Type 2 Diabetes Complications Research Articles

Cognitive Complications of Type 1 Diabetes: A Narrative Review Study

Background and Objectives Type 1 diabetes (T1D), which is generally known as insulin-dependent diabetes, is caused by insulin deficiency due to the destruction of pancreatic beta cells of the immune system and usually occurs in the early stages of life.The aim of this study was to investigate cognitive disorders caused by type 1 diabetes. Subjects and Methods In this review study, the studies on functional and cognitive complications of T1D were searched in Google Scholar and PubMed databases using the keywords type 1 diabetes, cognitive function, hyperglycemia, hypoglycemia, physical activity, nutrition, and glycemic control. Results The findings indicated the possibility of cognitive complications in people with T1D in all ages, and the severity and risk of these complications are related to aging and the presence of diabetic complications such as hyperglycemia and hypoglycemia in the long term. Conclusion It is recommended to use cognitive-behavioral interventions, improve nutrition and physical activity, and use blood sugar monitoring and control, along with drug treatment, to prevent or improve cognitive complications in T1D patients.

Foot drop in children with newly diagnosed type 1 diabetes: three case reports.

The etiology of foot drop is diverse from various diseases to mechanic injuries and includes neuropathy of the peroneal nerve. Peroneal neuropathy might also be one of the forms of diabetic neuropathy, very rarely reported as the first sign of diabetes. We describe three cases of children with newly diagnosed type 1 diabetes (TID) who developed unilateral peroneal nerve palsies and tibial nerve palsies, presenting clinically as a foot drop. In two of our cases, the symptoms of foot drop occurred shortly after starting treatment for severe diabetes ketoacidosis. In the third patient, food drop was a reason for the initial medical consultation, but eventually, TID was diagnosed. The presented cases highlight that neuropathy can be observed not only as a chronic complication of T1D, but it can also appear at the time of disease manifestation. The incorrect position of the lower limb during a keto coma may contribute to the development of neuropathy. Neuropathy can be observed not only as a chronic complication of type 1 diabetes (T1D), but it can also appear at the time of disease manifestation. The incorrect position of the lower limb causing external pressure during a keto coma may contribute to the development of neuropathy. It is important to examine the glycemia in patients with acute peroneal neuropathy, as this kind of peripheral neuropathy can be associated with newly diagnosed T1D. Normalization of glycemia might lead to rapid neuronal recovery.

Characterization of direct and/or indirect genetic associations for multiple traits in longitudinal studies of disease progression.

When quantitative longitudinal traits are risk factors for disease progression and subject to random biological variation, joint model analysis of time-to-event and longitudinal traits can effectively identify direct and/or indirect genetic association of single nucleotide polymorphisms (SNPs) with time-to-event. We present a joint model that integrates: (1) a multivariate linear mixed model describing trajectories of multiple longitudinal traits as a function of time, SNP effects, and subject-specific random effects and (2) a frailty Cox survival model that depends on SNPs, longitudinal trajectory effects, and subject-specific frailty accounting for dependence among multiple time-to-event traits. Motivated by complex genetic architecture of type 1 diabetes complications (T1DC) observed in the Diabetes Control and Complications Trial (DCCT), we implement a 2-stage approach to inference with bootstrap joint covariance estimation and develop a hypothesis testing procedure to classify direct and/or indirect SNP association with each time-to-event trait. By realistic simulation study, we show that joint modeling of 2 time-to-T1DC (retinopathy and nephropathy) and 2 longitudinal risk factors (HbA1c and systolic blood pressure) reduces estimation bias in genetic effects and improves classification accuracy of direct and/or indirect SNP associations, compared to methods that ignore within-subject risk factor variability and dependence among longitudinal and time-to-event traits. Through DCCT data analysis, we demonstrate feasibility for candidate SNP modeling and quantify effects of sample size and Winner's curse bias on classification for 2 SNPs identified as having indirect associations with time-to-T1DC traits. Joint analysis of multiple longitudinal and multiple time-to-event traits provides insight into complex traits architecture.

Large scale application of the Finnish diabetes risk score in Latin American and Caribbean populations: a descriptive study.

The prevalence of type 2 diabetes (T2D) continues to increase in the Americas. Identifying people at risk for T2D is critical to the prevention of T2D complications, especially cardiovascular disease. This study gauges the ability to implement large population-based organized screening campaigns in 19 Latin American and Caribbean countries to detect people at risk for T2D using the Finnish Diabetes Risk Score (FINDRISC). This cross-sectional descriptive analysis uses data collected in a sample of men and women 18 years of age or older who completed FINDRISC via eHealth during a Guinness World Record attempt campaign between October 25 and November 1, 2021. FINDRISC is a non-invasive screening tool based on age, body mass index, waist circumference, physical activity, daily intake of fruits and vegetables, history of hyperglycemia, history of antihypertensive drug treatment, and family history of T2D, assigning a score ranging from 0 to 26 points. A cut-off point of ≥ 12 points was considered as high risk for T2D. The final sample size consisted of 29,662 women (63%) and 17,605 men (27%). In total, 35% of subjects were at risk of T2D. The highest frequency rates (FINDRISC ≥ 12) were observed in Chile (39%), Central America (36.4%), and Peru (36.1%). Chile also had the highest proportion of people having a FINDRISC ≥15 points (25%), whereas the lowest was observed in Colombia (11.3%). FINDRISC can be easily implemented via eHealth technology over social networks in Latin American and Caribbean populations to detect people with high risk for T2D. Primary healthcare strategies are needed to perform T2D organized screening to deliver early, accessible, culturally sensitive, and sustainable interventions to prevent sequelae of T2D, and reduce the clinical and economic burden of cardiometabolic-based chronic disease.

1461-P: HbA1c-Independent Association between DNA Methylation (DNAm) and 28-Year Risk of Microvascular Complications in Type 1 Diabetes (T1D)

DNAm has been associated with microvascular disease but the few epigenome-wide association studies (EWAS) of complications in T1D were largely cross-sectional with limited data on glycemic exposure. We thus performed separate EWAS of 28-yr overt nephropathy (ON) and proliferative retinopathy (PR) risk to determine whether DNAm associations are independent of concurrent HbA1c or differ by long-term HbA1c trajectory in the Pittsburgh Epidemiology of Diabetes Complications study of childhood onset (<17 yrs) T1D (baseline mean age 29, T1D duration 21 yrs). After quality control, baseline whole blood DNAm (Illumina EPIC array) at 683,597 CpGs was analyzed in Cox models for time-to-ON (albumin excretion rate >200µg/min in ≥2 of 3 timed urines, n=306 free of ON at baseline) and PR (ETDRS grade≥60 or laser photocoagulation, n=265 free of PR), adjusting for T1D duration, sex, smoking pack-years, est. blood cell composition, and technical covariates. Additional EWAS further adjusted for baseline HbA1c. CpGs with false discovery rate (FDR) <0.20 were examined by previously derived latent HbA1c trajectory (Low: stable 7-8%, Improved: 10% decreasing to 7%, Intermediate-High: stable 9%-11%). Over 28 yrs, 65 (21.2%) developed ON; 139 (52.5%) PR. For ON, DNAm at cg19693031 (TXNIP) was associated (β per 5% DNAm=−0.43±0.09, p=2.84E-07, FDR=0.19) but attenuated in a baseline HbA1c-adjusted EWAS (β=−0.32±0.08, p=7.76E-05, FDR=0.98). For PR, 3 CpGs (cg27512687 [KIF16B]; cg04202206 [ISCA1]; cg14678509 [intergenic]) had FDR<0.20; only cg27512687 remained so after HbA1c adjustment (β=−2.6±0.49, p=8.46E-08, FDR=0.06). There was no interaction with baseline HbA1c (p=0.49); the magnitude of the cg27512687-PR association was similar regardless of HbA1c trajectory. Thus, further study of cg27512687 in KIF16B, a locus encoding a kinesin involved in receptor recycling/degradation, is warranted as it may make an HbA1c-independent contribution to PR risk T1D. Disclosure R.G.Miller: None. J.Mychaleckyj: None. S.Onengut-gumuscu: None. T.J.Orchard: None. T.Costacou: None. Funding American Diabetes Association (1-19-JDF-109 to R.G.M.); National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034818)

1327-P: The Association between Adherence to Mediterranean Dietary Pattern and Nephropathy in Long-Duration Type 1 Diabetes

Vascular complications contribute to the high morbidity and mortality in type 1 diabetes (T1D), necessitating a search for new therapeutic measures. The Alternative Mediterranean diet score (aMED), high in vegetable, fruits, legumes, whole grains, nuts, and low in red and processed meat and uses olive oil as the main fat source, has been shown to improve glycemic control and reduce cardiovascular disease (CVD) risk in type 2 diabetes, but has not been examined for relationships to vascular complications in T1D. We examined the cross-sectional relationships between aMed adherence and vascular complications among 645 individuals of the Joslin 50-year Medalist study having T1D > 50 years and food frequency histories captured. In multivariable logistic regression models adjusting for age and sex, a higher adherence to a Mediterranean diet was associated with a 17% reduced odds of diabetic nephropathy (DN, eGFR <60 ml/min/1.73m2) [OR 0.83, 95% Cl 0.72-0.95, p=0.008], and this remained significant (p<0.05) after further adjustments for HbA1c, diabetes duration, lipids and blood pressure. There were no significant associations between aMed and CVD, diabetic retinopathy or neuropathy. Among the specific aMED components, higher intake of nuts, higher ratio of monounsaturated fat to saturated fat and lower intake of red and processed meats were all associated with significantly (p<0.05) reduced odds of DN. Triglycerides, HDL and albumin-creatinine ratio (ACR) were significant effect modifiers (p for interaction <0.05) such that, more DN-protective effects of aMed were observed among those with higher triglycerides, lower HDL, and higher ACR. To conclude, our findings suggest that greater adherence to a Mediterranean diet in individuals with long duration T1D is associated with lower risk of DN, independent of traditional risk factors. Further studies are warranted to validate its potential as an effective therapeutic approach against DN in people with T1D. Disclosure A.Hayes: None. G.L.King: Research Support; Janssen Research & Development, LLC. H.Shah: None. S.Jangolla: None. J.Gauthier: None. N.A.Ziemniak: None. I.Wu: None. K.Lau: None. A.Adam: None. F.Hu: None. F.K.Tabung: None. Funding Nunnally Foundation Inc.; Thomas J. Beatson, Jr. Foundation

224-LB: Shared Genetic Architecture of Complication of Diabetes

Introduction: Approximately 1 in 10 Americans have diabetes (~37 million), 90-95% of which is type 2 diabetes (T2D). T2D is the leading cause of kidney disease (DKD), retinopathy, neuropathy, peripheral vascular disease (PVD), stroke, and coronary heart disease (CHD). Inherited variation is known to contribute to the risk of T2D complications, however, the relationship between and role of genetic variants on risk across complications is not fully understood. Method: We used data from our recently completed genomic investigations of a broad set of 18 diabetic complications, which included ~64K T2D subjects across five race-ethnic groups (Admixed Americas-, African-, East Asian-, European- and South Asian-ancestry samples) from 24 studies retrieved from dbGaP and UKBB biomedical repositories. Using these GWAS summary statistics, we calculated the genetic correlation between complication pairs with Z-scores (beta/SE) to investigate their relationship and guide post hoc pleiotropy analysis. Results: Genetic correlation analysis revealed four clusters of complications that shared strong correlation. Pleiotropy analysis identified three novel pleiotropic loci for T2D complications at SNX17 (Albuminuria, CHD & PVD), UBE2E2 (Albuminuria & end-stage kidney disease) and GCKR (Albuminuria, DKD, retinopathy, fatty liver disease, CHD & PVD). Conclusion: These findings support the hypothesis of shared heritability between diabetic complications. Additional work is needed to increase genetic discovery of pleiotropic variants across diabetic complications. Disclosure R. M. Salem: Other Relationship; Travere Inc. S. Cao: None. E. L. Richard: None. Funding Foundation for the National Institutes of Health; National Institutes of Health (R00HL122515)

1448-P: Diabetes-Related Complications and Comorbid Conditions in Older Adults with Type 1 Diabetes (T1D) in a Large Geographically Diverse Health Care System

Older adults (age 65+) with T1D are an understudied population. Though many older adults may have long-standing diabetes and the prevalence of multimorbidity accumulates over the lifespan, the prevalence of diabetes-related complications and comorbid conditions in older adults with T1D have not been well-characterized, though these factors can affect quality of life. We analyzed electronic health record (EHR) data from older adults with T1D within a large public hospital system (n=560). We used ICD-10 diagnostic codes and calculated the proportion of the sample with different comorbidities and diabetes-related complications, as well as the average number of total complications and the Charlson Comorbidity Index Score (Table). The mean number of T1D-related complications was 3.93 with 29.6% (n=166) having 6+ concurrent T1D complications. The most common T1D complication was retinopathy or other ophthalmic complication with (72%; n=402). The median Charlson Comorbidity index score was 3. Nearly half of the sample (n=282; 50.4%) had cardiovascular disease and more than one third (n=197; 35%) had renal disease. These data underscore a high burden of diabetes complications and comorbidities among older adults with T1D. Understanding the medical complexity of this population can inform future research and intervention. Disclosure A.Kahkoska: None. J.M.Weinstein: Research Support; Dexcom, Inc. R.Muthukkumar: None. L.A.Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Eli Lilly and Company, Jaeb Center for Health Research, Sanofi, Boehringer-Ingelheim. Funding National Institutes of Health (KL2TR002490, UL1TR002489)

1169-P: A Systematic Review of the Effects of Provider Bias on Outcomes in Youth and Young Adults with Type 1 Diabetes

Background: There are significant and pervasive inequities in the health outcomes of youth and young adults with type 1 diabetes (T1D). This review sought to examine 1) child and caregiver demographic and biopsychosocial variables associated with provider bias and outcomes (e.g., HbA1c; blood glucose values and range; diabetes technology use; burnout, stress, anxiety associated with T1D care); 2) evidence for associations between experiences of provider bias and patient physical and psychological outcomes; and 3) evidence for mediators or moderators (e.g., socioeconomic status, race/ethnicity) contributing to the association between provider bias and patient outcomes. Methods: A systematic review of the literature was conducted across five public electronic databases: PubMed, PsycINFO, CINAHL, Web of Science, Embase. Studies included youth/young adults with T1D with a mean age between 12-35 years that investigated the effects of provider bias on physical and psychological health outcomes. Results: Fourteen articles were included in the review. Results suggest experiences of provider bias (e.g., shaming, criticism) negatively affect individuals’ self-esteem, relationships with medical providers, and mood. Provider bias also impacts recommendations about diabetes technology use, insulin regimen intensity, and risk for life-threatening T1D complications. Conclusions: Evidence from the current review suggests that provider bias plays a role in adverse physical and mental health. Varying study methodology in definitions and assessment of provider bias signals a need for comprehensive measure development to account for diverse experiences and interpretations of bias in healthcare. More research is necessary to investigate intervening factors that may affect the association between provider bias and overall health outcomes in youth and young adults with T1D. Disclosure S.E.Wetter: None. A.C.Himelhoch: None. K.A.Driscoll: None.

Skeletal Senescence with Aging and Type 2 Diabetes.

Osteoporosis and type 2 diabetes (T2D) are common diseases that often coexist. While both of these diseases are associated with poor bone quality and increased fracture risk, their pathogenesis of increased fracture risk differs and is multifactorial. Mounting evidence now indicates that key fundamental mechanisms that are central to both aging and energy metabolism exist. Importantly, these mechanisms represent potentially modifiable therapeutic targets for interventions that could prevent or alleviate multiple complications of osteoporosis and T2D, including poor bone quality. One such mechanism that has gained increasing momentum is senescence, which is a cell fate that contributes to multiple chronic diseases. Accumulating evidence has established that numerous boneresident cell types become susceptible to cellular senescence with old age. Recent work also demonstrates that T2D causes the premature accumulation of senescent osteocytes during young adulthood, at least in mice, although it remains to be seen which other bone-resident cell types become senescent with T2D. Given that therapeutically removing senescent cells can alleviate age-related bone loss and T2D-induced metabolic dysfunction, it will be important in future studies to rigorously test whether interventions that eliminate senescent cells can also alleviate skeletal dysfunction in context of T2D, as it does with aging.

Atrophy of the optic chiasm is associated with microvascular diabetic complications in type 1 diabetes.

Diabetic neuropathy and diabetic eye disease are well known complications of type 1 diabetes. We hypothesized that chronic hyperglycemia also damages the optic tract, which can be measured using routine magnetic resonance imaging. Our aim was to compare morphological differences in the optic tract between individuals with type 1 diabetes and healthy control subjects. Associations between optic tract atrophy and metabolic measures, cerebrovascular and microvascular diabetic complications were further studied among individuals with type 1 diabetes. We included 188 subjects with type 1 diabetes and 30 healthy controls, all recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent a clinical examination, biochemical work-up, and brain magnetic resonance imaging (MRI). Two different raters manually measured the optic tract. The coronal area of the optic chiasm was smaller among those with type 1 diabetes compared to non-diabetic controls (median area 24.7 [21.0-28.5] vs 30.0 [26.7-33.3] mm2, p<0.001). In participants with type 1 diabetes, a smaller chiasmatic area was associated with duration of diabetes, glycated hemoglobin, and body mass index. Diabetic eye disease, kidney disease, neuropathy and the presence of cerebral microbleeds (CMBs) in brain MRI were associated with smaller chiasmatic size (p<0.05 for all). Individuals with type 1 diabetes had smaller optic chiasms than healthy controls, suggesting that diabetic neurodegenerative changes extend to the optic nerve tract. This hypothesis was further supported by the association of smaller chiasm with chronic hyperglycemia, duration of diabetes, diabetic microvascular complications, as well as and CMBs in individuals with type 1 diabetes.

Benefits and harms of fibrate therapy in patients with type 2 diabetes: a systematic review and meta-analysis.

This systematic review aimed to evaluate the benefits and harms of fibrate therapy, alone or in combination with statins, in adult patients with type 2 diabetes (T2D). A comprehensive search was conducted in six databases, from inception to January 27, 2022. Clinical trials that compared fibrate therapy with other lipid-lowering interventions or placebo were included. Outcomes of interest comprised cardiovascular (CV) events, complications of T2D, metabolic profile, and adverse events. Random-effects meta-analyses were performed to estimate mean differences (MD) and risk ratios (RR), alongside 95% confidence intervals (CI). A total of 25 studies were included, six comparing fibrates against statins, 11 against placebo, and eight evaluating the combination of fibrates with statins. Overall risk of bias was rated as moderate, and most outcomes rendered low confidence per GRADE approach. Fibrates showed reduction of serum triglycerides (TGs) (MD -17.81, CI -33.92 to -1.69) and a marginal increase of high-density lipoprotein cholesterol (HDL-c) (MD: 1.60, CI 0.29 to 2.90) in adults with T2D, but no differences were found in CV events when compared to statin therapy (RR 0.99, CI 0.76 to 1.09). When used in combination with statins, no major differences were exhibited regarding lipid profile and CV outcomes. Adverse events were comparable between fibrate and statin monotherapies (e.g., RR of 1.03 for rhabdomyolysis, and 0.90 for gastrointestinal events). Fibrate therapy in patients with T2D results in a marginal improvement of TGs and HDL-c but without reducing the risk of CV events and mortality. Their use should be reserved for very specific scenarios after a deliberative dialogue between patients and clinicians regarding their benefits and harms.

Expanded feature space-based gradient boosting ensemble learning for risk prediction of type 2 diabetes complications

As a metabolic disease, diabetes is a serious threat to human health, in which type 2 diabetes (T2D) constitutes about 90% of diabetic cases. As the disease progresses, T2D often comes with various complications such as kidney disease and retinopathy, which may cause huge threats to patients’ health. In recent years, complication prediction of T2D has gained wide research interest as early disease detection and management can effectively reduce the risk of death. In this paper, to break through the limitation of the available data and achieve higher overall prediction accuracy, an improved feature space-based gradient boosting regression tree ensemble (IFS-GBRTE) approach is proposed for the risk prediction of developing T2D complications. Specifically, the original feature space is expanded based on existing feature generation theories. Then the new feature space is refined by comparing the total contribution of each feature during the construction of a classification and regression tree (CART) under a cross-validation scheme. Finally, a gradient boosting ensemble algorithm using CART as base learners is utilized for model training. The prediction model is validated on the T2D data provided by the China National Clinical Medical Science Data Center. The experimental results show that the proposed IFS-GBRTE achieves 82.49% accuracy and realizes better generalization ability than compared single models and ensemble learning models, meanwhile it is helpful to obtain more effective predictive variables for improving the accuracy of risk prediction of T2D complications, which is of great significance for achieving the early prevention, screening and nursing of complications, and further reducing mortality and save medical resources.

Human complement component C3 N-glycome changes in type 1 diabetes complications.

Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity.

Glucose-Lowering Effects of Imeglimin and Its Possible Beneficial Effects on Diabetic Complications.

Mitochondrial dysfunction is a prominent pathological feature of type 2 diabetes, which contributes to β-cell mass reduction and insulin resistance. Imeglimin is a novel oral hypoglycemic agent with a unique mechanism of action targeting mitochondrial bioenergetics. Imeglimin reduces reactive oxygen species production, improves mitochondrial function and integrity, and also improves the structure and function of endoplasmic reticulum (ER), changes which enhance glucose-stimulated insulin secretion and inhibit the apoptosis of β-cells, leading to β-cell mass preservation. Further, imeglimin inhibits hepatic glucose production and ameliorates insulin sensitivity. Clinical trials into the effects of imeglimin monotherapy and combination therapy exhibited an excellent hypoglycemic efficacy and safety profile in type 2 diabetic patients. Mitochondrial impairment is closely associated with endothelial dysfunction, which is a very early event in atherosclerosis. Imeglimin improved endothelial dysfunction in patients with type 2 diabetes via both glycemic control-dependent and -independent mechanisms. In experimental animals, imeglimin improved cardiac and kidney function via an improvement in mitochondrial and ER function or/and an improvement in endothelial function. Furthermore, imeglimin reduced ischemia-induced brain damage. In addition to glucose-lowering effects, imeglimin can be a useful therapeutic option for diabetic complications in type 2 diabetic patients.

Beta Cell Dysfunction in Youth- and Adult-Onset Type 2 Diabetes: An Extensive Narrative Review with a Special Focus on the Role of Nutrients.

Traditionally a disease of adults, type 2 diabetes (T2D) has been increasingly diagnosed in youth, particularly among adolescents and young adults of minority ethnic groups. Especially, during the recent COVID-19 pandemic, obesity and prediabetes have surged not only in minority ethnic groups but also in the general population, further raising T2D risk. Regarding its pathogenesis, a gradually increasing insulin resistance due to central adiposity combined with a progressively defective β-cell function are the main culprits. Especially in youth-onset T2D, a rapid β-cell activity decline has been observed, leading to higher treatment failure rates, and early complications. In addition, it is well established that both the quantity and quality of food ingested by individuals play a key role in T2D pathogenesis. A chronic imbalance between caloric intake and expenditure together with impaired micronutrient intake can lead to obesity and insulin resistance on one hand, and β-cell failure and defective insulin production on the other. This review summarizes our evolving understanding of the pathophysiological mechanisms involved in defective insulin secretion by the pancreatic islets in youth- and adult-onset T2D and, further, of the role various micronutrients play in these pathomechanisms. This knowledge is essential if we are to curtail the serious long-term complications of T2D both in pediatric and adult populations.

Comprehensive Study of Untargeted Metabolomics and 16S rRNA Reveals the Mechanism of Fecal Microbiota Transplantation in Improving a Mouse Model of T2D.

Fecal microbiota transplantation (FMT) has emerged as a new therapy targeting gastrointestinal microbiota for the treatment of a growing number of diseases in recent years. Previous studies have suggested that FMT may be a potential therapy for type 2 diabetes (T2D), but the underlying mechanism remains unclear. Therefore, in the present study, we aimed to investigate the role of FMT in T2D and its underlying mechanisms. To induce T2D, mice were fed a high-fat diet and injected with low-dose streptozotocin (STZ) for four weeks. The mice were then randomly divided into four groups: control group (n = 7), T2D group (n = 7), metformin (MET)-treated group (n = 7), and FMT group (n = 7). The MET group was orally administered 0.2 g/kg MET, the FMT group was orally administered 0.3 mL of bacterial solution, and the other two groups were orally administered the same volume of saline for four weeks. Serum and fecal samples were collected for non-targeted metabolomics, biochemical indicators, and 16S rRNA sequencing, respectively. Our results demonstrated that FMT had a curative effect on T2D by ameliorating hyperlipidemia and hyperglycemia. Using 16S rRNA sequencing and serum untargeted metabolomic analysis, we found that FMT could restore the disorders of gastrointestinal microbiota in T2D mice. Moreover, corticosterone, progesterone, L-urobilin, and other molecules were identified as biomarkers after FMT treatment. Our bioinformatics analysis suggested that steroid hormone biosynthesis, arginine, proline metabolism, and unsaturated fatty acid biosynthesis could be potential regulatory mechanisms of FMT. In summary, our study provides comprehensive evidence for the role of FMT in the treatment of T2D. FMT has the potential to become a promising strategy for the treatment of metabolic disorders, T2D, and diabetes-related complications.

Defecatory disorders in patients with type 1 diabetes and chronic constipation.

Chronic constipation (CC) may be caused by defecatory disorders (DDs) and associated with reduced rectal sensation. Among patients with type 1 diabetes (T1D) and CC (T1DCC patients), the prevalence of DDs and reduced rectal sensation is unknown. We sought to compare complications of T1D, anorectal dysfunction, and CC symptoms, among T1DCC patients with versus without a DD. Anorectal pressures at rest and during squeeze and evacuation, as well as rectal sensation and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry in 114 consecutive T1DCC patients. Thirty-seven patients (32%) had prolonged BET, suggestive of a DD. Complications of T1D included peripheral neuropathy (n = 67, 59%), retinopathy (n = 42, 37%), and nephropathy (n = 26, 23%). Among these complications, only retinopathy was associated with, that is, more prevalent in patients with normal (45%) than prolonged BET (19%). Compared with patients with normal BET, patients with prolonged BET had a lower rectal pressure (mean [SD], 32 [23] mm Hg vs. 23 [19] mm Hg, p = 0.03), greater anal pressure (91 [23] mm Hg vs. 68 [36] mm Hg, p < 0.001), and lower rectoanal gradient (-67 [30] mm Hg vs. -36 [32] mm Hg, p < 0.0001) during evacuation. Anal resting pressure and anal squeeze increment were below normal in 14 (13%) and 32 (29%) of patients and one or more rectal sensory thresholds were above normal in 34 (30%) patients; these abnormalities affected similar proportions in the normal and prolonged BET cohorts. Among T1DCC patients, 37 (32%) had prolonged BET, which was associated with anorectal pressures indicative of a DD but was not associated with reduced rectal sensation, suggesting that DDs are more likely explained by abdomino-anal dyscoordination than visceral disturbance.

Corchorus olitorius extract exhibit anti-hyperglycemic and anti-inflammatory properties in rodent models of obesity and diabetes mellitus.

Obesity and type 2 diabetes (T2D) are chronic conditions with detrimental impacts on the overall health of individuals. Presently, the use of pharmacological agents in obesity and T2D offers limited benefits and pose side effects. This warrant studies on remedies that are less toxic and inexpensive while effective in ameliorating secondary complications in obesity and T2D. Plant-based remedies have been explored increasingly due to their remarkable properties and safety profile. We searched for pre-clinical evidence published from inception until 2023 on PubMed, Scopus, Google, and Semantic scholar on Corchorus olitorius (C. olitorius) in both obesity and T2D. Our focus was to understand the beneficial impact of this plant-based remedy on basic glycemic, lipid, inflammatory, and biomarkers of oxidative stress. The evidence gathered in this review suggests that C. olitorius treatment may significantly reduce blood glucose, body weight, total cholesterol, triglycerides, and low-density lipoprotein (LDL) in concomitant with increasing high-density lipoprotein-cholesterol (HDL-c) in rodent models of obesity and T2D. Interestingly, this effect was consistent with the reduction of malonaldehyde, superoxide dismutase and catalases, tumor necrosis factor-alpha, interleukins, and leptin. Some of the mechanisms by which C. olitorius reduces blood glucose levels is through stimulation of insulin secretion, increasing β-cell proliferation, thus promoting insulin sensitivity; the process which is mediated by ascorbic acid present in this plant. C. olitorius anti-hyperlipidemia is attributable to the content of ferulic acid found in this plant, which inhibits 3-Hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors and thus results in reduced synthesis of cholesterol and increased hepatic LDL-c receptor expression, respectively. The present review provides extensive knowledge and further highlights the potential benefits of C. olitorius on basic metabolic parameters, lipid profile, inflammation, and oxidative stress in rodent models of obesity and T2D.

Risk of Diabetic Complications in Type 2 Diabetes Patients with Dementia: A Population-Based Study Using National Health Insurance Claims Data

Risk of Diabetic Complications in Type 2 Diabetes Patients with Dementia: A Population-Based Study Using National Health Insurance Claims Data