Future Development Of Diabetes Research Articles

Association of C-reactive protein with future development of diabetes: a population-based 7-year cohort study among Norwegian adults aged 30 and older in the Tromsø Study 2007–2016

ObjectivesThe extent to which observed associations between high-sensitivity C-reactive protein (hs-CRP) and incident diabetes are explained by obesity and hypertension remains unclear. This study aimed to investigate the association of...

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD)

ObjectiveWe aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population.SettingPopulation-based retrospective cohort study using annual health check-up data...

Association between periodontal pocket depth determined during dental check-ups and new onset of diabetes in community residents: the LIFE study

Objectives Recent studies have shown a bidirectional association between diabetes and periodontal disease. However, the longitudinal association between periodontal pocket depth and new onset of diabetes remains controversial. Therefore, this study aimed to examine the association between periodontal pocket depth and new onset of diabetes using dental check-up data in a community-based population.Methods The study comprised 5,163 participants aged≥20 years (mean age±standard deviation, 57.4±13.9 years; women, 66.3%) who underwent dental check-ups between April 2016 and March 2019 in a Tokyo ward. We classified the participants into three groups using community periodontal index codes from dental check-ups: healthy periodontal pocket group, periodontal pocket 4-5 mm group, and periodontal pocket ≥6 mm group. The participants were followed until the end of March 2020. Additionally, data on individuals who developed diabetes in the same ward were acquired from the National Health Insurance and Latter-Stage Older Persons Health Care System using ICD-10 codes. As the study outcome, we identified individuals who developed diabetes after the dental check-up date. Diabetes incidence rates were compared using the log-rank test and Cox regression analysis. Additionally, we performed a sensitivity analysis using a similar framework.Results The log-rank test showed that the cumulative incidence of diabetes between the three groups was significantly different (P<0.01). A Cox regression analysis model adjusted for sex, age, smoking habits, number of teeth present, and oral hygiene status showed that the diabetes development hazard ratio (HR) for the periodontal pocket ≥6 mm group was 1.44 (95% confidence interval [CI]; 1.04-2.00) when compared with that of the healthy periodontal pocket group. In the sensitivity analysis of individuals aged ≥40 years, the HR for the periodontal pocket ≥6 mm group was 1.55 (95% CI; 1.11-2.16) when compared with that of the healthy periodontal pocket group. Similarly, among men aged ≥40 years, the HR for the periodontal pocket ≥6 mm group was 1.72 (95% CI; 1.04-2.85) when compared with that of the healthy periodontal pocket group. However, no significant association between new onset of diabetes and periodontal pocket depth was found for women aged ≥40 years (HR=1.39, 95% CI; 0.89-2.18).Conclusion This The study suggests a longitudinal association between periodontal pocket depth and new onset of diabetes. The association was particularly pronounced in men aged ≥40 years. Therefore, men aged <40 years should maintain good oral health through appropriate dental health guidance to prevent the future development of diabetes.

Significant impact of body mass index on the relationship between increased white blood cell count and new-onset diabetes.

An elevated white blood cell (WBC) count has been linked to incident diabetes. WBC count has been positively associated with body mass index (BMI), and elevated BMI has been reported to be a strong predictor of future diabetes. Hence, the association of increased WBC count with the subsequent development of diabetes may be mediated by increased BMI. This study was designed to address this issue. We selected subjects from the 104,451 participants enrolled from 2012 to 2018 in the Taiwan Biobank. We only included those with complete data at baseline and follow-up and those without diabetes at baseline. Finally, 24,514 participants were enrolled in this study. During an average 3.88 years of follow-up, 248 (1.0%) of the participants had new-onset diabetes. After adjusting for demographic, clinical, and biochemical parameters, increased WBC count was associated with new-onset diabetes in all of these participants (p ≤ 0.024). After further adjustment for BMI, the association became insignificant (p = 0.096). In addition, subgroup analysis of 23,430 subjects with a normal WBC count (range: 3500-10500/µl) demonstrated that increased WBC count was significantly associated with new-onset diabetes after adjusting for demographic, clinical, and biochemical parameters (p ≤ 0.016). After further adjustment for BMI, this association was attenuated (p = 0.050). In conclusion, our results showed that BMI had a significant impact on the relationship between increased WBC count and new-onset diabetes in all study participants, and BMI also attenuated the association in those with a normal WBC count. Hence, the association between increased WBC count and the future development of diabetes may be mediated by BMI.

High pulse pressure is associated with an increased risk of diabetes in females but not in males: a retrospective cohort study

ObjectiveAccumulating evidence suggests a close relationship between metabolic disturbance and increased arterial stiffness. However, whether there is an association between pulse pressure (PP) and diabetes and how this association might be impacted by sex is not clear.MethodsA total of 209,635 adult Chinese individuals > 20 years old across 32 sites and 11 cities in China (Shanghai, Beijing, Nanjing, Suzhou, Shenzhen, Changzhou, Chengdu, Guangzhou, Hefei, Wuhan, Nantong) were included in the study; participants were free of diabetes at baseline. In the present study, we analyzed the relationship between PP at baseline and incident diabetes using the Cox proportional hazard model.ResultsDuring a median follow-up of 2.99 years, a total of 3971 participants (2885 men and 1086 women) developed diabetes, and the incidence was 6.3 per 1000 person-years. With each 10 mmHg increase in PP, the multivariable adjusted hazard ratio (HR) (95% confidence interval) for incident diabetes was 1.117 (1.061, 1.176) in females and 0.981 (0.951, 1.012) in males. Using the lowest quartile of PP as the reference category, the hazard ratio (HR) (95% CI) of the highest quartile of PP for incident diabetes was 1.494 (1.225, 1.822) in females and 0.939 (0.843, 1.045) in males. Smooth plots revealed a significant difference between males and females in the HRs for new-onset diabetes according to PP.ConclusionHigher PP was related to future diabetes development in females but not in males and further research is needed to explore the mechanism.

Prameha purvaroopa as diabetes risk predictor - trends from a retrospective cohort study of newly diagnosed type 2 diabetes patients

Study backgroundIncreasing prevalence of type 2 diabetes has shifted the focus of world from its management to prevention. Life style modifications programs related to diabetes prevention are found to delay the progress of prediabetes into diabetes. Reaching out to community with diabetes prevention program however is still a challenge to meet. ObjectiveOf the study: This study proposed to retrospectively screen the presence of prediabetes symptoms depicted in Ayurveda literature in a newly diagnosed diabetic population and to compare this prevalence with non-diabetic and healthy population. The idea is to put weightage upon prediabetes symptoms as a disease predictor if these are available early in the course of the disease. Material and methodsA questionnaire based upon detailed literature survey of three Ayurveda classics from the subject area of prameha (identical to diabetes) identified 22 features under the class of prediabetes. A questionnaire was developed to find the presence of these features in selected diabetic population retrospectively before the onset of diabetes. 141 newly diagnosed diabetics were selected on the basis of a defined inclusion and exclusion criteria and surveyed for chronological presence of prediabetes features as identified through the literature search and validated through a validation process. This feature prevalence was further compared with non-diabetic and healthy population. ResultsA significant difference (p < 0.001) was observed in specific symptom occurrence in diabetic population comparing to non-diabetic and healthy control for at least 11 of the selected items. ConclusionThe study observes that few prediabetes features show their clear retrospective presence in diabetic population comparing to non-diabetic and healthy population. This observation can help formulating a risk calculator for future diabetes on the basis of available pre diabetic features in an individual. A prospective cohort study however would be essential to prove any such realistic relation between prediabetes symptoms and future diabetes development among high risk individuals.

Cholecystectomy is associated with dysglycaemia: Cross‐sectional and prospective analyses

Cholecystectomy has been reported to be associated with increased risk of diabetes in cross‐sectional studies. In the current study, we performed both cross‐sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community‐dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow‐up visit were calculated to define glycaemic control as stable (−10% ≤ Δ < 10%), improved (Δ < −10%), or worsened (Δ ≥ 10%). The baseline cross‐sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) (P < 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that individuals in the Chinese community‐dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group.

An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data.

The early prediction and identification of risk factors for diabetes may prevent or delay diabetes progression. In this study, we developed an interactive online application that provides the predictive probabilities of prediabetes and diabetes in 4 years based on a Bayesian network (BN) classifier, which is an interpretable machine learning technique. The BN was trained using a dataset from the Ansung cohort of the Korean Genome and Epidemiological Study (KoGES) in 2008, with a follow-up in 2012. The dataset contained not only traditional risk factors (current diabetes status, sex, age, etc.) for future diabetes, but it also contained serum biomarkers, which quantified the individual level of exposure to environment-polluting chemicals (EPC). Based on accuracy and the area under the curve (AUC), a tree-augmented BN with 11 variables derived from feature selection was used as our prediction model. The online application that implemented our BN prediction system provided a tool that performs customized diabetes prediction and allows users to simulate the effects of controlling risk factors for the future development of diabetes. The prediction results of our method demonstrated that the EPC biomarkers had interactive effects on diabetes progression and that the use of the EPC biomarkers contributed to a substantial improvement in prediction performance.

Long-term effects of the changes in hepatic steatosis status on the risk of incident type 2 diabetes mellitus: A 15-year community-based prospective cohort study

AimsWe investigated the long-term effect of changes in hepatic steatosis on the risk of developing T2DM. MethodsWe evaluated 3510 participants from the 2001–2016 Korean Genome and Epidemiology Study. Those with significant alcohol consumption or T2DM during 2001–2004 were excluded. Steatosis was defined as non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS) of over −0.64, and baseline values were assessed between 2001 and 2002. Differences in NAFLD-LFS (ΔLFS) and changes in steatosis status (no, intermittent [resolved or incident], and persistent steatosis) were assessed between 2003 and 2004. Changes in the risk of diabetes status were observed until 2016. ResultsOver 52,650 person-years of follow-up, T2DM developed in 296 participants (8.4%). The incidence of diabetes in those with no steatosis, intermittent steatosis, and persistent steatosis during follow-up increased by 5.1%, 14.1%, and 27.1% respectively. Multivariate-adjusted analysis revealed that the risk was higher in those with persistent steatosis than those with no steatosis and intermittent steatosis. Baseline NAFLD-LFS and ΔLFS was associated with increased risk of incident T2DM. ConclusionsInitial severity as well as aggravation of steatosis is an independent predictor of incident T2DM. Strategies aimed at reducing liver fat may prevent future development of diabetes among patients with NAFLD.

Metabolic Syndrome and Its Components Are Associated With Altered Amino Acid Profile in Chinese Han Population.

ObjectiveRecent studies have found that the levels of plasma amino acids, such as branched-chain amino acids and aromatic amino acids, were associated with visceral obesity, insulin resistance, future development of diabetes and cardiovascular diseases. However, few studies have involved a Chinese Han population. This study aimed to examine the association between amino acid profile and metabolic syndrome (MetS) and its components in the Chinese Han population.MethodsThis is a cross-sectional study, which enrolled a cohort of 473 participants from a community. We employed the isotope internal standard method to determine the plasma concentrations of 28 amino acids using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). Participants were divided into MetS (n = 72) and non-MetS groups (n = 401) to analyze the association between amino acids and MetS and its components.ResultsThe prevalence of MetS was 15.2% according to the criteria. Plasma concentrations of isoleucine (Ile), leucine (Leu), valine (Val), tyrosine (Tyr), tryptophan (Trp), phenylalanine (Phe), glutamic acid (Glu), aspartic acid (Asp), alanine (Ala), histidine (His), methionine (Met), asparagine (Asn), and proline (Pro) were significantly higher in the MetS group than those in the non-MetS group (P < 0.05), but taurine (Tau) was significantly lower (P < 0.05). When MetS components were increased, the concentrations of these 13 amino acids significantly increased (P < 0.05), but Tau concentration was significantly decreased (P < 0.05). We extracted the amino acid profile by principal component analysis (PCA), PC1 and PC2, which extracted from the 14 amino acids, were significantly associated with MetS (odds ratio, 95% confidence interval: 1.723, 1.325–2.085 and 1.325, 1.043–1.684, respectively). A total of 260 non-MetS participants were followed up effectively, and 42 participants developed new-onset MetS within 5 years. We found that the amino acid profile of PC1 was linked to the occurrence of future MetS. Decreased Tau was correlated with the future development of MetS.ConclusionParticipants with MetS exhibit an abnormal amino acid profile, and its components gradually increase when these amino acids are altered. Amino acid PCA profile can be employed for assessing and monitoring MetS risk. Finally, decreased Tau may be linked to the future development of MetS.

Not Only Diabetes but Also Prediabetes Leads to Functional Decline and Disability in Older Adults.

OBJECTIVEDiabetes is linked to functional decline, but the impact of prediabetes on physical function is unknown. We aimed to examine and compare the impact of prediabetes and diabetes on physical function and disability progression and to explore whether cardiovascular diseases (CVDs) mediate these associations.RESEARCH DESIGN AND METHODSA cohort of 2,013 participants aged ≥60 from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing population-based longitudinal study, was monitored for up to 12 years. Physical function was measured with chair stand (s) and walking speed (m/s) tests, and disability was measured by summing the numbers of impaired basic and instrumental activities of daily living. Diabetes was identified through medical examinations or clinical records, medication use, or glycated hemoglobin (HbA1c) ≥6.5%. Prediabetes was defined as HbA1c ≥5.7–6.4% in participants free of diabetes. CVDs were ascertained through clinical examinations and the National Patient Register. Data were analyzed using mixed-effect models and mediation models.RESULTSAt baseline, 650 (32.3%) had prediabetes and 151 had diabetes (7.5%). In multiadjusted mixed-effect models, prediabetes was associated with an increased chair stand time (β 0.33, 95% CI 0.05–0.61), a decreased walking speed (β −0.006, 95% CI −0.010 to −0.002), and an accelerated disability progression (β 0.05, 95% CI 0.01–0.08), even after controlling for the future development of diabetes. Diabetes led to faster functional decline than prediabetes. In mediation analyses, CVDs mediated 7.1%, 7.8%, and 20.9% of the associations between prediabetes and chair stand, walking speed, and disability progression, respectively.CONCLUSIONSPrediabetes, in addition to diabetes, is associated with faster functional decline and disability, independent of the future development of diabetes. This association may be in part mediated by CVDs.

Prediabetes among HIV-infected individuals receiving antiretroviral therapy: prevalence, diagnostic tests, and associated factors

BackgroundMetabolic complications in human immunodeficiency virus (HIV)-infected individuals are common. Prediabetes represents a high risk for future diabetes development. This study aimed to determine the prevalence, diagnostic methods, and associated factors of prediabetes among HIV-infected individuals receiving antiretroviral therapy (ART).MethodsA cross-sectional study was conducted among HIV-infected adults without a history of diabetes who were receiving ART. Fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) after a 75-g oral glucose tolerance test, and hemoglobin A1c (HbA1c) were assessed.ResultsA total of 397 patients with a mean age of 47.0 ± 9.8 years and 55.7% male, were studied. All received ART with undetectable plasma viral load. The mean duration of ART was 9.6 ± 5.2 years, and the mean CD4 cell count was 554 ± 235 cells/mm3. Among the patients, 28 (7.1%) had first-diagnosed diabetes, and 133 (33.5%) patients had prediabetes. Glycemia estimation by FPG, 2-h PG, and HbA1c showed a prediabetes prevalence of 17.4%, 14.7%, and 12.5%, respectively. The kappa statistics for the agreement of FPG and 2-h PG, HbA1c and 2-h PG, and HbA1c and FPG were 0.317, 0.429, and 0.396, respectively. In multivariate analysis, hypertension [odds ratio (OR) 3.38; 95% confidence interval (CI), 1.16-9.91; p = 0.026), and triglycerides > 150 mg/dL (OR 2.11; 95% CI, 1.01-4.44; p = 0.047) were factors significantly associated with prediabetes.ConclusionsPrediabetes among HIV-infected individuals receiving ART is common. The agreements of glycemia estimation methods are minimal to weak. HbA1c may underestimate prediabetes prevalence. Using FPG together with HbA1c increases the detection rate to approximately three-quarters of prediabetes patients. HIV-infected individuals who had hypertension and hypertriglyceridemia should be regularly assessed for prediabetes.Trial registration ClinicalTrial.gov, NCT03545217. Registered 1 June 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03545217

Serum biomarkers from cell-based assays for AhRL and MIS strongly predicted the future development of diabetes in a large community-based prospective study in Korea

Exposure to environment-polluting chemicals (EPC) is associated with the development of diabetes. Many EPCs exert toxic effects via aryl hydrocarbon receptor (AhR) and/or mitochondrial inhibition. Here we investigated if the levels of human exposure to a mixture of EPC and/or mitochondrial inhibitors could predict the development of diabetes in a prospective study, the Korean Genome and Epidemiological Study (KoGES). We analysed AhR ligands (AhRL) and mitochondria-inhibiting substances (MIS) in serum samples (n = 1,537), collected during the 2008 Ansung KoGES survey with a 4-year-follow-up. Serum AhRL, determined by the AhR-dependent luciferase reporter assay, represents the contamination level of AhR ligand mixture in serum. Serum levels of MIS, analysed indirectly by MIS-ATP or MIS-ROS, are the serum MIS-induced mitochondria inhibiting effects on ATP content or reactive oxygen species (ROS) production in the cultured cells. Among 919 normal subjects at baseline, 7.1% developed impaired glucose tolerance (IGT) and 1.6% diabetes after 4 years. At the baseline, diabetic and IGT sera displayed higher AhRL and MIS than normal sera, which correlated with indices of insulin resistance. When the subjects were classified according to ROC cut-off values, fully adjusted relative risks of diabetes development within 4 years were 7.60 (95% CI, 4.23–13.64), 4.27 (95% CI, 2.38–7.64), and 21.11 (95% CI, 8.46–52.67) for AhRL ≥ 2.70 pM, MIS-ATP ≤ 88.1%, and both, respectively. Gender analysis revealed that male subjects with AhRL ≥ 2.70 pM or MIS-ATP ≤ 88.1% showed higher risk than female subjects. High serum levels of AhRL and/or MIS strongly predict the future development of diabetes, suggesting that the accumulation of AhR ligands and/or mitochondrial inhibitors in body may play an important role in the pathogenesis of diabetes.

Advanced Techniques for Predicting the Future Progression of Type 2 Diabetes

Diabetes is a costly and burdensome metabolic disorder that occurs due to the elevation of glucose levels in the bloodstream. If it goes unchecked for an extended period, it can lead to the damage of different body organs and develop life-threatening health complications. Studies show that the progression of diabetes can be stopped or delayed, provided a person follows a healthy lifestyle and takes proper medication. Prevention of diabetes or the delayed onset of diabetes is crucial, and it can be achieved if there exists a screening process that identifies individuals who are at risk of developing diabetes in the future. Although machine learning techniques have been applied for disease diagnosis, there is little work done on long term prediction of disease, type 2 diabetes in particular. Moreover, finding discriminative features or risk-factors responsible for the future development of diabetes plays a significant role. In this study, we propose two novel feature extraction approaches for finding the best risk-factors, followed by applying a machine learning pipeline for the long term prediction of type 2 diabetes. The proposed methods have been evaluated using data from a longitudinal clinical study, known as the San Antonio Heart Study. Our proposed model managed to achieve 95.94% accuracy in predicting whether a person will develop type 2 diabetes within the next 7–8 years or not.

Abdominal fat depots, insulin resistance, and incident diabetes mellitus in women with and without HIV infection.

The aim of this study was to determine the associations between visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) mass with homeostatic model assessment-insulin resistance (HOMA-IR) and incidence of diabetes mellitus in women with and without HIV infection. Cross-sectional design for associations between abdominal fat and HOMA-IR; longitudinal design for associations between abdominal fat and incident diabetes. We assessed associations between dual X-ray absorptiometry scan-derived VAT and SAT with HOMA-IR in a subsample from the Women's Interagency HIV Study (n = 226 with and n = 100 without HIV) using linear regression. We evaluated associations of VAT, SAT and HOMA-IR with incident diabetes mellitus using Cox proportional hazards models. VAT mass was positively associated with log HOMA-IR in fully adjusted linear regression models stratified by HIV serostatus, including adjustment for SAT. During median follow-up of 10.6 years, incidence of diabetes was 1.63 [95% confidence interval (95% CI) 1.15-2.31] and 1.32 [95% CI 0.77-2.28] cases per 100 person-years in women with and without HIV (P = 0.52). In a fully adjusted model, baseline VAT (hazard ratio 2.64 per kg; 95% CI 1.14-6.12; P = 0.023) and SAT (hazard ratio 1.34 per kg; 95% CI 0.73-2.45; P = 0.35) were associated with incident diabetes, but the latter was not statistically significant. VAT mass was independently associated with HOMA-IR in women with and without HIV and was independently associated with future development of diabetes.

Identifying Prediabetes and Type 2 Diabetes in Asymptomatic Youth: Should HbA1c Be Used as a Diagnostic Approach?

Because the incidence of type 2 diabetes and prediabetes in children is rising, routine screening of those at risk is recommended. In 2010, the ADA made the recommendation to include hemoglobin A1c (HbA1c) as a diagnostic test for diabetes, in addition to the oral glucose tolerance test or fasting plasma glucose. Our objective was to assess the pediatric literature with regard to HbA1c test performance and discuss advantages and disadvantages of use of the test for diagnostic purposes. HbA1c has a number of advantages, including elimination of the need for fasting, lower variability, assay standardization, and long-term association with future development of diabetes. It also has many drawbacks. It can be affected by a number of non-glycemic factors, including red blood cell turnover, hemoglobinopathies, medications, race, and age. In particular, it performs differently in children compared with adults, generally with lower sensitivity for prediabetes (as low as 0-5% in children vs 23-27% in adults) and lower area under the receiver operating characteristic curve (AUC) (0.53 vs 0.73 for prediabetes), and it has lower efficacy at a higher cost, compared with other tests of glycemia. Finally, HbA1c may perform very differently across diverse populations according to race/ethnicity; in Chinese populations, the proportion of individuals classified with prediabetes based on HbA1c predominates compared with IFG (77% for HbA1c vs 27.7% for IFG), whereas in US populations, it is the opposite (24.8% for HbA1c vs 80.1% for FPG). HbA1c is controversial because although it is convenient, it is not a true measure of glycemia. The interpretation of HbA1c results requires a nuanced understanding that many primary care physicians who are ordering the test in greater numbers do not possess. Alternative markers of glycemia may hold promise for the future but are not yet endorsed for use in practice. Further studies are needed to determine appropriate thresholds for screening tests and the long-term impact of screening and identification.

Cardio-metabolic risk and its management in a cohort of clozapine-treated outpatients

ObjectiveTo comprehensively assess cardio-metabolic risk factors and their management in a large sample of outpatients treated with clozapine. MethodsObservational cross-sectional study of all clozapine users attending specialized clozapine monitoring outpatient clinics in three public hospitals in Sydney, Australia were approached to participate over the one-year period 01/10/2015–30/09/2016. Cardio-metabolic risk factors including metabolic syndrome, risk for future development of diabetes, smoking, physical activity, nutrition, and prescribed medications were assessed at face-to-face interview and through medical record review. Among patients who had cardio-metabolic risk factors, the proportion receiving appropriate management was assessed. ResultsOf 451 registered clozapine clinic attenders, 92.2% completed questionnaires and anthropometric measurements. 58.3% met criteria for metabolic syndrome. 79.6% were overweight or obese. 55.9% had blood pressure meeting metabolic syndrome criteria. 46.6% had elevated fasting blood glucose and 55.2% had elevated blood triglycerides. 43.6% were current smokers. Only 10% achieved recommended weekly physical activity levels. Unhealthy food categories were highly consumed. 32.1% were on additional antipsychotics. In the majority of individuals, cardio-metabolic risk factors were untreated or under-treated. ConclusionsClozapine use was associated with very high rates of cardiovascular and metabolic risk factors, which were frequently under-treated. Management of both physical and mental health should be prioritized. Polypharmacy should be rationalized. Future research should investigate the effectiveness of smoking cessation and lifestyle interventions in this high-risk population.

The postpartum effect of maternal diabetes on the circulating levels of sirtuins and superoxide dismutase.

Gestational diabetes mellitus (GDM) is a glucose intolerance disorder which occurs during pregnancy as a result of insulin insensitivity; it usually disappears after delivery. However, some women with GDM can develop type 2 diabetes (T2D) after delivery, and the mechanisms by which this occurs remain unknown. This study compared the levels of sirtuins (NAD‐dependent deacetylases) and antioxidative enzymes in postpartum women with previous GDM (pGDM) or T2D and in postpartum women with a previous healthy pregnancy (controls). Women with pGDM showed upregulated levels of sirtuin 1 (SIRT1) mRNA and protein, with reduced expression levels of sirtuin 3 (SIRT3) and superoxide dismutase 2 (SOD2), relative to the controls. Women with T2D similarly showed a lower level of SIRT3 mRNA than the controls. Lipid peroxidation (malondialdehyde) was higher in women with pGDM than in the controls. These data show that in women with pGDM, the reduced level of SIRT3 may play a role in the reduced SOD2 level, possibly leading to oxidative stress, which, in turn, upregulates the level of SIRT1. These results might confer the risk of future diabetes development in women with pGDM, as a similar reduction in SIRT3 was found in women with T2D.

Microalbuminuria as a simple predictor of incident diabetes over 8 years in the Korean Genome and Epidemiology Study (KoGES)

Microalbuminuria (MAU) is a common subclinical disease and related with cardiovascular outcome both in diabetic and non-diabetic patients. However, there is rare data about the effect of MAU on the development of diabetes. Thus, we aimed to investigate whether MAU is associated with the development of incident diabetes. A total of 3385 subjects without diabetes (1503 men and 1882 women; mean age, 53 years) who participated in the Ansung–Ansan cohort study from 2001–2002 (baseline) to 2011–2012 (fifth follow-up visit) were followed for a mean of 8 years. The prevalence of MAU at baseline was 10.8% (365 patients), and the incidence of newly developed diabetes during the follow-up period was 15.3% (56 patients) in subjects with MAU. The hazard ratio (HR) for development of diabetes was 1.43 (95% confidence interval (CI) 1.07–1.91, p-value 0.016), independent of traditional risk factors for diabetes including pre-diabetes, age, obesity, and family history. The impact of MAU on diabetes was also significant in the non-pre-diabetic population (HR 2.08, 95% CI 1.07–4.03, p-value 0.031). In conclusion, our results show that incident MAU is associated with future development of diabetes and could be an early marker for diabetes, even in the non-prediabetic population.

Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes.

MicroRNAs (miRNAs) are key regulators of gene expression and novel biomarkers for many diseases. We investigated the hypothesis that serum levels of some miRNAs would be associated with islet autoimmunity and/or progression to type 1 diabetes. We measured levels of 93 miRNAs most commonly detected in serum. This retrospective cohort study included 150 autoantibody-positive and 150 autoantibody-negative family-matched siblings enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort (mean age=11years), and most autoantibody-positive relatives were at high risk because they had multiple autoantibodies, with 39/150 (26%, progressors) developing type 1 diabetes within an average 8.7months of follow-up. We analysed miRNA levels in relation to autoantibody status, future development of diabetes and OGTT C-peptide and glucose indices of disease progression. Fifteen miRNAs were differentially expressed when comparing autoantibody-positive/negative siblings (range -2.5 to 1.3-fold). But receiver operating characteristic (ROC) analysis indicated low specificity and sensitivity. Seven additional miRNAs were differentially expressed among autoantibody-positive relatives according to disease progression; ROC returned significant AUC values and identified miRNA cut-off levels associated with an increased risk of disease in both cross-sectional and survival analyses. Levels of several miRNAs showed significant correlations (r values range 0.22-0.55) with OGTT outcomes. miR-21-3p, miR-29a-3p and miR-424-5p had the most robust associations. Serum levels of selected miRNAs are associated with disease progression and confer additional risk of the development of type 1 diabetes in young autoantibody-positive relatives. Further studies, including longitudinal assessments, are warranted to further define miRNA biomarkers for prediction of disease risk and progression.