Normal Glucose Metabolism Research Articles

Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V.

Dysglycemia, in this survey defined as impaired glucose tolerance (IGT) or type 2 diabetes, is common in patients with coronary artery disease (CAD) and associated with an unfavorable prognosis. This European survey investigated dysglycemia screening and risk factor management of patients with CAD in relation to standards of European guidelines for cardiovascular subjects. The European Society of Cardiology's European Observational Research Programme (ESC EORP) European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V (2016-2017) included 8,261 CAD patients, aged 18-80 years, from 27 countries. If the glycemic state was unknown, patients underwent an oral glucose tolerance test (OGTT) and measurement of glycated hemoglobin A1c. Lifestyle, risk factors, and pharmacological management were investigated. A total of 2,452 patients (29.7%) had known diabetes. OGTT was performed in 4,440 patients with unknown glycemic state, of whom 41.1% were dysglycemic. Without the OGTT, 30% of patients with type 2 diabetes and 70% of those with IGT would not have been detected. The presence of dysglycemia almost doubled from that self-reported to the true proportion after screening. Only approximately one-third of all coronary patients had completely normal glucose metabolism. Of patients with known diabetes, 31% had been advised to attend a diabetes clinic, and only 24% attended. Only 58% of dysglycemic patients were prescribed all cardioprotective drugs, and use of sodium-glucose cotransporter 2 inhibitors (3%) or glucagon-like peptide 1 receptor agonists (1%) was small. Urgent action is required for both screening and management of patients with CAD and dysglycemia, in the expectation of a substantial reduction in risk of further cardiovascular events and in complications of diabetes, as well as longer life expectancy.

Sequential delayed [18\u2009F]FDG PET/CT examinations in the pharynx

This study aimed to evaluate the usefulness of the biphasic 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography/computed tomography ([18 F]FDG PET/CT) examinations in terms of distinguishing benign and malignant lesions within the pharynx. 139 patients underwent sequential biphasic [18 F]FDG PET/CT examinations at 60 and 90 minutes (min) post intravenous injection (p.i.) of the [18 F]FDG. We evaluated the metabolic activity of 93 malignant lesions and 59 benign findings within pharynx as well as 70 normal blood vessels. We evaluated the maximal and mean standardized uptake value (SUVmax, SUVmean) and the retention index (RI-SUVmax). We used the receiver operating characteristics (ROC) analysis to obtain the prognostic metabolic indices cut-off which may differentiate between benign and malignant lesions. The SUVmax value cut-off at 60 and 90 min p.i. differentiating between normal and abnormal metabolic activity in the pharynx was 1.9 and 2.0, respectively. When compared benign and malignant lesions, the SUVmax on initial and delayed scans were 3.1 and 3.6, respectively. In this material, the increase of the SUVmax value over time of 1.7% suggested abnormality, while RI-SUVmax of 5.7% indicated malignant etiology. The biphasic [18 F]FDG PET/CT study protocol is useful in better stratification of normal and abnormal glucose metabolism activity in the pharynx.

Glycemia after Betamethasone in Pregnant Women without Diabetes-Impact of Marginal Values in the 75-g OGTT.

Betamethasone (BM) administration in pregnancy has been shown to reduce the incidence and severity of neonatal respiratory distress syndrome. Its known diabetogenic impact, combined with placental insulin resistance, leads to a transient increase in glycemia. However, its effect on glucose homeostasis in pregnancy has not been adequately investigated. We closely monitored and assessed the glycemic profile of 83 pregnant women, with normal glucose metabolism, who were given BM during their hospitalization due to threatened premature labor. A significant change in the glycemic profile in most patients was noted, lasting 1.34 ± 1.05 days. Sixty-six of eighty-three women were eventually treated with insulin to maintain glycemia within acceptable limits. The mean ± SD insulin dosage was 12.25 ± 11.28 units/day. The need for insulin therapy was associated with higher BM doses and the presence of marginal values in the 75-g oral glucose tolerance test (OGTT) at 60 min. Our study demonstrates, following BM administration, the need for increased awareness and individualized monitoring/treatment of pregnant women with normal—yet marginal—values in the 75-g OGTT.

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre)diabetes: The Maastricht Study

AimsReactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown. MethodsSubjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO. ResultsFasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h [fasting: 1.12 (95% CI: 0.97–1.29); post-OGTT: 1.19 (1.01–1.41)], eGFR<60mL/min/1.73 m2 [fasting: 1.58 (95% CI: 1.38–1.82), post-OGTT: 1.57 (1.34–1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01–2.53), post-OGTT: 1.38 (0.77–2.48)]. No associations with prior CVD were found. ConclusionFasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.

Reduced corneal nerve fibre length in prediabetes and type 2 diabetes: The Maastricht Study.

PurposeIn individuals with diabetes, injury to the corneal nerve fibres predisposes to delayed corneal epithelial healing, reduced corneal sensitivity and corneal erosion. We investigated to what extent a reduction in corneal nerve fibre length (CNFL) is present in individuals with prediabetes or type 2 diabetes (DM2) compared with individuals with normal glucose metabolism (NGM).MethodsUsing composite images acquired by corneal confocal microscopy, we assessed total CNFL per mm2 in the subbasal nerve plexus of the cornea in 134 participants (mean age 59 ± 8 years, 49% men, 87 NGM, 20 prediabetes, 27 DM2). Multivariable linear regression was used to assess the association between CNFL and glucose metabolism status, adjusted for age and sex.ResultsIn individuals with type 2 diabetes, the mean CNFL was significantly reduced [β = −1.86 mm/mm2 (95% CI −3.64 to −0.08), p = 0.04], as compared with individuals with normal glucose metabolism after adjustment for age and sex. Part of the reduction was present in individuals with prediabetes [β = −0.96 mm/mm2 (95% CI −2.91 to 0.99), p = 0.34], with a linear trend of corneal nerve fibre reduction with severity of glucose metabolism status (p trend = 0.04).ConclusionsA significant reduction in CNFL was found in individuals with DM2 compared with individuals with NGM. A trend of reduction in CNFL was observed between individuals with NGM and prediabetes. The reduction in corneal nerve fibre length could contribute to a delayed corneal healing and an increased risk for corneal complications after surgery.

Lifestyle intervention in the primary prevention of cardiovascular diseases

Cardiovascular diseases are the leading cause of death worldwide. Adherence to ahealthy lifestyle lifelong is capable of significantly reducing the cardiovascular risk by up to 70% and is therefore akey component in primary prevention of cardiovascular disease. According to the European and American guidelines lifestyle interventions include not smoking, daily physical activity of ≥150 min/week at moderate intensity or 75 min/week for higher intensity physical activity, acardioprotective nutrition (high proportion of unsaturated fatty acids, low amounts of saturated fatty acids and low salt intake), normal body weight (body mass index 20-25 kg/m2), arterial blood pressure <140/90 mm Hg (optimum <130/80 mm Hg), low-density lipoprotein (LDL)-cholesterol target values depending on the cardiovascular risk and a normal glucose metabolism in type2 diabetes mellitus with adjustment of aHbA1c to <7%. Lifestyle measures with weight reduction and intensification of physical activity can improve the cardiometabolic risk factors. In this way reduction of the systolic and diastolic blood pressures by approximately 10-15 mm Hg, reduction of HbA1c by approximately 1 % and reduction of triglycerides by ca. 30-40 % are possible. The LDL-cholesterol and lipoprotein(a) levels cannot be easily influenced. Beyond the recommendations for a cardioprotective lifestyle, additional pharmacological therapy may have to be added depending on the cardiovascular risk profile.

Protective Role of CTRP3 and CTRP9 in the Development of Gestational Diabetes Mellitus.

The current study aims to detect the expression of C1q tumor necrosis factor related protein 3 (CTRP3) and CTRP9 in serum of patients with gestational diabetes mellitus (GDM), so as to provide basis for the prevention and treatment of GDM. A total of 129 pregnant women with GDM were selected, and 130 pregnant women with normal glucose metabolism were selected as the control group. The serum levels of CTRP3 and CTRP9 were detected by enzyme-linked immunosorbent assay (ELISA). Pearson's correlation assay was used to compare the correlation between the level of serum CTRP3 and CTRP9 and clinical indicators. ROC analysis was performed to evaluate the diagnostic value of serum CTRP3 and CTRP9. Our data showed that the levels of CTRP3 and CTRP9 in the GDM group were lower than those in the control group, while body mass index (BMI), hemoglobin A1C (HbA1c), hypersensitive C-reactive protein (hs-CRP), IL-6, TNF-α, fasting plasma glucose (FPG), fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) were higher than those in the control group. Pearson's correlation assay showed that serum CTRP3 and CTRP9 was negatively correlated with FPG, FINS, and HOMA-IR. The AUC of the combined diagnosis of GDM was better than that of the single index (0.936 (0.868 - 0.996)), including CTRP3, CTPR9 and FPG. Altogether, low expression of serum CTRP3 and CTRP9 in patients with GDM was negatively correlated with IR and may shed light on revealing the pathogenesis of GDM.

Positive airway pressure normalizes glucose metabolism in obstructive sleep apnea independent of diabetes and obesity

The relationship among obstructive sleep apnea syndrome (OSAS), type 2 diabetes mellitus (DM2) and obesity is very complex and multi-directional. Obesity and increased visceral fat are important perpetuating factors for DM2 in patients with OSAS. On the other hand, OSAS itself leads to obesity by causing both leptin and insulin resistance as a consequence of activation of the sympathetic nervous system. Risk for developing DM2 further increases in patients with OSAS and obesity. Data regarding effects of positive airway pressure (PAP) therapy, gold standard treatment for OSAS, on glycemic control were inconsistent due to variability in duration of and adherence to PAP therapy. In our cohort study we investigated effects of PAP treatment on glucose metabolism in normal-weighted non-diabetic OSAS patients, in obese non-diabetic OSAS patients, and in OSAS patients with DM2. We prospectively analyzed 67 patients diagnosed with OSAS and documented to be effectively treated with PAP therapy for three months. Apnea-hypopnea index was highest in the diabetic group, being significantly higher than in the normal-weighted group (p=0.021). Mean HOMA values were significantly higher in obese (p=0.002) and diabetic group (p=0.001) than normal-weighted group; the differences were still significant after PAP therapy. HbA1c levels were significantly higher in diabetic group compared to those in normal-weighted (p=0.012) and obese (p=0.001) groups. After PAP treatment, decrease in HbA1c levels were significant in normal-weighted (p=0.008), obese (p=0.034), and diabetic (p=0.011) groups. There was no correlation with the change in HbA1c levels and age (p=0.212), BMI (p=0.322), AHI (p=0.098) or oxygen levels (p=0.122). Our study showed that treatment of OSAS by PAP therapy offers beneficial effect on glucose metabolism, not only in diabetic patients, but also in obese and normal-weighted OSAS patients. Although data regarding overall effects of PAP therapy on glycemic control present contradictory results in the literature, it should be emphasized that duration and adherence to PAP therapy were main determinants for beneficial outcome of treatment.

Angiotensin II and transforming growth factor β affect cardiovascular and renal disease in patients with type 2 diabetes mellitus: benefits of dpp-4 inhibitors treatment

BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with impaired glucose metabolism and peripheral insulin resistance, which is accompanied by an high risk of cardiovascular disease (CVD) and nephropathy. Metabolic syndrome and T2DM are accompanied by renin-angiotensin system (RAS) activation, which is also associated with increased risk of CVD and kidney damage. Obesity lead to a wide range of pathophysiological changes, that stimulate cardiac fibrosis, and various fibrosis processes initiation, including activation of transforming growth factor (TGF-).&#x0D; AIMS: To determine activity of angiotensin II (Ang II) and TGF- in patients with obesity and T2DM and their association with heart and kidney damage.&#x0D; MATERIALS AND METHODS: Ang II and TGF- were identified in the peripheral blood of 66 obese patients aged 48-65 years. The first group included 21 patients with coronary heart disease (CHD) and T2DM; The second group included 22 patients with T2DM and excluded CHD; The third group 20 patients with normal glucose metabolism and excluded CHD.&#x0D; RESULTS: The values of TGF- in the 1st group (patients with CHD) were statistically lower than in the group of metabolically healthy obesity (p=0.021). Patients who received DPP-4 inhibitors had a lower Ang II level compared to patients with other hypoglycemic therapy (p=0.005). TGF- positively correlated with glomerular filtration rate (eGFR) in all patients (r=-0.414, p=0.006). TGF- negatively correlated with the degree of internal carotid artery stenosis in patients of the 2nd group (r=-0.42, p=0.09) and LDL-cholesterol in all patients (r=-0.426, p=0.038).&#x0D; CONCLUSIONS: TGF- negatively correlated with the factors that contribute to CVD progression. TGF- correlated with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CHD. DPP-4 inhibitors can improve the cardiovascular prognosis in this group of patients by affecting Ang II level. Low levels of TGF- were associated with higher cardiovascular risk and were commonly found in patients with more severe nephropathy.

Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.

To determine whether HbA1c mismatches (HbA1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1c levels. In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1c was determined from the linear regression modelling the relationship between observed HbA1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles. Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001). Measuring only HbA1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1c in diagnostic classification should be performed in most individuals.

Integrated Proteomics and Metabolomics Analysis Provides Insights into Ganoderic Acid Biosynthesis in Response to Methyl Jasmonate in Ganoderma Lucidum.

Ganoderma lucidum is widely recognized as a medicinal basidiomycete. It was previously reported that the plant hormone methyl jasmonate (MeJA) could induce the biosynthesis of ganoderic acids (GAs), which are the main active ingredients of G. lucidum. However, the regulatory mechanism is still unclear. In this study, integrated proteomics and metabolomics were employed on G. lucidum to globally identify differences in proteins and metabolites under MeJA treatment for 15 min (M15) and 24 h (M24). Our study successfully identified 209 differential abundance proteins (DAPs) in M15 and 202 DAPs in M24. We also identified 154 metabolites by GC–MS and 70 metabolites by LC–MS in M24 that are involved in several metabolic pathways. With an in-depth analysis, we found some DAPs and metabolites that are involved in the oxidoreduction process, secondary metabolism, energy metabolism, transcriptional and translational regulation, and protein synthesis. In particular, our results reveal that MeJA treatment leads to metabolic rearrangement that inhibited the normal glucose metabolism, energy supply, and protein synthesis of cells but promoted secondary metabolites, including GAs. In conclusion, our proteomics and metabolomics data further confirm the promoting effect of MeJA on the biosynthesis of GAs in G. lucidum and will provide a valuable resource for further investigation of the molecular mechanisms of MeJA signal response and GA biosynthesis in G. lucidum and other related species.

Prediabetes Is Associated With Increased Liver Stiffness Identified by Noninvasive Liver Fibrosis Assessment: ElastPQ Ultrasound Shear Wave Elastography Study.

Patients with type 2 diabetes mellitus (DM) have been shown to have increased liver fibrosis (LF) as determined by liver elastography. However, the data on LF incidence in patients with prediabetes are scarce. This study was undertaken to determine the incidence of LF and associated parameters in prediabetic patients. Three study groups with equal number of participants defined on the basis of glucose metabolism status were included the following: normal glucose metabolism (NGM), prediabetes, and newly diagnosed type 2 DM (55 patients in each group). Liver stiffness measurements were carried out using liver elastography point quantification, and 7 kPa or greater was considered to denote the presence of LF. Patients were subdivided into 2 groups as those with or without LF. Of the NGM, prediabetes, and type 2 DM subjects involved in the study 3.6%, 27%, and 38% were found to have LF (P < 0.001), respectively. Glycated hemoglobin (HbA1c), triglycerides, and alkaline phosphatase levels independently correlated with liver stiffness measurements (P < 0.05, for each). In addition, presence of mild or moderate-severe liver steatosis, hypertension, waist circumference, and HbA1c were independent predictors of the LF status. Presence of mild or moderate-severe liver steatosis, hypertension, waist circumference (each 1-cm increment), and HbA1c (each 1% increment) were associated with a 2.78-fold, 7.16-fold, 68%, and 36.7% increased likelihood of LF, respectively. As compared with subjects with NGM, patients with impaired glucose metabolism were more likely to have LF. As in patients with type 2 DM, a significant proportion of patients with prediabetes (27%) have LF, which is closely or independently associated with markers of metabolic syndrome.

The adiponectin receptor agonist AdipoRon normalizes glucose metabolism and prevents obesity but not growth retardation induced by glucocorticoids in young mice

ObjectiveGlucocorticoids (GCs) are highly effective anti-inflammatory and immunosuppressive drugs. However, prolonged GC therapy may cause numerous adverse effects leading to diabetes and obesity, as well as bone disorders such as osteoporosis in adults and growth retardation in children and adolescents. Prevention and care of the GC-induced adverse effects remain challenging. We have previously demonstrated the efficacy of a treatment with a non-peptidic agonist of adiponectin receptors, AdipoRon, to reverse behaviour disorders and fat mass gain induced by long-term GC treatment. In this work, we have established a relevant model of GC-induced growth and metabolic disorders and determined that AdipoRon is a potential therapeutic tool to reverse these metabolic disturbances. Methods5-Week-old mice were treated continuously with or without corticosterone (35 mg/L) in drinking water for seven consecutive weeks. Taking advantage of this mouse model displaying various growth and metabolic disorders, we assayed whether AdipoRon (daily intraperitoneal injection of 1 mg/kg/day for the last 20 days) might prevent the GC-induced adverse effects. The control group was treated with vehicle only. Nutritional behaviors and metabolic parameters were followed-up throughout the treatment. Serum insulin and leptin levels were measured by ELISA. Computed tomography and histological analysis of adipose tissue were assessed at the end of the experimental procedure. ResultsWe found that GC treatment in young mice resulted in continuously increased body weight gain associated with a food intake increase. Compared to vehicle-, GC-treated mice displayed early major hyperleptinemia (up to 6-fold more) and hyperinsulinemia (up to 20-fold more) maintained throughout the treatment. At the end of the experimental procedure, GC-treated mice displayed bone growth retardation (e.g. femur length 15.1 versus 14.0 mm, P < 0.01), higher abdominal adipose tissue volume (4.1 versus 2.3, P < 0.01) and altered glucose metabolism compared to control mice. Interestingly, AdipoRon prevented GC-induced effects on energy metabolism such as abdominal adiposity, insulinemia and leptinemia. However, AdipoRon failed to counteract bone growth retardation. ConclusionWe characterized the very early pathological steps induced by long-term GC in young mice in a relevant model, including growth retardation, fat mass gain and glucose homeostasis dysregulation. The adiponectin system stimulation enabled normalization of the adipose tissue and metabolic features of GC-treated mice. Adiponectin receptor agonists such as AdipoRon might constitute a novel way to counteract some GC-induced adverse effects.

Type II diabetes mellitus and obesity: Common links, existing therapeutics and future developments

Type II diabetes mellitus (T2DM) and obesity are two common pathophysiological conditions of metabolic syndrome (MetS), a collection of similar metabolic dysfunctions due to sedentary lifestyle and overnutrition. Obesity arises from improper adipogenesis which otherwise has a crucial role in maintaining proper metabolic functions. Downstream events arising from obesity have been linked to T2DM. The nuclear receptor peroxisome proliferator activator gamma (PPAR-γ), responsible for maintaining lipid and glucose homeostasis, is down-regulated under obesity leading to a weakened insulin sensitivity of the human body. In course of our review we will outline details of the down-regulation mechanism, provide an overview of the current clinical therapeutics and their shortcomings. Toxicity studies on the seminal drug troglitazone, belonging to the most effective glitazone anti-diabetic category, is also discussed. This will lead to an overview about structural adaptations on the existing glitazones to alleviate their side effects and toxicity. Finally, we forward a concept of novel therapeutics mimicking the glitazone framework, based on some design concepts and preliminary in silico studies. These could be later developed into dual acting drugs towards alleviating the deleterious effects of obesity on normal glucose metabolism, and address obesity in itself.

How Heterogeneity in Glucokinase and Gap-Junction Coupling Determines the Islet [Ca2+] Response

Understanding how cell subpopulations in a tissue impact overall system function is challenging. There is extensive heterogeneity among insulin-secreting β-cells within islets of Langerhans, including their insulin secretory response and gene expression profile, and this heterogeneity can be altered in diabetes. Several studies have identified variations in nutrient sensing between β-cells, including glucokinase (GK) levels, mitochondrial function, or expression of genes important for glucose metabolism. Subpopulations of β-cells with defined electrical properties can disproportionately influence islet-wide free-calcium activity ([Ca2+]) and insulin secretion via gap-junction electrical coupling. However, it is poorly understood how subpopulations of β-cells with altered glucose metabolism may impact islet function. To address this, we utilized a multicellular computational model of the islet in which a population of cells deficient in GK activity and glucose metabolism was imposed on the islet or in which β-cells were heterogeneous in glucose metabolism and GK kinetics were altered. This included simulating GK gene (GCK) mutations that cause monogenic diabetes. We combined these approaches with experimental models in which gck was genetically deleted in a population of cells or GK was pharmacologically inhibited. In each case, we modulated gap-junction electrical coupling. Both the simulated islet and the experimental system required 30–50% of the cells to have near-normal glucose metabolism, fewer than cells with normal KATP conductance. Below this number, the islet lacked any glucose-stimulated [Ca2+] elevations. In the absence of electrical coupling, the change in [Ca2+] was more gradual. As such, electrical coupling allows a large minority of cells with normal glucose metabolism to promote glucose-stimulated [Ca2+]. If insufficient numbers of cells are present, which we predict can be caused by a subset of GCK mutations that cause monogenic diabetes, electrical coupling exacerbates [Ca2+] suppression. This demonstrates precisely how metabolically heterogeneous β-cell populations interact to impact islet function.

Carotid intima-media thickness values are significantly higher in patients with prediabetes compared to normal glucose metabolism.

Carotid intima-media thickness (C-IMT) increases in patients with adult type-2 diabetes mellitus (DM) and is used for early detection of macrovascular complications. We aimed to investigate the change of C-IMT in prediabetes and type-2 DM patients compared to subjects with normal glucose metabolism (NGM).A total of 180 individuals (60 subjects with NGM, 60 patients with prediabetes and 60 patients with type-2 DM) were included in this study. Routine laboratory and micro-macrovascular involvement were investigated. Urine albumin-creatinine ratio (ACR) was measured for urinary albuminuria detection. In addition to routine laboratory examination, right-left common and internal C-IMT (CC-IMT and IC-IMT) were measured.Systolic and diastolic blood pressure values were found to be higher in prediabetes and type-2 DM groups than NGM group. The prevalence of nephropathy and presence of CAD were higher in type-2 DM groups than prediabetes. Glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood urea nitrogen, creatinine, high sensitive C reactive protein (hs-CRP) levels and urinary ACR were significantly higher in patients within prediabetes and type-2 DM groups than NGM group. Glucose, HbA1c and hs-CRP levels were found to be higher in type-2 DM groups than prediabetes. Estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol level was found to be lower in patients within prediabetes and type-2 DM groups than NGM group. Right-left-mean CC-IMT and IC-IMT values were found to be higher in prediabetes and type-2 DM groups than NGM group. Left IC-IMT, left CC-IMT, and mean IC-IMT values were found to be higher in type-2 DM patients compared to prediabetes. LDL and HDL cholesterols, HbA1c, and hs-CRP levels were independently associated with IC-IMT and CC-IMT.C-IMT values were significantly higher in impaired glucose metabolism compared to NGM. C-IMT measurement may be used as part of routine screening of macrovascular complication in patients with prediabetes and newly diagnosed type-2 DM.

Adverse differences in cardiometabolic risk factor levels between individuals with pre-diabetes and normal glucose metabolism are more pronounced in women than in men: the Maastricht Study

ObjectiveTo investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2...

Glucose metabolism affects coagulation factors: The NEO study

BackgroundIt is insufficiently understood if there is an association between diabetes and VT, and what the underlying mechanism would be. ObjectivesWe aimed to study the association between glucose concentrations with several coagulation factors in the general population. MethodsThis is a cross‐sectional analysis of baseline measurements within 5778 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population‐based cohort study of individuals 45 to 65 years. Associations between fasting glucose and HbA1c concentrations, and postprandial glucose response and factor (F) VIII, FIX, FXI, and fibrinogen levels were examined using linear regression analyses and by calculating mean levels per category of glucose concentrations while adjusting for confounding factors. ResultsPer each mmol/L higher fasting glucose concentration we observed higher levels of fasting FVIII (5.33%, 95% CI: 4.00‐6.65), FIX (6.19%, 95% CI: 5.15‐7.23), and FXI (2.11%, 95% CI: 1.20‐3.02). Results for fasting HbA1c and postprandial glucose response were similar. Participants with an impaired fasting glucose, high fasting glucose, and diabetes mellitus had higher mean levels of FVIII, FIX, and FXI than those with a normal glucose metabolism, with the highest differences in the levels of FVIII, FIX, and FXI between a high fasting glucose and a normal glucose metabolism. All associations attenuated after adjustment for total body fat, yet all of the above associations remained after adjustment for the confounding factors, except for fibrinogen when contrasted to glucose. ConclusionConcentrations of fasting glucose and HbA1c and postprandial glucose response were positively associated with FVIII, FIX, and FXI, and to some extent also with fibrinogen.

High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of cardiovascular outcome: The CODAM study

Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited. In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM). Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n=150 cases) and history of CV events (CVE, n=85 cases) in an observational cohort (CODAM, n=574, 59.6±0.3yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism. HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P<.05) and CVE (ORs 0.61 to 0.68, P<.05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction=.074 and .034, respectively), but not in those with NGM. HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.

White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes: The Maastricht Study.

Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed. In the Maastricht Study, a type 2 diabetes-enriched population-based cohort study (1,361 subjects with normal glucose metabolism, 348 with prediabetes, and 510 with type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors. Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = -0.055 [95% CI -0.172, 0.062], stβType2diabetes = -0.256 [-0.379, -0.133], P trend < 0.001). Prediabetes was associated with lower local efficiency (stβ = -0.084 [95% CI -0.159, -0.008], P = 0.033) and lower clustering coefficient (stβ = -0.097 [95% CI -0.189, -0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008). These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections.