Early Type 2 Diabetes Mellitus Research Articles

Progress in Cardiac Magnetic Resonance Feature Tracking for Evaluating Myocardial Strain in Type-2 Diabetes Mellitus.

The global prevalence of type-2 diabetes mellitus (T2DM) has caused harm to human health and economies. Cardiovascular disease is one main cause of T2DM mortality. Increased prevalence of diabetes and associated heart failure (HF) is common in older populations, so accurately evaluating heart-related injury and T2DM risk factors and conducting early intervention are important. Quantitative cardiovascular system imaging assessments, including functional imaging during cardiovascular disease treatment, are also important. The left-ventricular ejection fraction (LVEF) has been traditionally used to monitor cardiac function; it is often preserved or increased in early T2DM, but subclinical heart deformation and dysfunction can occur. Myocardial strains are sensitive to global and regional heart dysfunction in subclinical T2DM. Cardiac magnetic resonance feature-tracking technology (CMR-FT) can visualize and quantify strain and identify subclinical myocardial injury for early management, especially with preserved LVEF. Meanwhile, CMR-FT can be used to evaluate the multiple cardiac chambers involvement mediated by T2DM and the coexistence of complications. This review discusses CMR-FT principles, clinical applications, and research progress in the evaluation of myocardial strain in T2DM.

PyCaret for Predicting Type 2 Diabetes: A Phenotype- and Gender-Based Approach with the "Nurses' Health Study" and the "Health Professionals' Follow-Up Study" Datasets.

Predicting type 2 diabetes mellitus (T2DM) by using phenotypic data with machine learning (ML) techniques has received significant attention in recent years. PyCaret, a low-code automated ML tool that enables the simultaneous application of 16 different algorithms, was used to predict T2DM by using phenotypic variables from the "Nurses' Health Study" and "Health Professionals' Follow-up Study" datasets. Ridge Classifier, Linear Discriminant Analysis, and Logistic Regression (LR) were the best-performing models for the male-only data subset. For the female-only data subset, LR, Gradient Boosting Classifier, and CatBoost Classifier were the strongest models. The AUC, accuracy, and precision were approximately 0.77, 0.70, and 0.70 for males and 0.79, 0.70, and 0.71 for females, respectively. The feature importance plot showed that family history of diabetes (famdb), never having smoked, and high blood pressure (hbp) were the most influential features in females, while famdb, hbp, and currently being a smoker were the major variables in males. In conclusion, PyCaret was used successfully for the prediction of T2DM by simplifying complex ML tasks. Gender differences are important to consider for T2DM prediction. Despite this comprehensive ML tool, phenotypic variables alone may not be sufficient for early T2DM prediction; genotypic variables could also be used in combination for future studies.

Effect of gout and diabetic kidney disease on renal cancer development in Korea.

Chronic kidney disease (CKD) and gout are risk factors for renal cancer. We analysed the effects of comorbid diabetic kidney disease and gout on renal cancer. This retrospective cohort study enrolled 847884 patients with type 2 diabetes mellitus (T2DM) who underwent health assessments provided by the Korean National Health Insurance Service in 2009. Based on CKD occurrence (glomerular filtration rate <60ml/min/1.73m2) and gout (two outpatient visits or one hospitalization within 5years), patients were classified into four groups: CKD-Gout- (87.5%), CKD-Gout+ (2.5%), CKD+Gout- (9.3%) and CKD+Gout+ (0.7%). Patients with incident renal cancer (International Classification of Diseases code C64) were followed up until December 2018. Renal cancer was diagnosed in 2376 patients (0.3%). Renal cancer incidence increased in sequential order of CKD-Gout- [0.29/1000 person-years (PY), CKD+Gout- and CKD-Gout+ (0.44 and 0.48/1000 PY, respectively) and CKD+Gout+ (1.14/1000 PY). Comorbid gout increased renal cancer risk depending on CKD occurrence {hazard ratio [HR] 1.28 [95% confidence interval (CI) 1.04-1.58 among those without CKD; HR 1.95 [95% CI 1.45-2.63] among those with CKD; P-value for interaction=0.024}. The interaction was significant, particularly in men and patients with a shorter diabetes duration (<5years) and lesser medication use (no insulin or fewer than three classes of oral hypoglycaemic agents). CKD and gout individually contributed to renal cancer incidence, and the risk is further increased when gout coexists with CKD. Screening for gout and appropriate management of CKD at an early T2DM stage may be beneficial.

Preoperative contributing factors and the remission of diabetes after metabolic surgery: the mediating role of preoperative triglyceride

Background and objectiveLimited understanding exists regarding the factors affecting the prognosis of surgical treatment for type 2 diabetes mellitus (T2DM), particularly in Chinese patients. In this study, we examined a cohort of early and intermediate obese T2DM patients to explore the potential impact of preoperative lipid metabolism in metabolic surgery on the postoperative remission of T2DM.MethodsParticipants with T2DM and obesity underwent metabolic surgery. Clinical data, including baseline body mass index, percentage of excess weight loss, and preoperative biochemical indicators, were collected and analyzed. A multidisciplinary team conducted patient follow-up. Remission was defined as sub-diabetic hyperglycemia (HbA1c < 48 mmol/mol, fasting glucose 100–125 mg/dl) without pharmacological intervention for at least 12 months.ResultsOver a median follow-up of 27 months, 96 T2DM patients with metabolic surgery were studied, with no laparotomies required. Among these patients, 61 (63.5%) achieved complete remission, and 85 (88.5%) experienced remission. In multivariable analysis models, preoperative fasting blood glucose (FBG) significantly correlated with all postoperative outcomes. Furthermore, mediation analysis indicated that preoperative triglycerides (TG) mediated 26.31% of the association between preoperative FBG and postoperative remission. Both preoperative FBG and TG were negatively associated with the postoperative remission of T2DM.ConclusionIn summary, our findings suggest that lower preoperative fasting glucose levels enhance the likelihood of postoperative T2DM remission. Moreover, preoperative TG could potentially play a mediating role in the postoperative remission of T2DM. Therefore, evaluating and managing fasting glucose and lipids before the procedure may aid in assessing the prognosis of metabolic surgery.Level of evidence Level III, designed cohort.

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up. Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

Triglycerides and risk of cardiovascular events in statin-treated patients with newly diagnosed type 2 diabetes: a Danish cohort study

BackgroundElevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care.MethodsThis cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005–2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors.ResultsAmong 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0–1.9 mmol/L in 52%, 2.0–2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00–1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12–1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20–1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women.ConclusionsIn statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention.

Micro- and macro-changes in early-stage type 2 diabetes mellitus without cognitive impairment: a diffusion tensor imaging (DTI) and surface-based morphometry (SBM) study.

Brain structure and function changes are considered major brain damages in type 2 diabetes mellitus (T2DM), which likely has a close relationship with cognitive impairment. Many previous studies have shown by using brain structural and functional magnetic resonance imaging (MRI) methods that brain white and gray matter are damaged in T2DM, leading to cognitive impairment. Researches neglected patients of T2DM without cognitive dysfunction might also have brain changes. In this study, subjects with early stage T2DM with no cognitive dysfunction were enrolled to detect brain damages using the tract-based spatial statistics analysis (TBSS) method to demonstrate white matter (WM) micro changes and surface-based morphometry (SBM) method to assess cerebral cortex macro changes. The whole-brain TBSS analysis revealed that there were no statistically significant changes in fractional anisotropy (FA) and mean diffusivity (MD), but the FA declined in some area of cerebral WM (p < 0.1). The SBM results showed no changes in cortical thickness (CT), cortical volume (CV), surface area (SA), and cortical sulcal curve (CSC) between these two groups, but pial local gyration index (LGI) was decreased in the precuneus (-log10, p = -3.327). In conclusion, early stage T2DM patients without cognitive impairment had brain micro and macro structural damages, suggesting the potential use of MRI as an imaging marker to detect brain changes in early stage T2DM, which could not be observed and assessed clinically.

Integrated biomarker profiling of the metabolome associated with type 2 diabetes mellitus among Tibetan in China

IntroductionMetabolomic signatures of type 2 diabetes mellitus (T2DM) in Tibetan Chinese population, a group with high diabetes burden, remain largely unclear. Identifying the serum metabolite profile of Tibetan T2DM (T-T2DM) individuals may provide novel insights into early T2DM diagnosis and intervention.MethodsHence, we conducted untargeted metabolomics analysis of plasma samples from a retrospective cohort study with 100 healthy controls and 100 T-T2DM patients by using liquid chromatography–mass spectrometry.ResultsThe T-T2DM group had significant metabolic alterations that are distinct from known diabetes risk indicators, such as body mass index, fasting plasma glucose, and glycosylated hemoglobin levels. The optimal metabolite panels for predicting T-T2DM were selected using a tenfold cross-validation random forest classification model. Compared with the clinical features, the metabolite prediction model provided a better predictive value. We also analyzed the correlation of metabolites with clinical indices and found 10 metabolites that were independently predictive of T-T2DM.ConclusionBy using the metabolites identified in this study, we may provide stable and accurate biomarkers for early T-T2DM warning and diagnosis. Our study also provides a rich and open-access data resource for optimizing T-T2DM management.

NF-κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia-induced oxidative stress and the release of pro-inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM-induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-κB is implicated in the pathogenesis of T2DM, and activation of NF-κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α-synuclein and degeneration of dopaminergic neurons in the SN. Increasing α-synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)-1β followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF-κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic β-cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF-κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.

Puerperium experience and lifestyle in women with gestational diabetes mellitus and overweight/obesity in China: A qualitative study.

Women with overweight or obesity and gestational diabetes mellitus (GDM) are at a high risk of developing type 2 diabetes mellitus (T2DM) and other metabolic diseases. Healthy postpartum lifestyles in women with GDM are important for effectively preventing early T2DM occurrence; however, few studies and guidelines focus in China on this issue. This qualitative study aimed to understand the puerperium experience and lifestyle of women with overweight/obesity and GDM. A face-to-face, in-depth, and semi-structured interview was conducted using a hermeneutical phenomenology method to collect data that were analyzed through thematic analysis. Out of 61 recruited women with overweight/obesity and history of GDM, 14 women underwent an interview and provided detailed descriptions of their lifestyle experiences during puerperium. The interview data were used to generate four themes-puerperium dietary behavior, weight perception and "confinement" behavior, family support, disease knowledge, and perceived risk-and nine sub-themes. Unhealthy lifestyles, misconceptions about food, the conflict between physical activity and confinement behavior, a lack of social and family support, and low awareness of disease risk are all common among overweight/obese women with a history of GDM. Thus, we emphasized that healthcare providers should provide continuous preventive care from pregnancy to postpartum and promote long-term health in high-risk populations with a history of GDM associated with overweight/obesity.

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes.

Coronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM. New Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis. The stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = -0.562 and 0.886, respectively; p < 0.001). The stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM.

Quantitatively Evaluating the Relationships between Insulin Resistance and Retinal Neurodegeneration with Optical Coherence Tomography in Early Type 2 Diabetes Mellitus

Introduction: The aim of this study was to quantitatively assess retinal neurodegenerative changes with optical coherence tomography (Cirrus HD-OCT) in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR) and evaluate their relationships with insulin resistance (IR) and associated systemic indicators. Methods: 102 T2DM patients without DR and 48 healthy controls were included in this observational cross-sectional study. The OCT parameters of macular retinal thickness (MRT) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were evaluated between diabetic and normal eyes. The receiver operating characteristics (ROC) curve was generated to evaluate the discrimination power of early diabetes. Correlation and multiple regression analysis were performed between ophthalmological parameters and T2DM-related demographic and anthropometric variables, and serum biomarkers and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Results: MRT and GCIPL thicknesses showed significant thinning in patients, especially in inferotemporal area. High body mass index (BMI) correlated with decreased GCIPL thicknesses and elevated intraocular pressure (IOP). A negative correlation between waist-to-hip circumference ratio (WHR) and GCIPL thicknesses was also found. High-density lipoprotein (HDL) and fasting C-peptide (CP0) were associated with GCIPL thickness but only in inferotemporal region (r = 0.20, p = 0.04; r = −0.20, p = 0.05, respectively). Multiple regression analysis showed that increased HOMA-IR scores independently predicted both average (β = −0.30, p = 0.05) and inferotemporal (β = −0.34, p = 0.03) GCIPL thinning. Conclusion: Retinal thinning in early T2DM was associated with obesity-related metabolic disorders. IR as an independent risk factor for retinal neurodegeneration may increase the risk of developing glaucoma.

Gut Microbiota Composition in Prediabetes and Newly Diagnosed Type 2 Diabetes: A Systematic Review of Observational Studies.

Evidence of gut microbiota involvement in regulating glucose metabolism and type 2 diabetes mellitus (T2DM) progression is accumulating. The understanding of microbial dysbiosis and specific alterations of gut microbiota composition that occur during the early stages of glucose intolerance, unperturbed by anti-diabetic medications, is especially essential. Hence, this systematic review was conducted to summarise the existing evidence related to microbiota composition and diversity in individuals with prediabetes (preDM) and individuals newly diagnosed with T2DM (newDM) in comparison to individuals with normal glucose tolerance (nonDM). A systematic search of the PubMed, MEDLINE and CINAHL databases were conducted from inception to February 2021 supplemented with manual searches of the list of references. The primary keywords of “type 2 diabetes”, “prediabetes”, “newly-diagnosed” and “gut microbiota” were used. Observational studies that conducted analysis of the gut microbiota of respondents with preDM and newDM were included. The quality of the studies was assessed using the modified Newcastle-Ottawa scale by independent reviewers. A total of 18 studies (5,489 participants) were included. Low gut microbial diversity was generally observed in preDM and newDM when compared to nonDM. Differences in gut microbiota composition between the disease groups and nonDM were inconsistent across the included studies. Four out of the 18 studies found increased abundance of phylum Firmicutes along with decreased abundance of Bacteroidetes in newDM. At the genus/species levels, decreased abundance of Faecalibacterium prausnitzii, Roseburia, Dialister, Flavonifractor, Alistipes, Haemophilus and Akkermansia muciniphila and increased abundance of Lactobacillus, Streptococcus, Escherichia, Veillonella and Collinsella were observed in the disease groups in at least two studies. Lactobacillus was also found to positively correlate with fasting plasma glucose (FPG), HbA1c and/or homeostatic assessment of insulin resistance (HOMA-IR) in four studies. This renders a need for further investigations on the species/strain-specific role of endogenously present Lactobacillus in glucose regulation mechanism and T2DM disease progression. Differences in dietary intake caused significant variation in specific bacterial abundances. More studies are needed to establish more consistent associations, between clinical biomarkers or dietary intake and specific gut bacterial composition in prediabetes and early T2DM.

The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drugnaive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study.

To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543.

Sex Differences in Insulin Sensitivity and Glomerular Function in African Green Monkeys

In the United States, it is estimated that approximately 10.5% of the population has diabetes of which 90% are classified as insulin resistant expressing Type 2 Diabetes Mellitus (T2DM). T2DM is one of the leading causes of end stage renal disease (ESRD) accounting for approximately 40% of new ESRD cases. Previous studies have reported a more prevalent decrease in renal function in glucose intolerant males when compared to pre‐menopausal females. Males also have been reported to have earlier onset and higher prevalence of T2DM compared to pre‐menopausal females. Renal injury can be present before the onset of T2DM however, sex differences in renal injury have yet to be assessed in humans. A subpopulation of African Green Monkeys (AGM; Chlorocebus aethiops sabaeus) in the Caribbean exhibit spontaneous glucose intolerance and co‐morbidities such as insulin insensitivity, and hypertension. The AGM also shares similar genomic expression and metabolic phenotypes to humans making them optimal for translatable diabetes research. We hypothesize that female AGM are protected against renal injury and early onset T2DM. Systolic blood pressure (SBP) was measured by forearm plethysmography. Glucose tolerance was assessed via conscious and anesthetized oral glucose tolerance tests (OGTT). All AGM were fasted 12‐18 hours prior to study with water provided ad libitum. Blood glucose was measured at 0, 15, 30, 60, 90, and 120 min after an oral glucose load. Conscious AGM OGTT were delivered as 0.75g glucose/kg body weight. Sedated AGM (ketamine, 15mg/kg, i.m.), received 5g/dl glucose and 15 ml/kg in water by oral gavage. Venous blood samples were collected at timepoints 0, 30, 60, and 120 minutes post glucose administration. Urine samples were collected for 3 days post OGTT. Kidney histology was performed by staining 10µm sections with Periodic‐Acid Schiff stain (PAS). A minimum of 10 glomeruli were identified at 400x magnification per animal then analyzed with ImageJ. There were no differences between lightly sedated or conscious OGTT. All AGM in this study were normotensive and there were no sex differences in blood pressure between male and female AGM (F=11; 113.9±3.73 mmHg, M=6; 117.6 ± 6.3mmHg). Female AGM OGTT area under the curve (AUC) over 120 minutes post glucose load were lower compared to male AGM (F; 11,961.5± 710.6 min x mg/dl, M; 14,076.3±710.6 min x mg/dl, p&lt;0.05). There were no significant differences in plasma insulin at all time points between male and female AGM (F; 2,013± 1,007 min x mIU/L, M; 5,940± 1,424.6 min x mIU/L) despite the lower glucose AUC in females. Renal glomerular function was assessed by measuring plasma creatinine, urinary albumin, and urinary albumin to creatinine ratio (UACR). Plasma creatinine was not different between male and females (F; 1.35±0.2 mg/dl, M; 1.77±0.25 mg/dl). Microalbuminuria was present in both male and female AGMs, in the absence of sex differences (F; 98.43±23.1 ng/ml, M; 81.15±29.2 ng/ml). UACRs were not different between male and female AGM. Glomerular injury was assessed by determining the intensity of glomerular PAS stain. PAS stain intensity was not different in male and female AGM (F=3; 178.3 ± 8.6, M=3; 181.6± 8.6) regardless of OGTT sensitivity. Together these data suggest that female AGM are more insulin sensitive than male AGM and may be protected against early onset T2DM. Despite differences in OGTT in male and female AGM, microalbuminuria suggested onset of renal dysfunction. We conclude that the AGM provides a strong nonhuman primate model of T2DM for the long‐term study of sex differences in the mechanisms of ESRD.

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

BackgroundSoluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment.MethodsForty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels.ResultsBaseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment.ConclusionsLiraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement.Trial registration Eudract: 2013-001356-36

Zanechání kouření a riziko diabetes mellitus 2. typu

Risk of type 2 diabetes mellitus (T2DM) is higher in tobacco smokers compared to non-smokers. The risk declines after smoking cessation. However, ex-smokers are also more prone to the metabolic syndrome. The question thus is, whether ex-smokers could temporarily have a higher risk of T2DM than current smokers. The available studies on this topic are not in agreement in their conclusions, as most of them also primarily do not compare ex-smokers to current smokers, but to non-smokers. However, based on the available studies, it rather seems the risk of T2DM is temporarily higher after smoking cessation. The higher risk of T2DM seems to be enhanced by weight gain that typically occurs first years after smoking cessation without intervention. Therefore, smoking cessation in patients who are in an increased risk of T2DM should be accompanied by T2DM preventative measures (lifestyle modification, weight monitoring and recommendation of pharmacotherapy of tobacco addiction to lower the risk of weight gain) and more frequent checks of blood glucose level to ensure early T2DM detection.

The whole-brain voxel-based morphometry study in early stage of T2DM patients.

AimThis study aimed to investigate the alterations in whole‐brain gray matter density in early stage type 2 diabetes mellitus (T2DM) patients with cognitive impairment using magnetic resonance imaging.MethodsThirty‐six cases of early stage T2DM patients with cognitive impairment (T2DM‐CI), 34 cases of early stage T2DM patients without cognitive impairment (T2DM) and 30 cases of healthy controls (HC) were enrolled. Montreal Cognitive Assessment (MoCA) and Mini‐Mental State Examination (MMSE) scores were used to identify the cognitive impairment. The whole‐brain gray matter density was analyzed using 3D‐T1 BRAVO imaging, using the voxel‐based morphometry method on T1 structure imaging of two groups.ResultsThe correlation analysis of total gray matter density with MMSE and MoCA scores in the T2DM‐CI group was performed. There were no significant differences in MMSE and MoCA scores between the HC and T2DM groups. However, the MMSE and MoCA scores in the T2DM‐CI group were significantly reduced compared with the T2DM group. There were no significant differences in age, gender, education, body mass index (BMI) or blood pressure among the three groups. Voxel‐based morphometry (VBM) results showed that the density of left triangle part of inferior frontal gyrus, orbital part of inferior frontal gyrus and opercular part of inferior frontal gyrus and left insula in the T2DM‐CI group decreased compared with the T2DM group. Correlation analysis results showed that there was a significant positive correlation between total gray matter density and scores of MMSE and MoCA scores in the T2DM‐CI group.ConclusionIn conclusion, total gray matter density is positively correlated with the scores of MMSE and MoCA in T2DM patients, which may be an early sign of cognitive impairment in patients with T2DM.

Diabetes Mellitus in Prader-Willi Syndrome: Natural History during the Transition from Childhood to Adulthood in a Cohort of 39 Patients.

Type 2 diabetes mellitus (T2DM) affects 20% of patients with Prader-Willi syndrome (PWS), with many cases diagnosed during the transition period. Our aim was to describe the natural history of T2DM in patients with PWS before the age of 25 years and to develop screening and preventive strategies. Thirty-nine patients followed in the French PWS Reference Center were included (median age 25.6 years [23.7; 31.7]). Twenty-one had been treated with growth hormone (GH), fifteen had not, and three had an unknown status. The median age at T2DM diagnosis was 16.8 years (11–24) and the median BMI was 39 kg/m2 [34.6; 45], with 34/35 patients living with obesity. The patients displayed frequent psychiatric (48.3% hospitalization,) and metabolic (56.4% hypertriglyceridemia,) comorbidities and a parental history of T2DM (35.7%) or overweight (53.6%) compared to the PWS general population. There was no difference in BMI and metabolic complications between the GH-treated and non-GH-treated groups at T2DM diagnosis. Patients with PWS who develop early T2DM have severe obesity, a high frequency of psychiatric and metabolic disorders, and a family history of T2DM and overweight. These results underline the need for early identification of patients at risk, prevention of obesity, and repeated blood glucose monitoring during the transition period.

The "Early Treatment" Approach Reducing Cardiovascular Risk in Patients with Type2 Diabetes: A Consensus From an Expert Panel Using the Delphi Technique.

IntroductionThere is no consensus on the optimal therapeutic approach to adopt in patients with newly diagnosed type 2 diabetes mellitus (T2DM) to prevent cardiovascular disease (CVD). The study aimed to gather an expert consensus on the hypoglycemic treatment and CV risk management in patients with newly diagnosed T2DM through the Delphi methodology.MethodsTo address this issue, a list of 30 statements concerning the definition of “early T2DM patient”, early treatment, CV risk in T2DM, treat-to-benefit approach, and indications for treatment with glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors was developed. Using a two-round Delphi methodology, the survey was distributed to 80 Italian diabetes specialists who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement.ResultsA total of 27/30 statements achieved consensus. A patient was defined as “early” according to pathophysiological or clinical interpretation, and/or the timing of the diagnosis. There was agreement on the importance to reach the lowest possible HbA1c level, since diagnosis, also using combination therapy with hypoglycemic drugs with a proven CV benefit. There was a consensus that a treat-to-benefit approach involves the addition of a glucose-lowering agent with proven CV benefits to metformin since diagnosis. The use of GLP-1RAs and SGLT2 inhibitors was considered a key strategy in this approach and the benefits were recognized also for patients with T2DM without established CVD. GLP-1RAs should be used at an earlier stage than SGLT2 inhibitors to prevent CVD, especially in patients with evidence of subclinical atherosclerotic disease.ConclusionThis Delphi consensus recognized the importance to adopt a tailored hypoglycemic treatment of patients with T2DM according to their CVD risk and the key role of glucose-lowering agents with proven CV efficacy, GLP-1RAs and SGLT2 inhibitors, in the context of an early treat-to-benefit approach.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01045-7.