Dysglycemic States Research Articles

Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Therefore, interrupting the vicious cycle within neuron-microglia interactions by promoting neuroprotective effects or inhibiting the neurotoxic effects of the CX3CL1-CX3CR1 signaling axis may be a therapeutic goal in DE by limiting the inflammatory response. However, the optimal approach to prevent DE is simply tight glycemic control, because the elimination of dysglycemic states in the CNS abolishes the fundamental mechanisms that induce this vicious cycle.

Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures

Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.

Dysglycemia and arrhythmias.

Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.

Serum Levels of Activin A: Predictor of Insulin Resistance and Atherosclerosis in Prediabetics.

Pathological effects of dysglycemia and insulin resistance on atherosclerosis and cardiac remodeling starts as early as in the prediabetic state before the onset of overt diabetes. Activin A is a molecule with multiple functions, including an important part in glucose homeostatic mechanisms as well as inflammatory processes and is therefore being researched as a useful novel biomarker for prompt recognition of the risk of cardiovascular disease (CVD) in prediabetic individuals, thereby helping in disease prognostication and early institution of therapeutic measuresObjective: The study aimed to measure serum levels of activin A in prediabetic patients and evaluate them in comparison to normoglycemic controls. The association of activin A with carotid intima media thickness (CIMT), left ventricular diastolic dysfunction (LVDD), and homeostatic assessment of insulin resistance (HOMA-IR) was also studiedMaterials and methods: A total of 60 prediabetic cases and 60 normoglycemic control subjects [matched as per age, gender, and body mass index (BMI)] were recruited. Measurement of serum glucose levels (fasting and postprandial) and fasting insulin levels and glycated hemoglobin (HbA1c) levels were done in all the subjects. The values of HOMA-IR were computed using established formulae. Enzyme-linked immunosorbent assay (ELISA) kits were used for the evaluation of serum levels of activin A in both groups. Parameters for the two groups were compared. In the cases, CIMT (using B-mode ultrasound) and LVDD (using two-dimensional (2D) echocardiography) were measured and correlated with activin A levelsResults: Serum fasting insulin (mIU/L) was considerably higher in cases than in the controls (p < 0.001). HOMA-IR median [interquartile range (IQR)] was 4 (3.25-4.93) in some cases, and that in the control group was 1.2 (0.88-1.5) (p < 0.001). Serum activin A levels in the cases group had a median (IQR) of 263.55 (227.1-279.5) ng/mL, which was substantially greater as compared to the control group 159.9 (150.7-178.7) ng/mL (p < 0.001). A significant positive association of serum activin A levels with HOMA-IR (ρ = 0.75, p < 0.001) and CIMT (ρ = 0.50, p < 0.001) was found. In LVDD grade I and II groups, the serum levels of activin A were 257.86 (219.3-271.2) ng/mL and 269 (244.19-291.5) ng/mL, respectively (p = 0.12)Conclusion: A substantial proportion of morbidity and mortality related to dysglycemic states can be attributed to cardiovascular complications. Elevated levels of activin A in prediabetes can act as an indicator of subclinical CVD leading to early diagnosis and intervention.

CGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study.

Continuous glucose monitoring (CGM) parameters may identify individuals at risk for progression to overt type 1 diabetes. We aimed to determine whether CGM metrics provide additional insights into progression to clinical stage 3 type 1 diabetes. One hundred five relatives of individuals in type 1 diabetes probands (median age 16.8 years; 89% non-Hispanic White; 43.8% female) from the TrialNet Pathway to Prevention study underwent 7-day CGM assessments and oral glucose tolerance tests (OGTTs) at 6-month intervals. The baseline data are reported here. Three groups were evaluated: individuals with 1) stage 2 type 1 diabetes (n = 42) with two or more diabetes-related autoantibodies and abnormal OGTT; 2) stage 1 type 1 diabetes (n = 53) with two or more diabetes-related autoantibodies and normal OGTT; and 3) negative test for all diabetes-related autoantibodies and normal OGTT (n = 10). Multiple CGM metrics were associated with progression to stage 3 type 1 diabetes. Specifically, spending ≥5% time with glucose levels ≥140 mg/dL (P = 0.01), ≥8% time with glucose levels ≥140 mg/dL (P = 0.02), ≥5% time with glucose levels ≥160 mg/dL (P = 0.0001), and ≥8% time with glucose levels ≥160 mg/dL (P = 0.02) were all associated with progression to stage 3 disease. Stage 2 participants and those who progressed to stage 3 also exhibited higher mean daytime glucose values; spent more time with glucose values over 120, 140, and 160 mg/dL; and had greater variability. CGM could aid in the identification of individuals, including those with a normal OGTT, who are likely to rapidly progress to stage 3 type 1 diabetes.

NDSP-10: The Cardiometabolic Risk Profile with Various Degrees of Dysglycemia in Younger and Older Adults: Findings from the Second National Diabetes Survey of Pakistan 2016-2017.

Background: To assess and compare the cardiometabolic risk profile of the Pakistani population between younger (<45 years) and older adults (≥45 years). Methods: This is a substudy of a nationally representative community-based epidemiological second National Diabetes Survey of Pakistan (NDSP) 2016-2017. Out of 12,486 individuals approached, 10,834 participants agreed to be included (response rate 87%). Cardiovascular risk factors assessed were obesity, central obesity, hypertension, diabetes, hyperlipidemia, and tobacco use. Participants were stratified into young adults (<45 years) and older adults (≥45 years) and was subcategorized into four groups that is, diagnosed diabetes mellitus (DM), undiagnosed DM, prediabetes, and without diabetes. Results: Around 14.3% were prediabetes, 8.8% were undiagnosed DM, and 24% were diagnosed diabetes. Most participants in dysglycemic (prediabetes, undiagnosed DM, and diagnosed DM) groups were females and were from rural regions. Cardiovascular disease (CVD) risk factors were more noted in dysglycemic states, compared with without diabetes. Overall CVD risk profile was worse in males in both age categories, although the accumulation of four or five CVD risk factors at one point was more predominant in females in either age group. Conclusion: Overall, the preponderance of CVD risk factors, such as overweight, obesity, central obesity, tobacco use, ex-tobacco uses, and dyslipidemia, were substantially more prevalent in dysglycemia groups of young adults (<45 years) compared with older adults (≥45 years). Early and targeted intervention in young may prevent poor CVD outcomes as they age.

Clinical Laboratorial Perspective on Screening of Prediabetes and need for Standardization of Post Prandial Blood Glucose Testing in Nepal

This study explores the differences in categorization of prediabetes based on fasting blood glucose by the World Health Organization and the American Diabetes Association from a laboratory perspective and the associated implications. As the diagnostic thresholds for prediabetes are based on the likelihood of developing overt diabetes, the criteria for this collective representation of dysglycemic states, including Impaired Fasting Glucose and Impaired Glucose Tolerance needs to be clearly established in the face of a society that grows increasingly concerned about diabetes and its associated complications over time. The authors intend to delve into different published points of view and recommend a categorization in Nepal’s context.

Use of hemoglobin A1c to identify dysglycemia in cystic fibrosis.

BackgroundCystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%–50% of people with CF eventually develop CF–related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states.ObjectiveTo determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs.MethodsThis retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states.ResultsMean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250).ConclusionThere is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

Abstract P616: Characterization of the Associations Between Pre-Diabetes and Diabetes With Occurrence of Stroke by Its Types, Subtypes and Outcomes Among West Africans

Background: Pre-diabetes and diabetes mellitus (DM) are dysglycemic states associated with stroke occurrence. However, there is limited data from sub-Saharan Africa on the burden and associations between pre-DM and DM and stroke occurrence in a region experiencing an astronomic rise in stroke burden Purpose: To characterize the associations between stroke occurrence, types, subtypes, severity and outcome indicators according to glycemic status among West Africans. Methods: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular, lifestyle, psychosocial factors, stroke severity and outcomes were performed. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. Results: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. The frequencies of euglycemia, pre-DM and DM among age- and sex-matched stroke-free controls were 69.2%, 13.3% and 17.5% respectively. Pre-diabetes was independently associated with stroke, adjusted odds ratio (95% CI) of 3.68 (2.61 - 5.21) as was having DM, aOR of 4.29 (3.19 - 5.74). The effect size of Pre-DM for ischemic stroke of 3.06 (95% CI: 2.01 - 4.64) was lower than that for DM of 4.82 (3.37-6.89). However, the effect size of Pre-DM for hemorrhagic stroke of 6.81 (95% CI: 3.29 - 14.08) is higher than 3.36 (1.94 - 5.86) for DM. Furthermore, the effect sizes of pre-DM for ischemic stroke subtypes were 9.64 (95% CI: 1.30-71.57) for cardio-embolic stroke, 3.64 (95% CI: 1.80-7.34) for small-vessel occlusive disease and 4.63 (95% CI: 0.80-26.65) for large-vessel disease. Conclusion: Every 2 out of 3 stroke cases admitted had a blood glucose abnormality. In addition to confirming the known associations between DM and stroke occurrence, we demonstrate that pre-DM is independently and more potently associated with hemorrhagic than ischemic strokes among West Africans.

The Oral Glucose Tolerance Test: 100 Years Later.

For over 100 years, the oral glucose tolerance test (OGTT) has been the cornerstone for detecting prediabetes and type 2 diabetes (T2DM). In recent decades, controversies have arisen identifying internationally acceptable cut points using fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and/or HbA1c for defining intermediate hyperglycemia (prediabetes). Despite this, there has been a steadfast global consensus of the 2-h PG for defining dysglycemic states during the OGTT. This article reviews the history of the OGTT and recent advances in its application, including the glucose challenge test and mathematical modeling for determining the shape of the glucose curve. Pitfalls of the FPG, 2-h PG during the OGTT, and HbA1c are considered as well. Finally, the associations between the 30-minute and 1-hour plasma glucose (1-h PG) levels derived from the OGTT and incidence of diabetes and its complications will be reviewed. The considerable evidence base supports modifying current screening and diagnostic recommendations with the use of the 1‐h PG. Measurement of the 1‐h PG level could increase the likelihood of identifying high-risk individuals when the pancreatic ß-cell function is substantially more intact with the added practical advantage of potentially replacing the conventional 2‐h OGTT making it more acceptable in the clinical setting.

Mesa 2: Insuficiencia cardíaca y diabetes mellitus tipo 2

Desde que el estudio Framingham en 1974 reportó un aumento de dos a cinco veces en el riesgo de desarrollar insuficiencia cardíaca (IC) en pacientes con diabetes mellitus (DM), otros estudios observacionales confirmaron esta asociación que ha tomado gran visibilidad en los últimos años a partir de los resultados de los estudios de seguridad cardiovascular de las drogas antidiabéticas.La IC se define como un síndrome clínico que resulta del deterioro funcional o estructural del llenado ventricular o la eyección de sangre. Puede clasificarse según la fracción de eyección, la presencia de síntomas y la limitación de la actividad física.Existen distintos factores asociados a la IC en personas con DM como la edad, la antigüedad de la enfermedad, la utilización de insulina, la enfermedad coronaria, la hipertensión arterial, la enfermedad arterial periférica, el aumento de creatinina, el escaso control glucémico, la albuminuria y la obesidad. A su vez la IC se asocia a insulinorresistencia y a estados disglucémicos que se consideran de riesgo para el desarrollo de DM.

Risk Factor Control in Stroke Survivors with Diagnosed and Undiagnosed Diabetes: A Ghanaian Registry Analysis

Background and PurposeExpert consensus guidelines recommend optimizing global risk factor control in diabetic stroke survivors to improve outcomes. Since relatively little is known about the adequacy of risk factor control among diabetic stroke survivors in sub-Saharan Africa, we sought to assess control rates of key traditional risk factors among Ghanaian stroke survivors with diabetes. A secondary objective was to assess the burden of undiagnosed dysglycemic states among stroke survivors without a prior diagnosis of diabetes mellitus (DM) MethodsCross-sectional study of outpatient stroke survivors consecutively enrolled in a stroke registry at a tertiary medical center in Ghana between January 2018 and March 2020. We collected baseline demographic and clinical details including blood pressure, lipid panel, fasting blood glucose results, medications prescribed for secondary prevention, and stroke type information. BP control target was set at <130/80 mmHg, LDL-cholesterol <2.6 mmol/l and Fasting blood glucose (FBG) <7.0 mmol/l. Factors associated with poor control of vascular risk factors were assessed using multivariate logistic regression models. ResultsOf 1101 stroke survivors enrolled into the registry, 279 (25.3%) had a comorbid diagnosis of DM. Mean (±SD) age among the diabetic vs. non-diabetic stroke patients was 61.4 ± 12.0 years vs. 57.6 ± 14.6 years (p < 0.0001). Among the diabetic stroke patients, 61.7% had LDL-cholesterol <2.6 mmol/L, 8.2% had BP <130/80 mm Hg and 28.6% had FBG <7.0 mmol/L. Significant predictors of poor control of BP were younger age, having co-morbid DM and number of antihypertensive medication classes while poor LDL-cholesterol was associated with longer duration of stroke diagnosis. Among those without a prior diagnosis of DM, FBG analysis of 540 subjects with available data showed that 21.7% had FBG <5.7 mmol/L, 39.0% had impaired fasting blood glucose and 39.3% had FBG in the diabetes mellitus range. Patients who were older, female, or experienced an ischemic stroke trended towards being more likely to have undiagnosed DM. ConclusionAmong Ghanaian diabetic stroke survivors, blood pressure and blood glucose, are especially poorly controlled. There is also a high burden of undiagnosed pre-diabetes and DM among stroke survivors substantially heightening their risk for further adverse CVD outcomes.

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

Prediabetic Dysglycemia: Call for Action.

Different dysglycemic states precede overt type 2 diabetes. Prediabetic dysglycemia also carries an increased cardiovascular risk per se. Prediabetic dysglycemia may be divided into impaired fasting glycemia, impaired glucose tolerance and intermediate hyperglycemia. Mixed forms of these are very common. Dysglycemia develops insidiously for many years and usually produces no symptoms until very late. It is possible to prevent prediabetic dysglycemia from progressing to manifest type 2 diabetes and it can also be made to return to normoglycemia. The importance of lifestyle interventions, pharmacological treatment, surgical treatment and community efforts are discussed.

Abstract TP225: Coated-Platelet Levels Are Associated With Chronic Hyperglycemia and Systemic Inflammation in Acute Ischemic Stroke

Introduction: Elevated levels of coated-platelets (a subset of procoagulant platelets) are often associated with acute ischemic stroke (AIS). Diabetes mellitus (DM) and chronic inflammation are both known risks factor for AIS. Elevated neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) are also often seen in the setting of acute myocardial infarction and AIS. However, the relationship between prothrombotic, dysglycemic and proinflammatory states in AIS is incompletely characterized. Hypothesis: To investigate whether elevated coated-platelet levels in AIS patients with chronic hyperglycemia is associated with proinflammatory states. Methods: The present cohort consists of patients with AIS or transient ischemic attack (TIA) due to large-artery disease over the period of one year. Coated-platelet levels were assayed upon admission. Glycated hemoglobin (HbA1c) and leukocyte count with differential were obtained through retrospective chart review. Study population was subcategorized into DM (HbA1c &gt;6.4 and/or history of DM), prediabetic (PD, HbA1c 5.7-6.4) and non-diabetic (ND, HbA1c &lt;5.7). Inter-relationship was assessed using linear regression models. Results: We recruited 47 AIS/TIA patients, with an average age of 67.3±8.1 years and 17/47 (36.2%) being current smokers. Thirty of 47 patients (63.8%) were diabetic with 23 patients having HbA1c levels &gt;6.4. Higher coated-platelet levels were associated with higher lymphocyte count for the entire group (r=+0.375; p=0.0094) and also for the patients with HbA1c &gt;6.4 (r=+0.516; p=0.012; n=23). Although PLR and HbA1c &gt;6.4 showed a positive correlation (r=+0.42; p=0.046; n=23) in DM patients, this was not observed among DM patients with HbA1c &lt;6.4. Conclusion: Our study demonstrates positive correlations between elevated coated-platelets and lymphocyte count and between PLR and HbA1c in AIS/TIA patients with HbA1c &gt;6.4. This alludes to a synergistic role for procoagulant and proinflammatory states in chronically dysglycemic AIS/TIA patients.

898-P: CGM Metrics Identify Dysglycemic States in Subjects with Normal OGTT from the TrialNet Pathway to Prevention Study

The TrialNet Pathway to Prevention Study (PtP) has enhanced our understanding of the progression through the stages of T1D identifying individuals at early stages of disease for prevention trials. Individuals with multiple islet AAb and normal OGTT are considered to be at Stage 1 T1D, and those with abnormal OGTT are at Stage 2 T1D. Our aim was to determine whether subtle forms of dysglycemia provide new clues about disease progression (Stage 3). 94 relatives of T1D probands from PtP underwent a 7-day CGM assessment (Dexcom G4 Platinum Professional) Three groups of relatives were evaluated: 1) Relatives at Stage 2 T1D whose 5-year risk for T1D progression is ∼70% (n=33); 2), relatives at Stage 1 T1D whose 5-year risk for T1D progression is ∼ 35% (n=51); and relatives with negative confirmed AAb and normal OGTT (n=10) whose 5-year risk for progression is &amp;lt;1%. CGM variations occur in a significant number of subjects with Stage 1 T1D (Figure) with increased variation in CGM glucose values assessed by mean amplitude of glucose excursion (MAGE) in relatives (n= 4 Stage 0; 31 Stage 1; and 27 Stage 2) at Stage 1 and Stage 2 T1D compared to that of low risk relatives (P = 0.005). Interstitial glucose &amp;gt;140 mg/dL was higher in relatives at Stage 1 and Stage 2 T1D compared to low risk relatives (P = 0.02). In conclusion, CGM metrics may be useful in identifying dysglycemia in at risk relatives with normal OGTT. Disclosure D.M. Wilson: Advisory Panel; Self; Tolerion, Inc. Research Support; Self; Beta Bionics, Dexcom, Inc., Medtronic. P. Nelson: None. D. Scheinker: Advisory Panel; Self; Carta Healthcare. S. Pietropaolo: None. M. Acevedo-Calado: None. M. Ebrahimi: None. A. Steck: None. J.L. Dunne: None. C. Greenbaum: Research Support; Self; Janssen Research &amp; Development. M. Pietropaolo: None. Funding National Institutes of Health

Dysglycemic states and hypertension: A relationship dependent on low-grade inflammation

Background: Hypertension (HTN) is a prominent cardiovascular risk factor, affecting over 1 billion people worldwide. Identification of closely associated cardiometabolic conditions may be crucial for its early detection. The objective of this study was to identify factors associated with HTN and prehypertension (PHT) in an adult population sample from Maracaibo City, Venezuela. Methods: A randomized multi-staged sampling cross-sectional study was performed in 2230 individuals from Maracaibo City Metabolic Syndrome Prevalence Study database. PHT and HTN were defined according to JNC-7 criteria. Multiple logistic regression analysis was used to assess the main risk factors for each condition. Results: 52.6% (n=1172) of the subjects were female, the prevalence of HTN was 32% (n=714), while the prevalence of PHT was 31.1% (n=693). The main risk factors for HTN were age ≥60 years (odds ratio [OR]: 40.99; 95%CI: 16.94-99.19; p&lt;0.001) and the local indigenous ethnic group (OR: 3.06; 95%CI: 1.09-8.62; p=0.03). Adjustment for high sensitivity C-reactive protein levels increased the OR of these factors and diminished the impact of other factors. Meanwhile, age ≥60 years (OR: 3.39; 95%CI: 1.41-8.18; p=0.007) and alcohol consumption (OR: 1.49; 95%CI: 1.06-2.00; p=0.02) were the main risk factors for PHT. Conclusion: There are significant differences in the risk factor profiles for HTN and PHT. Additionally, low-grade inflammation appears to link multiple metabolic factors and preexisting vascular characteristics.

An elevated 1-h post- load glucose level during the oral glucose tolerance test detects prediabetes

AimThe objective of the study was to compare the diagnosis of dysglycemic states by conventional oral glucose tolerance test (OGTT) criteria (fasting and 2-h plasma glucose) with the 1-h post-load plasma glucose level. Material and methods34 individuals (mean age: 55±13years; BMI: 27.7±6.3kg/m2) at risk for prediabetes were administered a 75g OGTT. Individuals with normal glucose tolerance (NGT) or prediabetes were identified according to fasting and/or 2-h plasma glucose (PG) concentrations. Subsequently, subjects were divided in 2 groups: group 1 (n=21) with a 1-h PG<155mg/dl and group 2 (n=13) with a 1-h PG≥155mg/dl. HOMA was performed to assess β-cell function and insulin sensitivity. ResultsNGT or prediabetes based on conventional criteria correlated with the 1-h PG<or≥155mg/dl (p<0.001). Moreover, the 1-h PG≥155mg/dl was associated with higher HbA1c levels (6.1±0.5 vs. 5.5±0.3%, p<0.001) and significantly impaired insulin secretion and hyperbolic product (BxS) on HOMA test vs. 1-h PG<155mg/dl. ConclusionThe 1-h post-load plasma glucose value ≥155mg/dl is strongly associated with conventional criteria for (pre)diabetes and alterations of β-cell function.

Diabetes and Impaired Fasting Glucose Prediction Using Anthropometric Indices in Adults from Maracaibo City, Venezuela.

To determine the predictive power of various anthropometric indices for the identification of dysglycemic states in Maracaibo, Venezuela. A cross-sectional study with randomized, multi-staged sampling was realized in 2230 adult subjects of both genders who had their body mass index (BMI), waist circumference (WC) and waist-height ratio (WHR) determined. Diagnoses of type 2 diabetes mellitus (DM2) and impaired fasting glucose (IFG) were made following ADA 2015 criteria. ROC curves were used to evaluate the predictive power of each anthropometric parameter. Area under the curve (AUC) values were compared through Delong's test. Of the total 2230 individuals (52.6% females), 8.4% were found to have DM2, and 19.5% had IFG. Anthropometric parameters displayed greater predictive power regarding newly diagnosed diabetics, where WHR was the most important predictor in both females (AUC=0.808; CI 95% 0.715-0.900. Sensitivity: 82.8%; specificity: 76.2%) and males (AUC=0.809; CI 95% 0.736-0.882. Sensitivity: 78.6%; specificity: 68.1%), although all three parameters appeared to have comparable predictive power in this subset. In previously diagnosed diabetic subjects, WHR was superior to both WC and BMI in females, and WHR and WC were both superior to BMI in males. Lower predictive values were found for IFG in both genders. Accumulation of various altered anthropometric measurements was associated with increased odds ratios for both newly and previously diagnosed DM2. The predictive power of anthropometric measurements was greater for DM2 than IFG. We suggest assessment of as many available parameters as possible in the clinical setting.

Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management.

New-onset diabetes after transplantation (NODAT) is major complication following renal transplantation. It commonly develops within 3-6 mo post-transplantation. The development of NODAT is associated with significant increase in risk of major cardiovascular events and cardiovascular death. Other dysglycemic states, such as impaired glucose tolerance are also associated with increasing risk of cardiovascular events. The pathogenesis of these dysglycemic states is complex. Older recipient age is a consistent major risk factor and the impact of calcineurin inhibitors and glucocorticoids has been well described. Glucocorticoids likely cause insulin resistance and calcineurin inhibitors likely cause β-cell toxicity. The impact of transplantation in incretin hormones remains to be clarified. The oral glucose tolerance test remains the best diagnostic test but other tests may be validated as screening tests. Possibly, NODAT can be prevented by administering insulin early in patients identified as high risk for NODAT. Once NODAT has been diagnosed altering immunosuppression may be acceptable, but creates the difficulty of balancing immunological with metabolic risk. With regard to hypoglycemic use, metformin may be the best option. Further research is needed to better understand the pathogenesis, identify high risk patients and to improve management options given the significant increased risk of major cardiovascular events and death.