Lower Incidence Of Diabetes Research Articles

Evaluating the Glycemic Effects of Dolutegravir and Its Predictors Among People With Human Immunodeficiency Virus in Uganda: A Prospective Cohort Study

Abstract Background Dolutegravir (DTG), a key component of the recommended human immunodeficiency virus (HIV) treatment regimens in Uganda, has been associated with hyperglycemia. We evaluated its influence on hyperglycemia risk to create a hyperglycemia risk stratification tool for patient monitoring. Methods We conducted a prospective cohort study at 3 sites with 628 HIV-positive patients on tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD). Participants included both nucleoside reverse transcriptase inhibitor–experienced (exposed) and antiretroviral therapy (ART)–naive (nonexposed) groups. Follow-up occurred every 6 months with random blood sugar (RBS) testing every 3 months. Participants with RBS ≥7 mmol/L were classified as hyperglycemic and underwent glycated hemoglobin (HbA1c) testing, confirming diabetes with a 6.5% cut-off. Results The study found a hyperglycemia incidence rate of 24.5 (95% confidence interval [CI], 19.3–31.1) cases per 100 person-years (PY) and a diabetes incidence rate of 5.8 cases (95% CI, 3.6–9.3) per 100 PY. Hyperglycemia incidence was slightly lower in nonexposed (20.8 cases per 100 PY) versus exposed groups (25.2 cases per 100 PY). Multivariable analysis indicated a trend toward lower hyperglycemia risk (adjusted hazard ratio [aHR], 0.78 [95% CI, .37–1.66]; P = .52) and substantially lower diabetes incidence (aHR, 0.34 [95% CI, .04–2.82]; P = .32) in the nonexposed group. Significant factors for hyperglycemia included age (P < .001), study site (P < .001), and DTG-based ART duration (P = .02). Conclusions Our study showed an increased incidence of hyperglycemia with age, study site, and duration of DTG exposure in people with HIV on TLD. We suggest integrated screening and care for hyperglycemia and diabetes in HIV services, especially when initiating DTG regimens.

Metformin in diabetes management: expanding benefits. Review

We have conducted a narrative review based on a structured search strategy, focusing on the effects of metformin on the progression of non‑diabetic hyperglycemia to clinical type 2 diabetes mellitus. The principal trials that demonstrated a significantly lower incidence of diabetes in at‑risk populations randomized to metformin (mostly with impaired glucose tolerance) were published mainly from 1999 to 2012. Metformin reduced the 3‑year risk of diabetes by ‑31% in the randomized phase of the Diabetes Prevention Program (DPP), vs.‑ 58% for intensive lifestyle intervention. Metformin was most effective in younger, heavier subjects. Diminishing but still significant reductions in diabetes risk for subjects originally randomized to these groups were present in the trial’s epidemiological follow‑up, the DPP Outcomes Study (DPPOS) at 10 years (‑18 and ‑34%, respectively), 15 years (‑18 and ‑27%), and 22 years (‑18 and ‑25%). Long‑term weight loss was also seen in both groups, with better maintenance under metformin. Subgroup analyses from the DPP/DPPOS have shed important light on the actions of metformin, including a greater effect in women with prior gestational diabetes, and a reduction in coronary artery calcium in men that might suggest a cardioprotective effect. Improvements in long‑term clinical outcomes with metformin in people with non‑diabetic hyperglycemia («prediabetes») have yet to be demonstrated, but cardiovascular and microvascular benefits were seen for those in the DPPOS who did not vs. did develop diabetes mellitus. Multiple health economic analyses suggest that either metformin or intensive lifestyle intervention is cost‑effective in a community setting. Long‑term diabetes prevention with metformin is feasible and is supported in influential guidelines for selected groups of subjects. Future research will demonstrate whether intervention with metformin in people with non‑diabetic hyperglycemia will improve long‑term clinical outcomes.

CETP and SGLT2 inhibitor combination therapy increases glycemic control: a 2x2 factorial Mendelian randomization analysis.

Cholesteryl ester transfer protein (CETP) inhibitors, initially developed for treating hyperlipidemia, have shown promise in reducing the risk of new-onset diabetes during clinical trials. This positions CETP inhibitors as potential candidates for repurposing in metabolic disease treatment. Given their oral administration, they could complement existing oral medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors, potentially delaying the need for injectable therapies such as insulin. We conducted a 2x2 factorial Mendelian Randomization analysis involving 233,765 participants from the UK Biobank. This study aimed to evaluate whether simultaneous genetic inhibition of CETP and SGLT2 enhances glycemic control compared to inhibiting each separately. Our findings indicate that dual genetic inhibition of CETP and SGLT2 significantly reduces glycated hemoglobin levels compared to controls and single-agent inhibition. Additionally, the combined inhibition is linked to a lower incidence of diabetes compared to both the control group and SGLT2 inhibition alone. These results suggest that combining CETP and SGLT2 inhibitor therapies may offer superior glycemic control over SGLT2 inhibitors alone. Future clinical trials should investigate the potential of repurposing CETP inhibitors for metabolic disease treatment, providing an oral therapeutic option that could benefit high-risk patients before they require injectable therapies like insulin or glucagon-like peptide-1 (GLP-1) receptor agonists.

Normal or improved cardiovascular risk factors in IGF-I-deficient adults with growth hormone receptor deficiency

Human subjects with generalized growth hormone (GH) insensitivity due to GH receptor deficiency (GHRD)/Laron syndrome display a very low incidence of insulin resistance, diabetes, and cancer, as well as delayed age-related cognitive decline. However, the risk of cardiovascular disease (CVD) in these subjects is poorly understood. Here, we have assessed cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. We measured markers of CVD in two phases: one in a cohort of 30 individuals (GHRD= 16, control relatives= 14) brought to USC (in Los Angeles, CA) and one in a cohort including additional individuals examined in Ecuador (where the subjects live) for a total of 44 individuals (GHRD= 21, control relatives= 23). Data were collected on GHRD and control groups living in similar geographical locations and sharing comparable environmental and socio-economic circumstances. Compared to controls, GHRD subjects displayed lower serum glucose, insulin, blood pressure, smaller cardiac dimensions, similar pulse wave velocity, lower carotid artery intima-media thickness, lower creatinine, and a non-significant but major reduction in the portion of subjects with carotid atherosclerotic plaques (7% GHRDs vs. 36%, Controls p= 0.1333) despite elevated low-density lipoprotein cholesterol levels. The current study indicates that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors as compared to their relatives. This study was funded in part by NIH/NIA grant P01 AG034906 to V.D.L.

Clinical performance of the iPREDICTLIVING tool for the prediction of the post-transplant recipient and living donor outcomes in a European cohort.

A living donor kidney transplant (LDKT) is the best treatment for ESRD. A prediction tool based on clinical and demographic data available pre-KT was developed in a Norwegian cohort with three different models to predict graft loss, recipient death, and donor candidate's risk of death, the iPREDICTLIVING tool. No external validations are yet available. We sought to evaluate its predictive performance in our cohort of 352 pairs LKDT submitted to KT from 1998 to 2019. The model for censored graft failure (CGF) showed the worse discriminative performance with Harrell's C of.665 and a time-dependent AUC of.566, with a calibration slope of.998. For recipient death, at 10 years, the model had a Harrell's C of.776, a time-dependent AUC of.773, and a calibration slope of 1.003. The models for donor death were reasonably discriminative, although with a poor calibration, particularly for 20 years of death, with a Harrell's C of.712 and AUC of.694 with a calibration slope of.955. These models have moderate discriminative and calibration performance in our population. The tool was validated in this Northern Portuguese cohort, Caucasian, with a low incidence of diabetes and other comorbidities. It can improve the informed decision-making process at the living donor consultation joining clinical and other relevant information.

Association between physical activity level and diabetes incidence among Chinese middle-aged and older adults: a cross-sectional study from the China health and retirement longitudinal study.

It has been shown that diabetes is associated with insufficient physical activity among middle-aged and older adults, but the association between different physical activity levels (PAL) and diabetes incidence needs to be further explored. This study aims to explore the correlation and dose-response relationship between different PAL and the diabetes incidence in middle-aged and older adults. Utilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), this cross-sectional analysis included 17,226 middle-aged and older adults aged 45 and above. Binary logistic regression models and restricted cubic spline (RCS) were used to explore the correlation and dose-response relationship between different PAL and the incidence of diabetes in the total middle-aged and older adults population as well as in subgroups. Sensitivity analyses were also performed to verify the robustness of the findings. In the entire study population, compared with the lowest PAL, participants in the third and fourth quartiles PAL saw diabetes incidence significantly reduced by 16% (p = 0.005) and 33% (p < 0.001), respectively (p for trend < 0.001). In subgroup analyses, the fourth quartile PAL significantly reduced the diabetes incidence among females, individuals aged 60-69, and rural residents by 25% (p = 0.011), 38% (p < 0.001) and 28% (p < 0.001), respectively. For males, middle-aged (45-59 years), and urban residents, the third quartile PAL reduced diabetes incidence by 22% (p = 0.004), 24% (p = 0.012), 21% (p = 0.013), respectively. When the fourth quartile PAL was reached, the diabetes incidence was significantly reduced in these populations by 41% (p < 0.001), 39% (p < 0.001), and 41% (p < 0.001), respectively. There was a negative dose-response relationship between physical activity and diabetes incidence in specific Chinese middle-aged and older adults population. In addition, sensitivity analyses indicated the robustness of the findings. Higher PAL was associated with lower diabetes incidence in specific Chinese middle-aged and older adults population. It is feasible to use physical activity to predict diabetes incidence in this demographic, and high PAL may be an effective means of preventing and controlling diabetes.

A low-inflammatory diet is associated with a lower incidence of diabetes: role of diabetes-related genetic risk

BackgroundWhether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes.MethodsAmong 142,271 diabetes-free UK Biobank participants (aged 39–72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7–6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression.ResultsDuring follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group.ConclusionsA low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.

Comparison of medical resources and costs among patients with coronary heart disease and impaired glucose tolerance in the Acarbose Cardiovascular Evaluation trial.

The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha-glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within-trial medical resource use and costs, and quality-adjusted life years (QALYs). Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health-related quality of life was captured using the EuroQol-5 Dimension-3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p = .009), but there were no significant differences in total inpatient days (rate ratio 1.04, p = .30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p < 0.001). QALYs reported by participants in the acarbose arm (3.96 QALYs) were marginally higher than in the placebo arm (3.95 QALYs), but the difference was not statistically significant (0.01 QALYs; p = .58). Acarbose, compared with placebo, participants cost more due to study drug costs and reported no statistically significant difference in QALYs. These higher within-trial costs could potentially be offset in future by savings from the acarbose-related lower incidence of diabetes.

Effects of Obesity Type on Diabetes and Hypertension in Obese Korean Adults

Obesity is a major cause of diabetes and hypertension. Previous studies have analyzed the effects of obesity on diabetes and hypertension by comparing non-obese and obese groups. Here, we investigated the effects of obesity type through comparison between obesity types in obese adults.The sample comprised 8,914 adults, classified as obese according to body mass index criteria or waist circumference criteria, selected from the Korean National Health and Nutrition Examination Survey (2016-2020). Obesity was classified as abdominal obesity-only, general obesity-only, and abdominal and general obesity. The effects of obesity type on diabetes and hypertension were analyzed using logistic regression model.12.78% of participants exhibited abdominal obesity-only, 22.35% had general obesity-only, and 64.78% had both types. The proportion of patients aged ≥60 years was 57.52% in the abdominal obesity-only group, while 17.12% in the general obesity-only group. The general obesity-only group had a lower incidence of diabetes than the abdominal obesity-only group (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.47-0.77), and the abdominal and general obesity group had a higher incidence of hypertension than the abdominal obesity-only group (OR, 1.82; 95% CI, 1.54-2.15).Abdominal obesity has a stronger association with diabetes than general obesity, and the risk of hypertension is greatest when both obesity types coexist. Individuals with abdominal obesity-only are likely to be excluded from obesity management, especially when aged ≥60 years. The risk of hypertension is much greater when abdominal and general obesity coexist, emphasizing the need to use both body mass index and waist circumference to define obesity.

Lipoprotein(a), metabolic profile and new-onset type 2 diabetes in patients with familial combined hyperlipidemia: A 9 year follow-up study

Lipoprotein(a) [Lp(a)] appears to have an inverse association with the risk of type 2 diabetes mellitus in the general population. This study aimed to investigate the prognostic role of Lp(a) regarding the development of type-2 diabetes in the special population of subjects with familial combined hyperlipidemia (FCH). This cohort study included 474 patients (mean age 49.7±11.3 years, 64% males) with FCH, without diabetes at baseline who were followed for a mean period of 8.2±6.8 years. At baseline evaluation venous blood samples were obtained for the determination of lipid profile and Lp(a) levels. The endpoint of interest was the development of diabetes. Patients with increased Lp(a) levels ≥30mg/dl compared to those with low Lp(a) levels <30mg/dl had lower levels of triglycerides (238±113 vs 268±129 mg/dl, p=0.01), greater levels of high-density lipoprotein (HDL) cholesterol (44±10 vs 41±10 mg/dl, p=0.01) and hypertension in a greater percentage (42% vs 32%, p=0.03). The incidence of new-onset diabetes during the follow-up period was 10.1% (n=48). Multiple Cox regression analysis revealed that increased Lp(a) is an independent predictor of lower diabetes incidence (HR 0.39, 95% CI 0.17-0.90, p=0.02) after adjustment for confounders. Among subjects with FCH those with higher Lp(a) levels have lower risk for the development of type 2 diabetes. Moreover, the presence of increased Lp(a) seems to differentiate the expression of metabolic syndrome characteristics in patients with FCH, as increased Lp(a) is related to lower levels of triglycerides, greater prevalence of hypertension and higher levels of HDL cholesterol.

Influencing factors of early dramatic recovery of neurological function after intravenous thrombolysis in patients with branch atheromatous disease.

Intravenous thrombolysis can significantly improve the neurological function of patients with acute ischemic stroke. However, the expected early dramatic recovery (EDR) of neurological function after thrombolysis is not achieved in some patients with branch atheromatous disease (BAD). Here we evaluated the factors associated with EDR after thrombolysis in BAD patients. We conducted a retrospective study on 580 consecutive BAD patients. All patients met the diagnostic criteria of BAD and received intravenous recombinant tissue-type plasminogen activator (rt-PA). EDR was defined when the improvement of National Institutes of Health Stroke Scale (NIHSS) score was >8 points within 2 or 24 hours after rt-PA, or the total NIHSS score was 0 or 1. The factors associated with EDR were analyzed with multivariate logistic regression analysis. Among 580 patients, the incidence of EDR was 35.2% (204 cases). Compared with patients without EDR, patients with EDR had lower incidence of diabetes (15.7% vs 29.3%, P < .001), lower NIHSS scores at 2 and 24 hours after rt-PA (P < .001), less cerebral hemorrhage (0% vs 5.3%, P = .001), and shorter onset to treatment time (OTT) (P < .001). Multivariate logistic regression analysis in propensity score-matched cohort showed that EDR was associated with OTT (adjusted OR = 0.994; 95% CI, 0.989-0.999) and NIHSS score after rt-PA (adjusted OR = 0.768; 95% CI, 0.663-0.890). Notably, diabetes (adjusted OR = 0.477, 95% CI, 0.234-0.972) was an independent factor related to EDR of neurological function in BAD patients. In the subgroup analysis, a lower incidence of diabetes (adjusted OR = 0.205, 95% CI: 0.059-0.714, P = .013) and a lower NIHSS score after thrombolysis in patients with paramedian pontine infarction (adjusted OR = 0.809, 95% CI: 0.656-0.997, P = .047) were significantly associated with EDR. Diabetes is not conducive to EDR of neurological function in patients with BAD, especially in patients with paramedian pontine infraction. Low NIHSS score and short OTT after thrombolysis may be closely related to EDR after intravenous thrombolysis.

Analysis of inpatient complications in HIV/AIDS patients undergoing total hip arthroplasty – A propensity matched cohort study

Patients with human immunodeficiency virus (HIV) are at higher risk for orthopedic related diseases due to dysregulation in bone metabolism and metabolic effects related to their medication regimen. Furthermore, the rate of hip arthroplasty in HIV patients is increasing. With the recent changes in THA methodologies and improvements in HIV treatment, there is a need for updated research analyzing hip arthroplasty outcomes in this high-risk patient population. In this study, we used a national database to evaluate postoperative outcomes in HIV patients undergoing THA compared to THA patients without HIV. We use a propensity algorithm to create a cohort of 493 HIV negative patients for matched analysis. Among the 367,894 THA patients included in this study, 367,390 patients were HIV negative and 504 were HIV positive. The HIV cohort had a lower mean age (53.34 vs 65.88, p < 0.001), lower proportion of females (44% vs 76.4%, p < 0.001), lower incidence of diabetes without complications (5% vs 11.1%, p < 0.001) and a lower incidence of obesity (0.544 vs 0.875, p = 0.002). In the unmatched analysis, the incidence of acute kidney injury (4.8% vs 2.5%, p = 0.004), pneumonia (1.2% vs 0.2%, p = 0.002), periprosthetic infection (3.6% vs 1%, p < 0.001), and wound dehiscence (0.6% vs 0.1%, p = 0.009) were higher in HIV cohort, most likely due to inherent demographic variances present in the HIV population. In the matched analysis, the rates of blood transfusion (5.0% vs 8.3%, p = 0.041) were lower in the HIV cohort. Other post-operative variables, such as rates of pneumonia, wound dehiscence, and surgical site infections were not statistically significant between the HIV positive population and HIV negative matched cohort. Our study found similar rates of postoperative complications in HIV positive and HIV negative patients. The rate of blood transfusions in HIV positive patients was also noted to be lower. Our data suggests that THA is a safe procedure in patients infected with HIV.

Pre-morbid Risk Factor Control Differences by Age in Patients Undergoing Thrombectomy for Acute Ischemic Stroke (P8-5.014)

<h3>Objective:</h3> We proposed to estimate the percentage of large vessel strokes that are potentially attributable to unmanaged vascular risk factors and how this may differ by age to improve stroke prevention and patient outcomes. <h3>Background:</h3> Controlling metabolic and behavioral risk factors may avert 75% of the world stroke burden. We anticipate risk factors, and their management may differ depending on age of patient and may offer insight into preventative strategies. <h3>Design/Methods:</h3> A retrospective chart review was conducted on patients undergoing endovascular therapy from 2012–2019 at University of Maryland. Patients were stratified based on age into three groups: &lt;50, 50–70, and &gt;70 years of age. Risk factors prior to admission including hypertension, diabetes, hyperlipidemia, atrial fibrillation, history of vascular disease, and current smoking were recorded. A possibly preventable stroke was defined as having a history of at least one of these risk factors that was not being optimally controlled according to current guidelines. Chi squared tests of proportion were used to evaluate differences between age groups. <h3>Results:</h3> 396 patients underwent thrombectomy (50% female, mean age 64.7). The most prominent etiology of stroke across all age groups was cardioembolic. 62% of strokes in patients &lt;50 years of age were preventable as compared to 82% in patients 50–70 years old and 79% in patients older than 70. Smoking was a common risk factor in all age groups. Despite overall lower incidence of diabetes and hyperlipidemia in patients &lt;50 with stroke, a large proportion of these patients presented with poor control of these risk factors (p=0.04 and p=0.01). <h3>Conclusions:</h3> Most patients who underwent thrombectomy had at least one cardiovascular risk factor that was uncontrolled despite age group. This illustrates the importance of cardiovascular risk factor management in primary prevention of stroke, especially control of diabetes and hyperlipidemia in the younger population. <b>Disclosure:</b> Dr. Grimes has nothing to disclose. Dr. Mehndiratta has nothing to disclose. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Chaturvedi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Calgary. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Ramar &amp; Paradiso. Dr. Chaturvedi has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cole, Scott, Kissane. The institution of Dr. Chaturvedi has received research support from NINDS.

A Diet Producing a Low Diabetes Incidence Modifies Immune Abnormalities in Diabetes-Prone BB Rats

The effect of feeding a diet that produces a high or low incidence of diabetes on immune abnormalities proposed to contribute to the pathogenesis of autoimmune-mediated diabetes was investigated. Diabetes-prone (BBdp) and nondiabetes-prone (BBn) BB rats (21 d) were fed for 21 d a nonpurified (high incidence) or purified (low diabetes incidence) diet. Compared with BBn, immune cells from spleen and mesenteric lymph nodes of BBdp rats demonstrated higher rates of metabolite production from glucose and glutamine, higher splenic cytotoxicity (lysis of 51Cr-labeled YAC-1 cells) and lower mitogen responses (3H thymidine uptake). Bypassing the membrane, using the mitogen phorbol myristate acetate + lonomycin, improved the BBdp mitogen response, suggesting a membrane defect. Immune cells from BBdp rats fed the purified, compared with the nonpurified, diet had lower rates of glutamine (spleen) and glucose (lymph nodes) metabolism and lower splenic cytotoxic activity. Although diet altered the proportion of T and B cells in lymph nodes of BBdp rats, it did not correct the abnormal lymphocyte distribution or effect mitogen responses. Feeding the purified, compared with nonpurified, diet to BBn rats altered energy metabolism by lymph node cells and resulted in lower splenic cytotoxic activity. Reduced splenic natural killer cell activity and decreased immune cell metabolism are unlikely the mechanism for the preventative effect of feeding a purified diet to BBdp rats but are indicative of reduced immune activity.

Comorbidity and Cancer Disease Rates among Those at High-Risk for Alzheimer's Disease: A Population Database Analysis.

(1) Importance: Alzheimer's disease (AD) is complex and only partially understood. Analyzing the relationship between other more treatable or preventable diseases and AD may help in the prevention and the eventual development of treatments for AD. Risk estimation in a high-risk population, rather than a population already affected with AD, may reduce some bias in risk estimates. (2) Objective: To examine the rates of various comorbidities and cancers in individuals at high-risk for AD, but without a clinical diagnosis, relative to individuals from the same population with normal AD risk. (3) Design, Setting, and Participants: We conducted a study using data from the Utah Population Database (UPDB). The UPDB contains linked data from the Utah Cancer Registry, Utah death certificates, the Intermountain Health patient population, and the University of Utah Health patient population. Subjects were selected based on the availability of ancestral data, linked health information, and self-reported biometrics. (4) Results: In total, 75,877 participants who were estimated to be at high risk for AD based on family history, but who did not have an active AD diagnosis, were analyzed. A lower incidence of diabetes (RR = 0.95, 95% CI [0.92,0.97], p < 0.001), hypertension (RR = 0.97, 95% CI [0.95,0.99], p < 0.001), and heart disease (RR = 0.95, 95% CI [0.93,0.98], p < 0.001) was found. There was no difference in rates of cerebrovascular disease or other forms of dementia. Of the 15 types of cancer analyzed: breast (RR = 1.23, 95% CI [1.16, 1.30], p < 0.001); colorectal (RR = 1.30, 95% CI [1.21, 1.39], p < 0.001); kidney (RR = 1.49, 95% CI (1.29, 1.72), p < 0.001); lung (RR = 1.25, 95% CI [1.13, 1.37], p < 0.001); non-Hodgkin's Lymphoma (RR = 1.29, 95% CI [1.15, 1.44], p < 0.001); pancreas (RR = 1.34, 95% CI [1.16, 1.55], p < 0.001); stomach (RR = 1.59, 95% CI [1.36, 1.86], p < 0.001); and bladder (RR = 1.40, 95% CI [1.25, 1.56], p < 0.001), cancers were observed in significant excess among individuals at high-risk for AD after correction for multiple testing. (5) Conclusions and Relevance: Since age is the greatest risk factor for the development of AD, individuals who reach more advanced ages are at increased risk of developing AD. Consistent with this, people with fewer comorbidities earlier in life are more likely to reach an age where AD becomes a larger risk. Our findings show that individuals at high risk for AD have a decreased incidence of various other diseases. This is further supported by our finding that our high-risk group was also found to have an increased incidence of various cancers, which also increase in risk with age. There is the possibility that a more meaningful or etiological relationship exists among these various comorbidities. Further research into the etiological relationship between AD and these comorbidities may elucidate these possible interactions.

Prevalence and Characteristics of Patients with Median Arcuate Ligament Syndrome in a Cohort Diagnosed with Celiac Artery Compression.

Median arcuate ligament syndrome (MALS) is a frequent differential diagnosis in patients with postprandial abdominal symptoms, but diagnosis remains challenging. The aim of this study was to identify characteristics of patients who had MALS compared with non-MALS patients among a cohort of patients diagnosed with celiac artery compression (CAC). An IRB-approved retrospective chart review (2000 to 2021) of patients at our institution with a discharge diagnosis of CAC was performed. Medical record review for clinical symptoms and findings consistent with MALS was performed. Two hundred ninety-three patients with a diagnosis of CAC were identified; 59.7% were women, and average age was 63.9 ± 20.2 years. Sixty-nine (23.5%) patients with CAC had MALS. There were no significant differences in sex or race between MALS and non-MALS patients, but MALS patients were younger (55.7 vs 68.1, p < 0.001). There was no significant difference in gastrointestinal comorbidities between the 2 groups. Patients with MALS were less likely to have diabetes (12.5% vs 26.9%), renal disease (4.6% vs 8.2%), hypertension (41.5% vs 70.3%), mesenteric atherosclerotic disease (14% vs 61.9%), and peripheral artery disease (15.0% vs 39.7%). We demonstrate a novel observation that MALS patients tend to have fewer atherosclerotic characteristics than non-MALS patients with CAC. Patients in our study with MALS were more likely to be younger, women, and presenting with epigastric pain. MALS patients had a significantly lower incidence of diabetes, hypertension, renal disease, mesenteric artery disease, and peripheral arterial disease compared with the non-MALS group. An important clinically relevant feature of MALS patients may be their lack of atherosclerotic phenotype compared with non- MALS patients with CAC.

Centurion Livers: Making It to 100 with a Transplant

INTRODUCTION: Liver senescence is not as marked as other solid organs and offers the potential for older allografts to survive for extended periods post-transplant. Livers with a total age of greater than 100 years are known to exist but have not been studied. We examined the characteristics and outcomes of all liver allografts with a cumulative age of greater than 100 years. METHODS: Using the United Network for Organ Sharing (UNOS) STAR file, donor livers with a cumulative age (sum of initial age at transplant plus post-transplant survival) of at least 100 years (CENTURION) were identified from all transplants between 1990 and 2022. Donor/recipient demographic data and outcomes data were collected and compared with all other transplants. RESULTS: Twenty-five of 253,406 transplanted livers met criteria for the CENTURION group. Although significantly older (84.7 vs 38.5 years), CENTURION donors had lower transaminases, lower incidence of diabetes, and fewer donor infections. CENTURION recipients had significantly lower Model for End-stage Liver Disease (MELD) score at the time of transplant. No CENTURION grafts were lost to primary nonfunction or vascular/biliary complications. Interestingly, there was no significant difference in rates of rejection at 12 months. CENTURION outcomes had significantly better allograft (p = 0.0079) and patient survival (p = 0.0077; Fig. 1).Figure 1CONCLUSION: The existence of allografts more than 100 years old is revealing of the dramatic resilience of the liver to senescent events. Further clinical studies to increase understanding and promote use of older donors should be encouraged. Specifically target studies of donor livers with proven longevity could offer new insight into genetic and biological factors inherent in these resilient allografts.

Lipoprotein (a) and new-onset type-2 diabetes in patients with familial combined hyperlipidemia: a 9 years follow-up study

Abstract Background Elevated lipoprotein(a) [Lp(a)] levels have been related with increased cardiovascular (CV) risk in the general population. However, its relationship with type-2 diabetes and CV risk in patients with Familial Combined Hyperlipidemia (FCH) is rather unclear. Thus, the aim of our study was to investigate the prognostic role of Lp(a) regarding new-onset type-2 diabetes and major adverse cardiovascular outcomes in patients with FCH. Methods 485 patients from the outpatient lipid clinic of our hospital (301 males,mean age 49.8±10.8 years, 35%smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FCH criteria participated in the study. Participants were evaluated for a mean follow-up period of 8.9±7.5 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile, and levels of Lp(a). All subjects were on lipid-lowering medication (statin and ezetimibe or fibrate) during the follow-up period. The endpoints of our study was new-onset diabetes and the composite of major CV events (coronary artery disease events and stroke). Results The incidence of new-onset diabetes during the follow-up period was 10% (n=42). The group of patients with new-onset diabetes (n=42) had lower levels of Lp(a) at baseline compared to those without new-onset diabetes (n=376) (23.8±19.2 vs 32.9±39.5 mg/dl, p=0.01). Also, those with new-onset diabetes had a lower percentage of increased Lp(a) levels (≥30 mg/dl) at baseline compared to those without new-onset diabetes (21% vs 34%). Multiple Cox regression analysis revealed that increased Lp(a) (≥30 mg/dl) is an independent predictor of lower diabetes incidence during the follow-up period (HR 0.39, 95% CI 0.17–0.90), after adjustment for confounding factors. Moreover, the incidence of new-onset CV events in the total population was 6.4% (n=31).In the group of patients with increased Lp(a) levels at baseline (≥30 mg/dl, n=159, 33%) there was a trend towards a greater incidence of CV events during the follow-up period, compared to the group of patients with lower Lp(a) levels (&amp;lt;30 mg/dl, n=326, 67%), although the difference between the two groups was not statistically significant (8.8% vs 5.1%, p=0.1). Conclusions In patients with FCH, increased baseline Lp(a) is an independent predictor of lower incidence of new-onset type-2 diabetes after an almost 9 years follow-up period. Moreover, increased Lp(a) seems to convey an increased CV risk also in patients with FCH. Funding Acknowledgement Type of funding sources: None.

Differences in the Association of Select Dietary Measures With Risk of Incident Type 2 Diabetes.

To evaluate associations between a broad range of approaches to classifying diet and incident type 2 diabetes in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. This study included 8,750 Black and White adults without diabetes at baseline. Diabetes was defined according to fasting glucose ≥70 mmol/L, random glucose ≥111 mmol/L, or use of diabetes medications. The exposures were diet scores for Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND), dietary inflammatory index (DII), dietary inflammation score (DIS), and empirical dietary patterns (plant-based and Southern) determined using data collected with use of the Block98 food-frequency questionnaire. Modified Poisson regression was used to assess association of dietary measures with risk of incident type 2 diabetes, with models adjusted for total energy intake, demographics, lifestyle factors, and waist circumference. There were 1,026 cases of incident type 2 diabetes during follow-up (11.7%). Adherence to the Southern dietary pattern was most strongly associated with risk of incident type 2 diabetes after adjustment for demographics and lifestyle (quintile [Q]5 vs. lowest Q1: risk ratio [RR] 1.95; 95% CI 1.57, 2.41). Of the diet scores, DIS (Q5 vs. Q1 RR 1.41) and MIND (Q1 vs. Q5 RR 1.33), demonstrated anti-inflammatory diets, had strongest associations with lower diabetes incidence. We found associations of several dietary approaches with incident type 2 diabetes. Investigation into mechanisms driving the association with the Southern dietary pattern is warranted. Further research into use of DIS, DII, and MIND diet score should be considered for dietary recommendations for diabetes prevention.

Association between vitamin D deficiency and the risk of prevalent type 2 diabetes and incident prediabetes: A prospective cohort study using data from The Irish Longitudinal Study on Ageing (TILDA).

SummaryBackgroundIt is hypothesized that vitamin D contributes to the aetiology of type 2 diabetes mellitus (diabetes). This study's objective was to examine the relationships between baseline vitamin D status (as measured by plasma 25-hydroxyvitamin D concentration) and both prevalent diabetes and prospective risk of developing diabetes, including prediabetes, in a population with historically low levels of vitamin D.MethodsIn this prospective cohort study, data from The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of adults aged ≥50 years residing in Ireland were analysed, including wave 1 (October 2009–June 2011) (n = 5272) and wave 3 (March 2014–October 2015) (n = 3828). Those aged <50 years at baseline or who did not complete the health assessment were excluded. Logistic regression models examined the associations between baseline vitamin D concentration (nmol/L) with prevalent diabetes status and incident diabetes/prediabetes collected at a 4-year follow-up. Models were adjusted for age, sex, education, body mass index, smoking history, physical activity, use of statins, and the season in which the vitamin D concentration was sampled.FindingsDeficient baseline vitamin D concentration was cross-sectionally associated with an increased likelihood of having prevalent diabetes (Relative Risk Ratio [RRR] 1·5, 95% CI: 1·03, 2·18; p = 0·037). In longitudinal analyses evaluating diabetes status 4 years later, there was a 62% increased likelihood (RRR: 1·62, 95% CI: 1·12, 2·35; p = 0·011) of developing prediabetes for those with vitamin D <30 nmol/L compared to those with ≥75 nmol/L. The rate of progression from prediabetes to diabetes between wave 1 and 3 was observed to be 32·5%.InterpretationThose with lower concentrations of vitamin D, as measured by 25-hydroxyvitamin D, may have different risk profiles with regards to their glycaemic status. Our study had limited power due to the low incidence of diabetes but showed strong associations with incident prediabetes, so further research is required. Optimising vitamin D status at a population level may significantly reduce diabetes.FundingTILDA is funded by Atlantic Philanthropies, the Irish Department of Health, and Irish Life, while additional funding was provided by the Irish Department of Agriculture, Food and the Marine (13F492) to cover the cost of 25-hydroxyvitamin D analysis.