sectional study was carried out between June and September 2023. Materials and Methods: Blood glucose was measured using blood drawn from each participant, according to American Diabetes Association standards. As elsewhere, correlations between type 2 diabetes mellitus prevalence and the variables obtained, were carried out using R software version 3.6.1. Odds ratios were calculated within a 95% interval, and results were considered significant when the p-value ≤ 0, 05. Results: Blood samples from 328 people, with a mean age of 48.24 ± 13.8 years, were collected for this study. The type 2 diabetes mellitus prevalence was 13.72% (95% CI: [0.10- 0.18]), (n=45). After univariate analysis, adjustment of variables by binary multivariate logistic regression, indicated female gender (Ajusted OR = 0.53; 95% CI [1.52; 39.41] p = 0.014*), cohabiting (Ajusted OR = 92.73 ; 95% CI [2.9; 29.05] p = 0.010*), inactive (Ajusted OR = 9.17; 95% CI: [1.11; 75.05] p = 0.040*), overweight/obese (Ajusted OR = 0. 017; 95% CI: [0.002; 0.18] p = 0.010*), a family history of type 2 diabetes mellitus (Ajusted OR = 50.13; 95% CI [8.87; 283.50] p = 0.000*) and high triglyceride levels (Ajusted OR = 0.03; 95% CI [0.003; 0.36] p = 0.005*), as type 2 diabetes mellitus potential risk factors, in the present study. Conclusion: The type 2 diabetes mellitus prevalence in the study population was high. Prevention and control of this disease through early detection are essential.

#1888 Association between intrapatient variability of serum tacrolimus levels with the development of diabetes in post-kidney transplantation patients

Abstract Background and Aims Kidney transplantation is the most cost-effective renal replacement therapy compared to dialysis. Diabetes is main cause of increased cardiovascular risk and death. Post-transplant Diabetes Mellitus (PTDM) it refers to presence of diabetes in an environment after kidney transplantation; According to the ADA (American Diabetes Association) criteria, the diagnosis must be made with a tolerance test with 75 grams of oral glucose (Oral glucose tolerance test-OGTT) or the determination of glycosylated hemoglobin 1Ac (Hb1Ac) in a post-transplant period of stability of the immunosuppression dose and without infections. There are various risk factors for the development of PTDM: hypomagnesemia, glucocorticoids, calcineurin inhibitors (tacrolimus and cyclosporine); hepatitis C virus and cytomegalovirus infections. In a Mexican kidney transplant recipients in Guadalajara, Andrade SG demonstrated that the incidence of PTDM was 10.1% at 1 year post-transplant. In the Spanish population, Porrini E demonstrated that tacrolimus represents a risk factor for the development of PTDM, increasing the incidence of prediabetes by 33% at 12 months post-transplant. Several mechanisms have been implicated in the association of calcineurin inhibitor and PTDM: decreased insulin secretion, glucose intolerance, reduced pancreatic beta cell mass, increased islet apoptosis and decreased insulin gene expression. Studies mention that tacrolimus (FK) is more diabetogenic than cyclosporine (CsA) especially at levels above 20 ng/mL. The DIRECT study (Diabetes Incidence after Renal Transplantation) showed the incidence in 73 kidney transplant patients with CsA (26%) and 96 FK patients (33.6%, p = 0.046). By the other side, Malik RF mentions that FK levels aren´t a risk factor for the development of PTDM. To demonstrate that the high intrapatient variability of tacrolimus/cyclosporine serum levels correlates with the development of diabetes (PTDM) in kidney transplant recipients at the central military hospital in Mexico City. Method Observational, analytical, longitudinal and retrospective study. All kidney transplant recipients from living donors and cadaveric donors from January 2002 to December 2020 were included. FK and CsA were used as maintenance immunosuppression. Serum levels of FK/CsA, Hb1Ac and glucose were measured at months 0, 3, 6, 9 and 12 and intra-patient variability (IPV) of FK/CsA levels was calculated for each patient. The patients were separated into 2 groups, IPV low and IPV high according to the mean the coefficient of variability (CV). The IPV of the calcineurin inhibitor was estimated by calculating the CV in each patient according to the following equation: CV(%)= (SD/mean trough concentration of FK/ CsA)×100. The diagnosis of PTDM followed the criteria of the American Diabetes Association. The Mann Whitney U test was used. Results 638 kidney transplant recipients were included. The mean age of the recipients was 36.78 (±12.81) years. At the time of kidney transplant, the BMI was 22.67 (±3.90) and 25.76 (±3.99) kg/m² BS at 1 year post-transplant for whole cohort. At 1 year post-transplant, 72.3% patients were on FK and 27.7% on CsA. Hb1Ac for whole cohort was 4.81 (±0.71)% and 4.84 (±0.77)% at month 0 and 12 post-kidney transplant, respectively. FK and CsA levels were 12.41 (±5.31) and 234.34 (±87.80) ng/mL and 9.13 (±5.3) and 194.38 (±92.44) ng/mL in the PTDM and non-PTDM groups, respectively (p = 0.029). 17.96% of patients developed PTDM. Mean CV of the entire cohort was 33.84 (±20.41)%. When performing the analysis of the IPV coefficient by subgroups of maintenance immunosuppression used at 1 year post-transplant: the IPV of FK was 43.39 (±18.49)% and 29.99 (±17.56)% in the PTDM and non-PTDM groups respectively, p = 0.000, which shows that patients with a high IPV coefficient of tacrolimus developed more PTDM than those with low variability, student's t-test to compare IPV was 0.03. The IPV of CsA was 38.61 (±18.76)% and 37.51 (±25.67)% in the PTDM and non-PTDM groups respectively, p = 0.819. Conclusion High intrapatient variability of tacrolimus was correlated with the development of PTDM in Mexican kidney transplant recipients.

Metabolic syndrome and pharmacotherapy outcomes in patients with type 2 diabetes mellitus

BackgroundMetabolic syndrome is a group of metabolic abnormalities that increase predisposition to several diseases including ischemic heart disease and diabetes mellitus. The study aimed to investigate metabolic syndrome among patients with type-2 diabetes mellitus (DM), and its impact on pharmacotherapy outcomes.MethodsAn observational cross-sectional study was performed on 910 patients with type-2 DM between June and December 2023. Fasting blood sugar, triglycerides, high-density lipoproteins (HDL), blood pressure, and abdominal obesity were measured. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Pharmacotherapy outcomes were assessed according to American Association of Clinical Endocrinologists and American Diabetes Association guidelines using the ability to achieve adequate glycemic control and normal levels of blood pressure and fasting plasma lipoproteins.ResultsIn total, 87.5% of type-2 DM patients had metabolic syndrome; the prevalence increased with age and was higher among females. Metabolic syndrome showed the following distribution of risk factors: insulin resistance (100%), low HDL (95.3%), elevated blood pressure (83%), triglycerides dyslipidemia (80.1%), and abdominal obesity (62.5%). Majority of the patients had either 5 or 4 risk factors of metabolic syndrome. The most common comorbidities were dyslipidemia (97.7%) and hypertension (83%). Treatment outcomes were insufficient where adequate glycemic control was only achieved in 12% of type-2 DM patients, and proper management of comorbid dyslipidemia and hypertension was achieved in 29% and 40.9% of patients, respectively. Adequate blood pressure control was less achieved in patients with metabolic syndrome (34.4%) than those without metabolic syndrome (77.2%). Similarly, dyslipidemia was less controlled in patients with metabolic syndrome (26.9%) than in those without metabolic syndrome (47.3%).ConclusionPharmacotherapy outcomes were inadequate for most patients with type-2 diabetes mellitus. Adopting early preventive and therapeutic interventions for metabolic syndrome is advised to improve treatment outcomes of the comorbid dyslipidemia and hypertension.

Education of Hospitalized Diabetic Patients: Analysis of Training Needs among Nurses in a Lebanese Hospital – A Secondary Publication

The design of diabetes inpatient educational preparation should be based on the needs of the nurses involved in terms of skills in this area. The objective of this qualitative study is to identify the preparatory needs of nurses working in the medical and surgical units of a Lebanese hospital in terms of Survival Skills Education for Hospitalized Diabetic Patients (SSEHDP). Method: The focus group method is used for data collection using a semi-structured interview guide. The needs expressed by the thirty-two participating nurses were classified into categories of the competency framework for providing self-management education to diabetic patients proposed by the American Diabetes Association. Results: By focusing on the themes of an SSEHDP, a list of preparatory needs was drawn up. The needs identified and analyzed are then translated into general and specific learning objectives for educational preparation. Conclusion: The needs analysis is only the first step in a work that will ideally continue into the implementation and eventual evaluation of an educational program developed to help nurses acquire skills in the education of diabetic patients.

Evaluating adherence to American Diabetes Association standards of care in diabetes and impacts of social determinants of health on patients at two nurse practitioner-owned clinics.

The COVID-19 pandemic created barriers in the management of type 2 diabetes mellitus (T2DM) and worsened social determinants of health (SDOH). A New Hampshire primary care office worked to adhere to T2DM standards of care and began screening for SDOH. This project assessed adherence to quality metrics, hemoglobin A1C, and SDOH screening as telehealth utilization decreased. A1C values have increased at the practice, especially since COVID-19. The practice also began screening for SDOH at every visit, but there was need to assess how needs were being documented and if/how they were addressed. A retrospective chart review of patients with T2DM was performed. Demographic data and T2DM metrics were collected and compared with previous years and compared new versus established patients. Charts were reviewed to evaluate documentation of SDOH and appropriate referral. The practice transitioned from an increased utliization of telehealth back to prioritizing in-office visits. The practice also began routinely screening for SDOH in 2020; however, this process had not been standardized or evaluated. Adherence to nearly all quality metrics improved. Glycemic control improved after a year of nurse practitioner (NP) care, especially in new patients. All patients were screened for SDOH, but documentation varied, and affected patients had higher A1Cs, despite receiving comparable care. Nurse practitioners at this practice are adhering to American Diabetes Association guidelines, and A1C values improve under their care. Social determinants of health continue to act as unique barriers that keep patients from improving glycemic control, highlighting the need for individualized treatment of SDOH in T2DM care.

Erratum: 16. Diabetes Care in the Hospital: Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals. Clin Diabetes 2024;42:222 (doi: 10.2337/cd24-a016)

A table on the perioperative care of people with diabetes in the abridged version of section 16 of the American Diabetes Association’s Standards of Care in Diabetes—2024 contained typographical errors. The corrected version is as follows. The online version of this article (https://doi.org/10.2337/cd24-a016) has been updated to reflect this change. Perioperative Care A1C and glucose goals Elective surgery A1C goal: <8% (63.9 mmol/L) Blood glucose goal within 4 hours of surgery: 100–180 mg/dL (5.6–10.0 mmol/L) Medication adjustments Hold metformin on the day of surgery. Discontinue sodium–glucose cotransporter 2 inhibitors 3–4 days before surgery. Hold other oral glucose-lowering agents the morning of the surgery or procedure. There are few data on the safe use and/or influence of glucagon-like peptide 1 receptor agonists on glycemia and delayed gastric emptying in the perioperative period. Individualize plan based on clinical scenario and procedure/surgery. Insulin therapy adjustments Give half of NPH dose or 75–80% of long-acting analog insulin or adjust insulin pump basal rates based on diabetes type and clinical judgment.

Mean Platelet Volume as a Predictive Marker for GDM

Background: Gestational Diabetes Mellitus (GDM) is defined as first onset of any glucose intolerance diagnosed in pregnancy and certain proportion has risk of developing type 2 diabetes later in life, but risk of type 1 is also increased. Screening at the earliest and enhanced diagnostic tools can help reduce burden of GDM and further progression as it is majorly a lifestyle disease. One of the easiest and cost-effective inflammatory markers are thrombocyte indices. Objective: To determine the potential value of MPV, an inexpensive and easy tool obtained from routine complete blood picture used to study morphology of platelet and whether it can be an indicator in prediction of GDM. Methods: Hospital based comparative study was done on 100 antenatal women attending OPD during first trimester. Case group includes women with recently diagnosed GDM as per guidelines of American diabetes Association by one-step 2-hour 75g OGTT and the cut off values were considered as per IADPSG. MPV is assessed amongst cases and controls and its association was studied in both groups. Results: The present study observed that MPV values of the GDM patients were significantly higher than those compared to normal pregnancies. The current investigation reveals that MPV values in GDM patients significantly exceed those observed in normal pregnancies. Specifically, the median MPV in the GDM group is 8.6 (IQR: 6.9-11.2), while in the non-GDM group, it is 7.4 (IQR: 4.8-10.4). The Mann-Whitney U test yielded a statistic of 905, with a corresponding p-value of 0.0175, which falls below the significance threshold of 0.05. Hence, there exists a statistically significant disparity in MPV between the groups. Conclusion: GDM is found to have underlying chronic inflammatory background and varied insulin resistance which states that these parameters may exist even before clinically diagnosable glucose intolerance occurs. This may direct that GTT might not detect GDM if done early in pregnancy, but inflammatory markers might diagnose as they have already been existing. One such economical marker is the MPV as a part of routine CBC. Keywords: Mean Platelet Volume; Gestational Diabetes Mellitus; IADPSG; Exclusive Real World Evidence

Interplay Between the American Diabetes Association’s ABC Targets for Diabetes, Insulin Resistance Indices, and Dyslipidemia in Indian Type 2 Diabetes Patients

Interplay Between the American Diabetes Association’s ABC Targets for Diabetes, Insulin Resistance Indices, and Dyslipidemia in Indian Type 2 Diabetes Patients

Machine Learning Approach to Metabolomic Data Predicts Type 2 Diabetes Mellitus Incidence.

Metabolomics, with its wealth of data, offers a valuable avenue for enhancing predictions and decision-making in diabetes. This observational study aimed to leverage machine learning (ML) algorithms to predict the 4-year risk of developing type 2 diabetes mellitus (T2DM) using targeted quantitative metabolomics data. A cohort of 279 cardiovascular risk patients who underwent coronary angiography and who were initially free of T2DM according to American Diabetes Association (ADA) criteria was analyzed at baseline, including anthropometric data and targeted metabolomics, using liquid chromatography (LC)-mass spectroscopy (MS) and flow injection analysis (FIA)-MS, respectively. All patients were followed for four years. During this time, 11.5% of the patients developed T2DM. After data preprocessing, 362 variables were used for ML, employing the Caret package in R. The dataset was divided into training and test sets (75:25 ratio) and we used an oversampling approach to address the classifier imbalance of T2DM incidence. After an additional recursive feature elimination step, identifying a set of 77 variables that were the most valuable for model generation, a Support Vector Machine (SVM) model with a linear kernel demonstrated the most promising predictive capabilities, exhibiting an F1 score of 50%, a specificity of 93%, and balanced and unbalanced accuracies of 72% and 88%, respectively. The top-ranked features were bile acids, ceramides, amino acids, and hexoses, whereas anthropometric features such as age, sex, waist circumference, or body mass index had no contribution. In conclusion, ML analysis of metabolomics data is a promising tool for identifying individuals at risk of developing T2DM and opens avenues for personalized and early intervention strategies.

Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center

BackgroundDiabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice.MethodsRetrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010–2019 was conducted to identify T2D patients with SBHF. We defined “pure” DbCM when SBHF is associated solely with T2D and “mixed” SBHF when other medical conditions can contribute to SBHF. “Pure” DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF.ResultsOf 778,314 UCSD patients in 2010–2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with “mixed” SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of “pure” DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study.ConclusionsOur findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

Polygenic Risk Score Modifies the Association of HbA1c With Hearing Loss in Middle-Aged and Older Chinese: The Dongfeng-Tongji Cohort.

Evidence regarding the modifying effect of the polygenic risk score (PRS) on the associations between glycemic traits and hearing loss (HL) was lacking. We aimed to examine whether these associations can be influenced by genetic susceptibility. This cross-sectional study included 13,275 participants aged 64.9 years from the Dongfeng-Tongji cohort. HL was defined according to a pure tone average >25 dB in the better ear and further classified by severity. Prediabetes and type 2 diabetes (T2D) were defined based on the 2013 criteria from the American Diabetes Association. A PRS was derived from 37 single-nucleotide polymorphisms associated with HL. Multivariable logistic regression models were fitted to estimate the associations of PRS and glycemic traits with HL and its severity. Elevated fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and T2D were positively associated with higher HL risks and its severity, with odds ratios (ORs) ranging from 1.04 (95% CI 1.00, 1.08) to 1.25 (95% CI 1.06, 1.46). We also found significant interaction between HbA1c and PRS on risks of overall HL and its severity (P for multiplicative interaction <0.05), and the effects of HbA1c on HL risks were significant only in high PRS. Additionally, compared with normoglycemiain the low PRS, T2D was respectively associated with an OR of up to 2.00 and 2.40 for overall HL and moderate to severe HL in the high PRS (P for additive interaction <0.05). PRS modifies the association of HbA1c with HL prevalence among middle-aged and older Chinese.

Differential association of dietary scores with the risk of type 2 diabetes by metabotype.

We aimed to examine the association between dietary patterns and type 2 diabetes mellitus (T2DM) while considering the potential effect modification by metabolic phenotypes (metabotypes). Additionally, we aimed to explore the association between dietary scores and prediabetes. A total of 1460 participants (11.8% with T2DM) from the cross-sectional population-based KORA FF4 study were included. Participants, classified into three metabotype subgroups, had both their FSAm-NPS dietary index (underpinning the Nutri-Score) and ultra-processed foods (UPF) intake (using NOVA classification) calculated. Glucose tolerance status was assessed via oral glucose tolerance tests (OGTT) in non-diabetic participants and was classified according to the American Diabetes Association criteria. Logistic regression models were used for both the overall and metabotype-stratified analyses of dietary scores' association with T2DM, and multinomial probit models for their association with prediabetes. Participants who had a diet with a higher FSAm-NPS dietary index (i.e., a lower diet quality) or a greater percentage of UPF consumption showed a positive association with T2DM. Stratified analyses demonstrated a strengthened association between UPF consumption and T2DM specifically in the metabolically most unfavorable metabotype (Odds Ratio, OR 1.92; 95% Confidence Interval, CI 1.35, 2.73). A diet with a higher FSAm-NPS dietary index was also positively associated with prediabetes (OR 1.19; 95% CI 1.04, 1.35). Our study suggests different associations between poorer diet quality and T2DM across individuals exhibiting diverse metabotypes, pointing to the option for stratified dietary interventions in diabetes prevention.

Renal tubular (pro)renin receptor deletion does not protect against kidney injury in db/db mice

Background: The (pro)renin receptor (PRR) is a multifunctional protein implicated in blood pressure regulation and kidney fibrosis. Previous studies report enhanced PRR expression in non-diabetic and diabetic kidney disease. In this study, we investigated whether deletion of renal tubular PRR attenuates kidney injury in type 2 diabetes. Methods: Floxed PRR mice were bred with mice expressing Pax8 rtTA and LC1 transgenes and db/db mice (B6.BKS) to obtain renal tubular PRR knockout (KO)-db/db mice. Age matched non-diabetic floxed controls, db/db mice and PRRKO-db/db mice were studied at 16, 20, 26 and 30 weeks of age. To induce PRR deletion, PRRKO-db/db mice were treated with 2 mg/ml doxycycline for 12 days at 8-10 weeks of age. Only male mice were included in this study. Results: All mice survived until the end of the study (N=5-7 mice/group). Compared to controls, db/db mice and PRRKO-db/db mice had higher body weights despite similar food intake throughout the study (p&lt;0.001 by one-way ANOVA). PRRKO-db/db mice had higher urine volume and water intake compared to controls and db/db mice (p &lt;0.01 by ANOVA). Db/db mice had elevated non-fasting blood glucose levels (average: 472 mg/dl at 16 weeks, 292 mg/dl at 30 weeks) while PRR KO-db/db mice had modestly elevated blood glucose levels (average 255 mg/dl at 20 and 30 weeks) relative to controls (average: 150 mg/dl). Urinary albumin excretion was markedly elevated in PRRKO-db/db mice relative to db/db mice and controls throughout the study (950 ug/day vs db/db:145 ug/day, controls: 50 ug/day, p&lt;0.001). At 30 weeks, kidney histology by PAS stain showed minimal tubular injury, glomerulosclerosis or interstitial inflammation among all 3 groups. Interestingly, podocin staining by immunofluorescence was reduced in db/db mice but not PRR-KO db/db mice. Compared to control mice, db/db mice had similar KIM-1, NGAL and collagen-1 mRNA expression in kidney cortex and inner medulla. PRR KO db/db mice had increased cortical KIM-1, NGAL and collagen-I expression compared to control and db/db mice (p&lt;0.01 by ANOVA). Plasma sPRR levels were almost two-fold higher in diabetic mice relative to controls with no difference between db/db mice and PRR KO-db/db mice. Urinary sPRR levels were undetectable in controls and mildly elevated in db/db mice (7.6 ± 0.7 pg/day) and PRR KO-db/db mice (47.6 ± 22.3 pg/ml). No differences in plasma prorenin/renin concentration was noted among the 3 groups while urinary prorenin/renin excretion was higher in PRRKO-db/db mice. Conclusion: Renal tubular deletion of PRR does not protect against kidney injury in type 2 diabetes. It is possible that loss of PRR impairs baseline tubular function which is exacerbated by type 2 diabetes. American Diabetes Association. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Metabolic syndrome reduces cerebral blood flow more in women than men

One in three adults in the United States suffers from metabolic syndrome (MetSyn), a state of insulin resistance associated with reduced cerebral blood flow (CBF) and increased risk of stroke and neurologic diseases. Notably, females are at greater risk for cardiovascular and metabolic complications derived from insulin resistance. Still, it remains unclear whether the reduction in CBF seen in MetSyn is sex-specific or uniform between various brain regions. Additionally, fasting triglyceride (TG) levels are stronger predictors of cognitive disease in females than in males. However, little data exist examining the relationship between TG and CBF in females with MetSyn. Therefore, we aimed to examine the interaction between sex and MetSyn on global and regional CBF in young adults and to explore the relationship between fasting TG levels and CBF. We predict that males and females with MetSyn will have lower global and regional CBF compared to healthy controls of the same sex, but to a greater extent in females with MetSyn. Additionally, we predict fasting TG levels will have stronger relationships with CBF in females than in males with MetSyn. Twenty-five healthy controls (CON; 7 females; 24 ± 4 y) and 13 individuals with MetSyn (5 females; 27 ± 8 y) completed this study. Subjects were unmedicated, and females were studied on days 1-5 of their menstrual cycle. A metabolic panel, blood pressure, and waist circumference were collected in a fasted state. Magnetic resonance imaging (MRI, 3 Tesla) with arterial spin labeling was used to quantify global and regional CBF. Two-way (Group x Sex) linear models with Shaffer’s correction and Tukey adjusted post hocs were used to determine differences in CBF. In the MetSyn groups, Pearson correlation coeffcients were assessed between fasting TG levels and each global and regional CBF value. Global CBF was greater in female CON compared to all groups (p ≤ 0.01), and male CON had greater CBF than male MetSyn (p = 0.03), whereas there was no difference between male and female MetSyn (p = 0.43). Regional analyses resulted in the same pattern of between-group differences in the parietal lobe (p = 0.03), the precuneus (p = 0.01), and the frontal lobe (p = 0.01), outside of a nonsignificant difference between male CON and male MetSyn in the frontal lobe (p = 0.12). No interactions existed for the temporal lobe, occipital lobe, or thalamus (p ≥ 0.06). In females with MetSyn, fasting TG levels were moderately negatively correlated with CBF (r = -0.65), whereas a moderate positive relationship existed in males with MetSyn (r = 0.71). These data suggest that MetSyn reduces CBF to a greater extent in females than males, abolishing sex-dependent differences in CBF present in healthy young adults. While female sex is protective against cardiovascular disease in healthy young adults, this is not the case in individuals with MetSyn. Additionally, males and females with MetSyn had opposing relationships between fasting TG levels and CBF. These findings may help explain the greater cardiovascular risk in females with insulin resistance. American Diabetes Association (ADA1-16-ICTS-099 and ADA 1-12-IN-39); Clinical and Translational Science Award program (UL1TR002373); Wisconsin National Primate Research Center (P51OD011106). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Structure and Function of Pancreatic Neural Circuitry in Obesity and Diabetes

INTRODUCTION: Pancreatic islets are richly innervated by autonomic nerves which contribute to physiological regulation of islet hormone release and blood glucose. Published studies suggest obesity disrupts pancreatic innervation and may contribute to metabolic dysfunction. However, these studies largely rely on 2D imaging of islets and experiments aimed at assessing the function of pancreatic nerves have not been organ specific. Determining how high-fat diet (HFD) impacts pancreatic nerve structure and function using 3D imaging and organ-specific neuromodulation may provide new insights into the pathophysiology of diabetes and identify novel therapeutic approaches to treat diabetes. METHODS: To test the hypothesis that HFD causes structural changes in pancreatic innervation, C57Bl6 mice were randomized to 1, 4 and 12 week high-fat (HFD) or low-fat diet (LFD) groups. Metabolic phenotyping was determined. Pancreata were cleared and immunolabeled using iDISCO+, imaged by lightsheet (4X) and confocal (10X) microscopy and images were analyzed using Imaris software. To test the effects of HFD on pancreatic nerve function, we used AAV8 delivery of cre-dependent neuromodulatory constructs to activate or silence pancreatic parasympathetic or sympathetic nerves. To modulate pancreatic parasympathetic nerves, we delivered cre-dependent hM3D(Gq) for activation, cre-dependent diphtheria toxin A subunit for silencing, or mCherry (control) into the pancreas of Chat-cre mice. To modulate pancreatic sympathetic nerves, we used pancreatic injection of retrograde AAV delivering cre and celiac injection of cre-dependent hM3Gq (activation), hM4Gi (silencing) or mCherry (control). Mice were fed LFD or HFD for up to 12 weeks and the effects of neuromodulation on glucose metabolism were examined. RESULTS: HFD significantly impaired glucose tolerance, insulin sensitivity and altered plasma insulin and glucagon after 1, 4 and 12 weeks of HFD consumption. HFD consumption significantly altered pancreatic neural structure. Within islets, 1 week of HFD significantly increased sympathetic neural volume. With prolonged HFD, there was significant loss of islet parasympathetic innervation. Reproducing loss of islet parasympathetic innervation impaired glucose tolerance but sympathetic activation did not alter glucose metabolism. Targeted silencing of pancreatic sympathetic innervation or activation of pancreatic parasympathetic innervation significantly improved glucose tolerance in hyperglycemic mice fed HFD. CONCLUSION: Short term HFD causes early rapid changes to islet sympathetic nerves while long term HFD consumption results in loss of pancreatic parasympathetic innervation of the islet. The effects of HFD consumption are improved by inhibiting pancreas-projecting sympathetic fibers or through activation of pancreatic parasympathetic nerves. These studies suggest modulating pancreatic innervation may improve glucose control in obesity. NIH F31 Predoctoral Fellowship (1F31DK129016-01A1, R.H.) ISMMS MSTP T32 (GM007280) NIH (R01NS097184, OT2OD024912, S.S.) American Diabetes Association (ADA #1-17-ACE-31, S.S) Department of Defense (W81XWH-20-1-0345, S.S). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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

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

Relationships between Body Composition Measurements and Insulin-Stimulated Plasma Lipoprotein Lipase Activity in Individuals with Varying Degrees of Body Adiposity

Lipoprotein Lipase (LPL) hydrolyzes plasma triglycerides into free fatty acids in the circulation for use and/or storage in tissues (i.e., adipose tissue, skeletal muscle). Impaired LPL activity (LPLa) is associated with unfavorable health outcomes, such as elevated plasma triglyceride concentrations. We sought to determine how plasma LPLa relates to body composition measurements in individuals with varying degrees of adiposity. Eighteen subjects (ages 19 to 45 years) with body mass index (BMI) between 18 and 45 kg/m2 had their body composition measured by dual-energy X-ray absorptiometry (DEXA) and insulin sensitivity estimated from an oral glucose tolerance test by using the Matsuda Index (MI). Subjects ingested a bolus of 5g fat (i.e., whipping cream, 0.2 g fat/kg fat free mass), followed by small boluses of fat over the course of a 3-hour experimental period. This experimental protocol allows for the induction of a postprandial state without perturbation of the plasma triglyceride or insulin concentrations. LPLa was measured in the presence of increased plasma insulin induced by intravenous insulin infusion during the last 30 mins of the 3-hour experimental protocol. Insulin was infused at a rate of 0.5 mU/kg/min for subjects with MI-determined insulin sensitivity &lt; 4 and 1 mU/kg/min for those with MI-determined insulin sensitivity &gt; 4, in order to produce comparable levels of plasma insulin concentrations across subjects. To release endothelial-bound LPL, subjects received an injection of intravenous heparin (75 UI/kg) at the end of the plasma insulin infusion. Plasma samples were collected 10 minutes after the heparin infusion and analyzed for LPL concentration (LPLc) and LPLa using commercially available ELISA kits. Person’s correlation was used to evaluate relationships between several body composition parameters and LPLc as well as LPLa. LPLc was not correlated (P &gt;0.05) with BMI (r = 0.03), total lean body mass (r = -0.20), total body fat (r = -0.02), or android fat (r = - 0.08). However, LPLa was positively correlated (P &lt;0.05) with BMI (r = 0.49) and total lean body mass (r = 0.58), as well as total body fat (r = 0.54, P = 0.02) and android fat (r = 0.58, P = 0.01). In conclusion, increased body fat, including android fat, are associated with increased intravascular LPLa in the presence of insulin. Greater insulin-stimulated intravascular LPLa can enhance the release of triglyceride-associated free fatty acids and their uptake by tissues, resulting in insulin resistance as documented in individuals with increased android fat distribution. American Diabetes Association Grant #7-12-CT-40. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Insulin Therapy in Ossabaw Miniature Swine with Type 1 Diabetes

Background: Therapy for type 1 diabetes resulting from immunogenic destruction of the insulin-producing pancreatic beta cells has been a challenge for over 100 years. Delivering exogenous insulin to maintain euglycemia is a delicate balance between plasma glucose transport to insulin-responsive tissues, glucose absorption in the gut, and the pharmacodynamics of insulin. The synthesis of short- and long-acting insulins and use of insulin pumps have made great strides in the standard of diabetes care. Despite advances, hypoglycemia is a major limitation. There is no approved therapy that offers glucose-responsive insulin function. Toward this end we engineered a nanoscale complex combining both electrostatic and dynamic-covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high-affnity glucose-binding motif. Hypothesis: This insulin nanocomplex will yield an injectable insulin depot providing both glucose-sensitive and long-lasting insulin availability in a translation preclinical model. Methods: Ossabaw minature swine (41-59 kg; N=6) were made diabetic with alloxan, which was confirmed by stable hyperglycemia (228±43 mg/dL). Oral glucose tolerance tests (OGTT) were conducted at the diabetic baseline and each of the following 6 days after one subcutaneous injection of the insulin nanocomplex. Results: The basline OGTT elicted blood glucose of 350-450 mg/dL for 90 min of the 150 min OGTT, while serum insulin remained at ~5 μU/mL, nearly the detection limit. In contrast, 3 h after injection of insulin nanocomplex (~0.8-0.9 mg/kg) blood glucose decreased to 71±12 mg/dL. Subsequent OGTTs on days 1-6 increased blood glucose from normoglycemia to ~200 mg/dL and serum insulin increased to ~60-220 μU/mL, followed by return to nearly normolgycemia hours after the OGTT. Hypoglycemia was avoided in all pigs. Conclusions: The subcutaneous nanocomplex of a modified insulin and a synthetic dendrimer carrier produced a glucose-responsive insulin depot for week-long glycemic control following a single routine injection. These findings offer great promise for overcoming the hypoglycemia risk of intensive glucose control. Future studies should include additional physiological challenges of exercise and nutritional states. Support: Juvenile Diabetes Research Foundation 5-CDA-2020-947-A-N, Helmsley Charitable Trust 2019PG-T1D016 and 2102-04994, American Diabetes Association Pathway 1-19-ACE-31, National Science Foundation BMAT1944875, European Union-Next Generation EU LX22NPO5104, Czech Academy of Sciences RVO 6138963. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.