Type 2 Diabetes Group Research Articles

Algorithmic identification of atypical diabetes in electronic health record (EHR) systems.

Understanding atypical forms of diabetes (AD) may advance precision medicine, but methods to identify such patients are needed. We propose an electronic health record (EHR)-based algorithmic approach to identify patients who may have AD, specifically those with insulin-sufficient, non-metabolic diabetes, in order to improve feasibility of identifying these patients through detailed chart review. Patients with likely T2D were selected using a validated machine-learning (ML) algorithm applied to EHR data. "Typical" T2D cases were removed by excluding individuals with obesity, evidence of dyslipidemia, antibody-positive diabetes, or cystic fibrosis. To filter out likely type 1 diabetes (T1D) cases, we applied six additional "branch algorithms," relying on various clinical characteristics, which resulted in six overlapping cohorts. Diabetes type was classified by manual chart review as atypical, not atypical, or indeterminate due to missing information. Of 114,975 biobank participants, the algorithms collectively identified 119 (0.1%) potential AD cases, of which 16 (0.014%) were confirmed after expert review. The branch algorithm that excluded T1D based on outpatient insulin use had the highest percentage yield of AD (13 of 27; 48.2% yield). Together, the 16 AD cases had significantly lower BMI and higher HDL than either unselected T1D or T2D cases identified by ML algorithms (P<0.05). Compared to the ML T1D group, the AD group had a significantly higher T2D polygenic score (P<0.01) and lower hemoglobin A1c (P<0.01). Our EHR-based algorithms followed by manual chart review identified collectively 16 individuals with AD, representing 0.22% of biobank enrollees with T2D. With a maximum yield of 48% cases after manual chart review, our algorithms have the potential to drastically improve efficiency of AD identification. Recognizing patients with AD may inform on the heterogeneity of T2D and facilitate enrollment in studies like the Rare and Atypical Diabetes Network (RADIANT).

Cardiovascular Property of Resistance Training With an Emphasis on PI3K/AKT1 Genes Expression in Type 2 Diabetic Rats

Background: The potential role of exercise in physiological cardiac hypertrophy is rooted in both hormonal and genetic components. Objectives: The aim of this study was to determine the impact of resistance exercise on the expression of PI3K and AKT1 in cardiac tissue of type 2 diabetes (T2D) rats and their physiological cardiac hypertrophy. Methods: First, 21 male Wistar rats (220±20 g) were obese with 6-week high-fat diet (HFD) and were randomly assigned into non-diabetes, control T2D, and exercise diabetes groups. After inducing obesity, T2D was induced by intraperitoneal injection of streptozotocin (25 mg/kg) for diabetes groups. Rats in the exercise group completed a 6-week resistance exercise program, 5 sessions per week. PI3K/AKT1 expression and the weight ratio of left ventricular to heart, heart to body, and left ventricular to body were compared by analysis of variance (ANOVA) between groups. Results: In response to the induction of diabetes, the expression of PI3K/AKT1 in heart tissue decreased significantly compared to that of non-diabetic rats (P=0.001 and P=0.001, respectively). Further, resistance training led to a significant increase in PI3K expression (P=0.028) and AKT1 (P=0.032) and the weight ratio of left ventricular to heart (P=0.001), heart to the body (P=0.001), and left ventricular to the body (P=0.001) compared to control diabetic rats. Conclusion: Resistance training is associated with physiological cardiac hypertrophy in diabetic rats, and this improvement may be attributed to the PI3K/AKT1 signaling pathway.

Multiomics signatures of type 1 diabetes with and without albuminuria.

To identify novel pathophysiological signatures of longstanding type 1 diabetes (T1D) with and without albuminuria we investigated the gut microbiome and blood metabolome in individuals with T1D and healthy controls (HC). We also mapped the functional underpinnings of the microbiome in relation to its metabolic role. One hundred and sixty-one individuals with T1D and 50 HC were recruited at the Steno Diabetes Center Copenhagen, Denmark. T1D cases were stratified based on levels of albuminuria into normoalbuminuria, moderate and severely increased albuminuria. Shotgun sequencing of bacterial and viral microbiome in stool samples and circulating metabolites and lipids profiling using mass spectroscopy in plasma of all participants were performed. Functional mapping of microbiome into Gut Metabolic Modules (GMMs) was done using EggNog and KEGG databases. Multiomics integration was performed using MOFA tool. Measures of the gut bacterial beta diversity differed significantly between T1D and HC, either with moderately or severely increased albuminuria. Taxonomic analyses of the bacterial microbiota identified 51 species that differed in absolute abundance between T1D and HC (17 higher, 34 lower). Stratified on levels of albuminuria, 10 species were differentially abundant for the moderately increased albuminuria group, 63 for the severely increased albuminuria group while 25 were common and differentially abundant both for moderately and severely increased albuminuria groups, when compared to HC. Functional characterization of the bacteriome identified 23 differentially enriched GMMs between T1D and HC, mostly involved in sugar and amino acid metabolism. No differences in relation to albuminuria stratification was observed. Twenty-five phages were differentially abundant between T1D and HC groups. Six of these varied with albuminuria status. Plasma metabolomics indicated differences in the steroidogenesis and sugar metabolism and circulating sphingolipids in T1D individuals. We identified association between sphingolipid levels and Bacteroides sp. abundances. MOFA revealed reduced interactions between gut microbiome and plasma metabolome profiles albeit polar metabolite, lipids and bacteriome compositions contributed to the variance in albuminuria levels among T1D individuals. Individuals with T1D and progressive kidney disease stratified on levels of albuminuria show distinct signatures in their gut microbiome and blood metabolome.

Cardiovascular events and mortality in chronic kidney disease in primary care patients with previous type 2 diabetes and/or hypertension. A population-based epidemiological study (KIDNEES)

BackgroundChronic Kidney Disease (CKD), Type 2 Diabetes (T2D) and Hypertension (HTN) are frequently associated with adverse outcomes. We aimed to estimate the impact of a prior diagnosis of T2D and/or HTN on clinical characteristics, cardiovascular events (CVE) and all-cause mortality (ACM) of patients with CKD.MethodsWe conducted a retrospective cohort study based on primary care electronic health records of people without atherosclerotic cardiovascular disease, aged 18–90 years with incident CKD between January 1, 2007, and December 31, 2017. The association between CKD groups classified according to prior diagnosis of T2D and/or HTN and risk of ACM and CVE at follow-up was evaluated with Cox and Fine-Gray regression models, respectively.Results398,477 patients were included. Median age was 74 years and 55.2% were women. Individuals were classified as CKD with HTN (51.9%), CKD with T2D (3.87%), CKD with HTN/T2D (31.4%) and CKD without HTN/T2D (12.9%). In the multivariate analysis, with the CKD without HTN/T2D group as reference, the ACM Hazard Ratio (HR) was 0.74 (95%CI 0.72–0.75) for the CKD with HTN group, 0.81 (95%CI 0.79–0.83) for CKD with HTN/T2D and 1.14 (95%CI 1.10–1.19) for the CKD with T2D group. The sub distribution HRs for CVE were 1.40 (95%CI 1.34–1.47), 1.70 (95%CI 1.61–1.80) and 1.37 (95%CI 1.26–1.48), respectively.ConclusionIn patients with CKD, the risk of ACM and CVE differed in patients with previous HTN and/or T2D. These comorbidities can help identify individuals at higher risk of adverse outcomes and improve the management of patients with CKD in primary care.

Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RA) and bariatric surgery have proven to be effective treatments for obesity and cardiometabolic conditions. We aimed to explore the early metabolomic changes in response to GLP-1RA (liraglutide) therapy vs. placebo and in comparison to bariatric surgery. MethodsThree clinical studies were conducted: a bariatric surgery cohort study of participants with morbid obesity who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) studied over four and twelve weeks, and two randomized placebo-controlled, crossover double blind studies of liraglutide vs. placebo administration in participants with type 2 diabetes (T2D) and participants with obesity studied for three and five weeks, respectively. Nuclear magnetic resonance spectroscopy-derived metabolomic data were assessed in all eligible participants who completed all the scheduled in-clinic visits. The primary outcome of the study was to explore the changes of the metabolome among participants with obesity with and without T2D receiving the GLP-1RA liraglutide vs. placebo and participants with obesity undergoing bariatric surgery during the three to five-week study period. In addition, we assessed the bariatric surgery effects longitudinally over the twelve weeks of the study and the differences between the bariatric surgery subgroups on the metabolome. The trials are registered with ClinicalTrials.gov, numbers NCT03851874, NCT01562678 and NCT02944500. ResultsBariatric surgery had a more pronounced effect on weight and body mass index reduction (−14.19 ± 5.27 kg and − 5.19 ± 5.27, respectively, p < 0.001 for both) and resulted in more pronounced metabolomic and lipidomic changes compared to liraglutide therapy at four weeks postoperatively. Significant changes were observed in lipoprotein parameters, inflammatory markers, ketone bodies, citrate, and branched-chain amino acids after the first three to five weeks of intervention. After adjusting for the amount of weight loss, a significant difference among the study groups remained only for acetoacetate, β-hydroxybutyrate, and citrate (p < 0.05 after FDR correction). Glucose levels were significantly reduced in all intervention groups but mainly in the T2D group receiving GLP-1RA treatment. After adjusting for weight loss, only glucose levels remained significant (p = 0.001 after FDR correction), mainly due to the glucose change in the T2D group receiving GLP-1RA. Similar results with those observed at four weeks were observed in the surgical group when delta changes at twelve weeks were assessed. Comparing the two types of bariatric surgery, an intervention effect was more pronounced in the RYGB subgroup regarding total triglycerides, triglyceride-rich lipoprotein size, and trimethylamine-N-oxide (p for intervention: 0.031, 0.028, 0.036, respectively). However, after applying FDR correction, these changes deemed to be only suggestive; only time effects remained significant with no significant changes persisting in relation to the types of bariatric surgery. ConclusionsThe results of this study suggest that the early metabolomic, lipid and lipoprotein changes observed between liraglutide treatment and bariatric surgery are similar and result largely from the changes in patients' body weight. Specific changes observed in the short-term post-surgical period between bariatric vs. nonsurgical treated participants, i.e., acetoacetate, β-hydroxybutyrate, and citrate changes, may reflect changes in patient diets and calorie intake indicating potential calorie and diet-driven metabolomics/lipidomic effects in the short-term postoperatively. Significant differences observed between SG and RYGB need to be confirmed and extended by future studies.

Ophthalmic artery changes in type 2 diabetes with and without acute coronary syndrome

BackgroundOcular blood flow provides a new perspective for studying the effects of diabetes and ischemic heart disease on systemic blood flow, pathological mechanisms, and prognosis. Previous studies have analyzed the hemodynamic changes of the ophthalmic artery (OA) in patients with diabetes and ischemic heart disease, but the results remain controversial due to limited observation methods. We aimed to explore the morphological and hemodynamic features in the OA in patients with type 2 diabetes (T2D) with and without acute coronary syndrome (ACS).MethodsIn total, 134 participants, including 30 control participants, 34 with ACS only, 34 with T2D only, and 36 with both ACS and T2D, undergoing computed tomography angiography were enrolled. Three-dimensional OA models were reconstructed, and morphological parameters of the OA were measured. In addition, numerical simulations using computational fluid dynamics were used to acquire hemodynamic parameters of the OA.ResultsIn this study, 134 OA models were reconstructed. Morphological measurements revealed a smaller initial OA diameter in the T2D group than in the other two ACS groups. A hemodynamic simulation showed a significantly lower OA blood velocity in patients with ACS and T2D than that in controls (P < 0.001). The mass flow ratios in all disease groups were lower than those in the control group (P < 0.001, P = 0.020, and P < 0.001, respectively). The ACS and T2D groups had higher OA pressure levels than those of the control group (P = 0.013). The OA blood velocity and mass flow ratio were correlated with several clinical parameters.ConclusionsThis study revealed morphological and hemodynamic differences in the OA between patients with T2D with and without ACS. Furthermore, the hemodynamic characteristics of the OA correlated with clinical prognostic biomarkers, suggesting the potential predictive ability of the OA.

Analysis of myocardial revascularization and endpoints after a 1-year follow-up of patients with acute and chronic coronary artery disease, depending on diabetes presence

Aim. To analyze myocardial revascularization in patients with acute and chronic coronary artery disease (CAD) and with different glycemic status, as well as to evaluate complications after a 1-year follow-up.Material and methods. This prospective comparative clinical study included 202 patients of both sexes with acute and chronic coronary artery disease. Depending on the glycemic status and CAD type, the patients were divided into four groups: acute CAD and type 2 diabetes (T2D); acute CAD without T2D (control group); chronic CAD and T2D; chronic CAD without DM2 (control group). Depending on the clinical condition and the results of coronary angiography, patients underwent various types of myocardial revascularization: balloon angioplasty without stenting, stenting, coronary artery bypass grafting, stenting + coronary artery bypass grafting. One year after discharge, all patients were contacted to evaluate complications and endpoints, which included recurrent myocardial infarction, cerebrovascular accident, readmission, revascularization, and death. Total indicator of endpoints was assessed.Results. Up to 80% of patients with acute and chronic CAD, regardless of glycemic status, underwent revascularization, mainly stenting. The prevalence of stenting among persons without T2D with acute and chronic CAD was significantly higher compared with patients with T2D. The absolute number of patients with coronary artery bypass grafting, including in combination with stenting, was higher in the T2D groups. In groups without T2D, the number of patients with one stent was 2-2,5 times higher compared to groups with T2D — acute CAD (p=0,041) and chronic CAD (p=0,017). The prevalence of implantation of ≥2 stents did not differ between the groups. Within 1 year after discharge, there were more hospitalizations and reoperations among people with acute and chronic CAD and T2D. The groups did not differ in the number of non-fatal and fatal complications, although the absolute numbers of these indicators were higher in patients with T2D. The total number of endpoints in T2D people, regardless of the CAD type, were 2 times higher compared to the corresponding control groups (p&lt;0,001).Conclusion. Most patients with acute and chronic CAD, regardless of glycemic status, underwent myocardial revascularization. In patients without T2D, stenting prevailed, most often of one coronary artery. Patients with T2D, along with stenting, underwent coronary bypass grafting, as well as a combination of these two procedures. After a year of follow-up, the number of complications in patients with T2D was 2 times higher compared to patients without type 2 diabetes, which emphasizes the importance of secondary prevention, including complex drug treatment.

Early choroidal changes detected by swept-source OCT in type 2 diabetes and their association with diabetic kidney disease

IntroductionMicrovascular changes in eye and kidney shares some common factors in diabetes mellitus (DM). The purpose was to evaluate choroidal thickness (CT) and choriocapillaris (CC) density in patients with type...

LBODP042 Lean Type Two Diabetes: Risk Factors And Outcomes Compared To Typical Presenting Type Two Diabetes

Abstract Background Lean type 2 diabetes (LT2D) is a prevalent manifestation of type 2 diabetes (T2D). However, it has been an understudied subgroup of T2D. Aim To compare characteristics and outcomes of patients with LT2D with that of typical presenting T2D. Methods A retrospective review of electronic health records was performed between 2013 and 2020. The study included 254 patients with LT2D and 429 patients with typical T2D located in the South Bay of Southern California. LT2D and typical T2D were defined as having a body mass index (BMI) of 18.5 to 24.9 kg/m2 and 25 to 29.9 kg/m2, respectively. Patient-level variables included age, sex, race, ethnicity, educational level, area of deprivation index (ADI), microvascular and macrovascular comorbidities, alcohol use, tobacco use, and diabetes family history. Labs and vital signs obtained included hemoglobin A1c (HbA1c), glomerular filtration rate (GFR), creatinine, albumin, and blood pressure. Student's t-test and Chi-square tests/Fisher's exact tests were performed with SAS version 9.4 to compare differences between the LT2D and typical T2D groups. Results Between the diabetes subgroups, there were several statistically significant differences identified. The LT2D population was older, with a mean age of 78.2 years compared with 74.6 years in the typical T2D (p &amp;lt; 0. 001). The LT2D group had a higher percentage of Asians at 40.6% and fewer Caucasians at 35. 0%, while the typical T2D consisted of 22.4% Asians and 46.4% Caucasians (p=0. 0007). Diastolic blood pressure was lower in the LT2D group at 71.6 compared to 73.9 in the typical T2D group (p=0. 0053). There were no differences in sex, HbA1c, systolic blood pressure, hypertension, dyslipidemia, chronic kidney disease, cardiovascular events, peripheral vascular disease, combined microvascular complications, combined macrovascular complications, substance use, education level, ADI, GFR, creatinine, albumin, or number of relatives with diabetes. Conclusion We identified several key differences between the LT2D and typical T2D cohort, including age, race, and diastolic blood pressure. Further investigation and large studies are warranted to explore the risk factors and long term outcomes of patients presenting with LT2D. Knowing what the key differences are may help identify appropriate diabetes medical treatments and lifestyle interventions for this particular target population rather than using T2D treatments that are used for a more general population of patients. Presentation: No date and time listed

Associations between urea nitrogen and risk of depression among subjects with and without type 2 diabetes: A nationwide population-based study.

Depression and type 2 diabetes (T2D) are serious public health problems with irreversible health consequences and a significant economic burden on the healthcare system. Previous studies have suggested that blood urea nitrogen (BUN) was inversely longitudinally associated with incidence of diabetes and depression in adults, but few well-designed studies have examined the effects of status of T2D on the full range of relationship between BUN and depression. The analysis sample consisted of adults aged≥20 years from the 2007-2014 National Health and Nutrition Examination Survey (NHANES) who completed the Patient Health Questionnaire-9 (PHQ-9), involving 19,005 participants. By stratifying participants according to T2D status, we further assessed the difference between BUN and risk of depression in participants with and without T2D using multivariate logistic regression (interaction test). In this cross-sectional study, the association between BUN and depression prevalence appeared to differ between the T2D and non-T2D groups (OR: 1.00, 95% Cl: 0.95-1.05 vs. OR: 0.89, 95% Cl: 0.85-0.93). In addition, there was evidence of an interaction between BUN levels and T2D status in reducing the risk of depression (P value for interaction = 0.032.) The relationship between BUN and depressive symptoms was significant in non-T2D subjects (P < 0.001), but not in T2D (P = 0.940). Our findings suggest that there is a significant relationship between BUN and depression, and T2D status may influence the association between BUN and the risk of depression. Such findings require further prospective studies to provide more evidence.

Distinguishing the lipid profile of GCK-MODY patients and its correlation with hsCRP levels.

Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants. The serum lipid profiles of the GCK-MODY group (n=50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n=19), the type 1 diabetes (T1D) group (n=50), and the type 2 diabetes (T2D) group (n=54). The associations between the lipid compositions and the hsCRP levels in each group were also explored. Elevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5±0.27) compared with the T1D (1.2±0.47, p<0.01) and T2D (1.3±0.3, p<0.01) groups. On the other hand, a significantly lower LDL-C level (2.4±0.69) in the GCK-MODY group compared with the T1D (2.7±0.72, p<0.01) and T2D (2.9±0.68, p<0.01) groups was also noted. A lower ratio of triglyceride to HDL-C (TG/HDL) and a lower hsCRP level were also found in the GCK-MODY group [TG/HDL=0.38 (0.25-0.52), hsCRP=0.2mg/L (0.16-0.37)] compared with the T1D group [(TG/HDL=0.56 (0.39-1.29), hsCRP=0.56mg/L (0.39-1.29), p<0.01] and the T2D group [(TG/HDL=1.6 (1.1-2.68), hsCRP=1.11mg/L (0.66-2.34), p<0.01]. Although patients with HNF1A-MODY showed similar hsCRP levels [0.17 (0.08-0.52), p>0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66-1.76), p<0.05] and TG/HDL ratios [0.84 (0.56-1.31), p<0.05]. Analysis of the correlations between the hsCRP levels and lipid profiles of each group confirmed that the LnhsCRP (natural logarithm-transformed hsCRP level) was positively correlated with the LnTG (natural logarithm-transformed TG) (r=0.352, p=0.011) and the Ln(TG/HDL) ratio (r=0.283, p=0.047) only in individuals with GCK-MODY. Individuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.

The Accelerated Progression of Atherosclerosis Correlates with Decreased miR-33a and miR-21 and Increased miR-122 and miR-3064-5p in Circulation and the Liver of ApoE-/- Mice with Streptozocin (STZ)-Induced Type 2 Diabetes.

Atherosclerosis is a major risk factor for type 2 diabetes (T2D) mortality. We aim to investigate the changes in miR-21, miR-122, miR-33a and miR-3064-5p in circulation and the liver of ApoE-/- mice with streptozocin (STZ)-induced T2D. Twenty 5-week-old male ApoE-/- mice were randomly assigned to the control (n = 10) and T2D group (n = 10) and intraperitoneally injected with a citrate buffer and streptozotocin (STZ) (40 mg/kg BW) once a day for three consecutive days. The successfully STZ-induced T2D mice (n = 5) and control mice (n = 5) were then fed with a high-fat diet (HFD) for 34 weeks. Compared to the control mice, ApoE-/- mice with STZ-induced T2D had slower (p < 0.05) growth, increased (p < 0.05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), decreased (p < 0.05) high-density lipoprotein cholesterol (HDL-C) in serum, reduced (p < 0.05) TC and sterol regulatory element-binding protein-2 (Srebp-2), elevated (p < 0.05) ATP-binding-cassette-transporter-A1 (Abca1) in the liver, aggravated (p < 0.05) atherosclerotic lesions in the aorta, downregulated (p < 0.05) miR-21 and miR-33a, and upregulated (p < 0.05) miR-122 and miR-3064-5p in serum and the liver. In addition, the aortic lesions showed a positive correlation with miR-122 (r = 1.000, p = 0.001) and a negative correlation with miR-21 (r = −1.000, p = 0.001) in ApoE-/- mice with T2D. In conclusion, T2D-accelerated atherosclerosis correlates with a reduction in miR-21 and miR-33a and an elevation in miR-122 and miR-3064-5p in circulation and the liver of ApoE-/- mice.

Vitamin D levels and Vitamin D-related gene polymorphisms in Chinese children with type 1 diabetes.

Low vitamin D levels may play a role in type 1 diabetes (T1D) susceptibility. Since 25(OH)D synthesis is genetically regulated, single nucleotide polymorphisms (SNPs) of important genes have also been shown to modulate the risk of T1D, so this study aimed to investigate the relationship between five SNPs in CYP2R1, DHCR7, CYP24A1, VDR genes, serum 25(OH)D levels and T1D in Chinese children. This case-control study included 141 T1D patients and 200 age-matched healthy children.25 (OH) D concentration was determined, genotyping was performed by High resolution melting (HRM). There was a significant difference in the prevalence of vitamin D deficiency, insufficiency, and sufficiency between T1D and healthy controls. (χ2 = 10.86, p = 0.004), however no evidence of the association between any group of SNPs and circulating 25(OH) D levels was observed. The allele distribution of CYP2R1(rs1993116) was significantly different between T1D and control group (p = 0.040), and the C allele carriers of rs1993116 had a higher risk of T1D than the T allele carriers, Carriers of the CC and CT genotypes of rs1993116 have higher T1D risk than those carrying the TT genotype. GMDR analysis revealed a significant interaction between CYP2R1(rs12794714) and CYP2R1(rs1993116) in the risk of T1D with a maximum testing balance accuracy of 60.39%.

Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes.

BackgroundIn contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.MethodsA prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.ResultsThere was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.ConclusionsLinagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.

Impact of dysglycemia and obesity on the brain in adolescents with and without type 2 diabetes: A pilot study.

Both diabetes and obesity can affect the brain, yet their impact is not well characterized in children with type 2 (T2) diabetes and obesity. This pilot study aims to explore differences in brain function and cognition in adolescents with T2 diabetes and obesity and nondiabetic controls with obesity and lean controls. Participants were 12-17 years old (5 T2 diabetes with obesity [mean HgbA1C 10.9%], 6 nondiabetic controls with obesity and 10 lean controls). Functional MRI (FMRI) during hyperglycemic/euglycemic clamps was performed in the T2 diabetes group. When children with obesity, with and without diabetes, were grouped (mean BMI 98.8%), cognitive scores were lower than lean controls (BMI 58.4%) on verbal, full scale, and performance IQ, visual-spatial and executive function tests. Lower scores correlated with adiposity and insulin resistance but not HgbA1C. No significant brain activation differences during task based and resting state FMRI were noted between children with obesity (with or without diabetes) and lean controls, but a notable effect size for the visual-spatial working memory task and resting state was observed. In conclusion, our pilot study suggests that obesity, insulin resistance, and dysglycemia may contribute to relatively poorer cognitive function in adolescents with T2 diabetes and obesity. Further studies with larger sample size are needed to assess if cognitive decline in children with obesity, with and without T2 diabetes, can be prevented or reversed.

Association between Pediatric Adenovirus Infection and Type 1 Diabetes.

Background: Viruses are among the inducers of type 1 diabetes (T1D) as they are implicated in the initiation of β-cell destruction. This study aimed to explore the link between adenoviruses’ infection, inflammatory biomarkers, and the development of T1D. Methods: The study population included 80 children with T1D and 40 healthy controls (2–16 years old). The T1D group was further clustered into two groups according to time of T1D diagnosis: a group of children who were diagnosed during the first year of life and a second group who were diagnosed after the first year of life. Adenovirus DNA, anti-adenovirus IgG, cytokines, and lipid profiles were screened in the different groups. The results were statistically assessed using one-way analysis of variance (ANOVA) and LSD t-test. Results: Positive adenovirus PCR was detected in 2.5% and 20% of normal and T1D children, respectively. Moreover, the positive PCR results for adenovirus were found significantly higher in the T1D group, who were diagnosed during the first year of life (33.4%), in comparison to those diagnosed after the first year of life (12%). Anti-adenoviruses IgG was found in 12.5% and 40% of healthy controls and diabetic children, respectively. Seropositive results were found to be higher in newly diagnosed children (46.7%) in comparison to those previously diagnosed with T1D (36%). Body mass index (BMI), IFN-γ, IL-15, adiponectin, lipid profile, and microalbuminuria were significantly increased in T1D adenoviruses-positive children compared to children who were negative for adenoviruses. Conclusions: Adenovirus infection could be among the contributing risk factors and may play a role in the induction of T1D in children.

Evaluation of motor vehicle crashes between scooter riders and car drivers after diagnosis of type 2 diabetes in Taiwan

BackgroundDespite the plausibility that diabetes may increase the risk of motor vehicle crashes (MVCs) due to various diabetes related complications and co-morbidity, findings from epidemiological studies on the relationship between diabetes and MVCs remained inclusive mainly due to heterogeneity in the study design and failure to complete consideration of potential confounders. This study re-visited this putative association with an improved study design. MethodThis study employed a controlled before–after study design and included 1,264,280 people aged 18–75 years with T2D newly diagnosed from 2009–2014 and an equal number of age-, sex-, and time-matched controls. The rate ratios (RRs) of vehicle type–specific incidence rates of MVCs in the 1 and 2 years before and after diabetes diagnosis (or the matched dates) were compared between the individuals with type 2 diabetes (T2D) and their matched controls. ResultsThe rate of MVCs increased slightly among people with T2D over 1 and 2 years following diabetes diagnosis, with RRs of 1.04 (95% confidence interval [CI]=1.02–1.07) and 1.11 (95% CI=1.09–1.13), respectively. These RRs were comparable to those obtained for controls (1.06 and 1.12, respectively). By contrast, the RRs of scooter crashes were significantly higher in the T2D group than in the control group during the 1 year (1.28 vs. 1.08, p < 0.001) and 2 years (1.32 vs. 1.08, p < 0.001) following diabetes diagnosis. Conclusion: T2D diagnosis was associated with a moderate but significant increase in the risk of MVCs among scooter drivers, but not among car drivers.

Type-1 diabetes and pulmonary function tests. A meta-analysis

ObjectivesTo determine the association between type-1 diabetes (T1D) and pulmonary function tests. MethodsAfter conducting an exhaustive literature search, we performed a meta-analysis. We employed the inverse variance method with a random effects model to calculate the effect estimate as the mean difference (MD) and 95% confidence interval (CI). We calculated the heterogeneity with the I2 statistic and performed a meta-regression analysis by age, sex, body mass index (BMI), smoking and geographical region. We also conducted a sensitivity analysis according to the studies’ publication date, size of the T1D group and the study quality, excluding the study with the greatest weight in the effect. ResultsThe meta-analysis included 39 studies, one longitudinal, 35 case-control and three cross-sectional ones, with 1274 patients with T1D and 1353 control participants. The pooled MD (95%CI) for the predicted percentage of FEV1, FVC, FEF25–75%, PEF and DLCO were −6.40 (95%CI -8.55, −4.25; p < 0.001), −6.39 (95%CI -8.46, −4.33; p < 0.001), −6.14 (95%CI -10.73, −1.56; p = 0.009), −9.32 (95%CI -14.15, −4.50; p = 0.0002) and −0.64 (95%CI -1.12, −0.16; p = 0.008), respectively. There was no difference in the ratio of FEV1/FVC (−0.33 95%CI -1.70, 1.03; p = 0.28). There was considerable heterogeneity. The meta-regression analysis showed that between studies heterogeneity was not explained by patient age, sex, BMI, smoking or geographical region. The findings were consistent in the sensitivity analysis. ConclusionsT1D is associated with impaired pulmonary function, independently of age, sex, smoking, BMI, and geographical region. Longitudinal studies are needed to investigate outcomes for patients with T1D and impaired pulmonary function.

DISTRIBUTION OF KCNJ11 RS5219 POLYMORPHISM IN VIETNAMESE POPULATION AND ITS ASSOCIATION WITH HYPERGLYCEMIA

Aims: KCNJ11 gene, encoding ATP-sensitive channel subunits, involves in insulin secretion. The study aimed at investigating the distribution of the KCNJ11 E23K (rs5219) polymorphism and its association with prediabetes and type 2 diabetes (T2D) in Vietnamese population. Methods: A cross-sectional study randomly recruited 2.676 participants aged 40-64 years from a general population in Ha Nam province, Vietnam. Glycemic status of the subjects was classified based on fasting plasma glucose and oral glucose tolerance test. PCR-restriction fragment length polymorphism method was applied to detect the KCNJ11-rs5219 polymorphism. Genotype frequencies were compared to find the distribution difference among normoglycemic, prediabetes, and T2D groups. Generalized linear models and multinomial logistic regression analysis were used to determine the associations of the KCNJ11-rs5219 polymorphism with prediabetes and T2D. Results: The frequencies of minor K allele in normoglycemic, prediabetes and T2D groups were 33.2, 32.6 and 35.4%, respectively. Genotype distribution of the E23K polymorphism was in Hardy-Weinberg equilibrium and not significantly different among the three glucose groups (p &gt; 0.05). Fasting plasma glucose and 2-h glucose levels were not significantly different among three genotypes EE, EK, and KK (p &gt; 0.05). After adjusted for social-economic status, lifestyle and clinical patterns, no significant association was found between the KCNJ11-rs5219 polymorphism and hyperglycemia with ORs from 0.80 to 1.29. Conclusions: The minor K allele was predominant and genotype frequency in the population was remained constant among generations. The study suggests no significant association between the KCNJ11-rs5219 polymorphism and hyperglycemia in the Vietnamese population.

The Bright Side of Skin Autofluorescence Determination in Children and Adolescents with Newly Diagnosed Type 1 Diabetes Mellitus: A Potential Predictor of Remission?

Skin autofluorescence (SAF) is a noninvasive method reflecting tissue accumulation of advanced glycation end products (AGEs). We investigated whether, in newly diagnosed children and adolescents with type 1 diabetes (T1D), this surrogate marker of long-term glycemia is associated with markers of the early manifestation phase, residual secretion capacity of the ß-cells, and the occurrence of remission. SAF was measured in 114 children and adolescents (age: 8.0 ± 4.5 years, 44% girls) at the time of T1D diagnosis, and related to HbA1c, C-peptide, diabetic ketoacidosis, and remission. 56 patients were followed up for 1 year. Seventy-four sex- and age-matched healthy individuals served as controls. SAF was higher in the T1D group compared with controls (1.0 ± 0.2 vs. 0.9 ± 0.2, p < 0.001). At the time of diagnosis, SAF correlated with HbA1c (r = 0.285, p = 0.002), was similar in patients with and without ketoacidosis, and was lower in the remitters compared with non-remitters (0.95 ± 0.18 vs. 1.04 ± 0.26, p = 0.027). Unlike HbA1c, SAF was an independent predictor of remission (∆R2 = 0.051, p = 0.004). Former studies consider SAF in diabetic patients as a tool to identify individuals at an increased risk of chronic complications. Here we show that determination of SAF at the time of T1D diagnosis might potentially predict remission, at least in children.