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Aims: Dysglycemia, including the three domains hyperglycemia, hypoglycemia, and increased glycemic variability (GV), is associated with high mortality among critically ill patients. However, this association differs by diabetes status, and reports in this regard are limited. This study aimed to evaluate the associations between the three dysglycemia domains and mortality in critically ill patients by diabetes status and determined the contributing factors for dysglycemia. Methods: This retrospective study included 958 critically ill patients (admitted to the ICU) with or without DM. Dysglycemia was defined as abnormality of any of the three dimensions. We evaluated the effects of the three domains of glucose control on mortality using binary logistic regression and then adjusted for confounders. The associations between dysglycemia and other variables were investigated using cumulative logistic regression analysis. Result: GV independently and similarly affected mortality in both groups after adjustment for confounders (DM: odds ratio [OR], 1.05; 95% confidence interval [CI]: 1.03-1.08; p <0.001; non-DM: OR, 1.07; 95% CI, 1.03-1.11; p = 0.002). Hypoglycemia was strongly associated with ICU mortality among patients without DM (3.12; 1.76-5.53; p <0.001) and less so among those with DM (1.18; 0.49-2.83; p = 0.72). Hyperglycemia was non-significantly associated with mortality in both groups. However, the effects of dysglycemia seemed cumulative. The factors contributing to dysglycemia included disease severity, insulin treatment, glucocorticoid use, serum albumin level, total parenteral nutrition, duration of diabetes, elevated procalcitonin level, and need for mechanical ventilation and renal replacement therapy. Conclusion: The association between the three dimensions of dysglycemia and mortality varied by diabetes status. Dysglycemia in critical patients is associated with excess mortality; however, glucose management in patients should be specific to the patient's need considering the diabetes status and broader dimensions. The identified factors for dysglycemia could be used for risk assessment in glucose management requirement in critically ill patients, which may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Identifying the earliest moment for intervention to avert progression to prediabetes and diabetes in high-risk individuals is a substantial challenge. As β-cell function is already compromised in prediabetes, attention should therefore be focused on identifying high-risk individuals earlier in the so-called pre-prediabetes stage. Biomarkers to monitor progression and identify the time point at which β-cell dysfunction occurs are therefore critically needed. Large-scale population studies have consistently shown that the 1-h plasma glucose (1-h PG) ≥ 155 mg/dl (8.6 mmol/l) during the oral glucose tolerance test detected incident type 2 diabetes and associated complications earlier than fasting plasma glucose or 2-h plasma glucose levels. An elevated 1-h PG level appears to be a better alternative to HbA1c [5.7-6.4% (37-47 mmol/mol)] or traditional glucose criteria for identifying high-risk individuals at a stage when ß-cell function is substantially more intact than in prediabetes. Diagnosing high-risk individuals earlier proffers the opportunity for potentially reducing progression to diabetes, development of microvascular complications and mortality, thereby advancing benefit beyond that which has been demonstrated in global diabetes prevention programs. [ABSTRACT FROM AUTHOR]

Aim: To assess the performance of HbA1c and the 1-h plasma glucose (PG ≥ 155 mg/dl; 8.6 mmol/l) in identifying dysglycemia based on the oral glucose tolerance test (OGTT) from a real-world clinical care setting. Methods: This was a diagnostic test accuracy study. For this analysis, we tested the HbA1c diagnostic criteria advocated by the American Diabetes Association (ADA 5.7-6.4 %) and International Expert Committee (IEC 6.0-6.4 %) against conventional OGTT criteria. We also tested the utility of 1-h PG ≥ mg/dl; 8.6 mmol/l. Prediabetes was defined according to ADA-OGTT guidelines. Spearman correlation tests were used to determine the relationships between HbA1c, 1-h PG with fasting, 2-h PG and indices of insulin sensitivity and β-cell function. The levels of agreement between diagnostic methods were ascertained using Cohen's kappa coefficient ( Κ). Receiver operating characteristic (ROC) curve was used to analyze the performance of the HbA1c and 1-h PG test in identifying prediabetes considering OGTT as reference diagnostic criteria. The diagnostic properties of different HbA1c thresholds were contrasted by determining sensitivity, specificity and likelihood ratios (LR). Results: Of the 212 high-risk individuals, 70 (33 %) were identified with prediabetes, and 1-h PG showed a stronger association with 2-h PG, insulin sensitivity index, and β-cell function than HbA1c ( P < 0.05). Furthermore, the level of agreement between 1-h PG ≥ 155 mg/dl (8.6 mmol/l) and the OGTT ( Κ[95 % CI]: 0.40[0.28-0.53]) diagnostic test was stronger than that of ADA-HbA1c criteria 0.1[0.03-0.16] and IEC criteria (0.17[0.04-0.30]). The ROC (AUC[95 % CI]) for HbA1c and 1-h PG were 0.65[0.57-0.73] and 0.79[0.72-0.85], respectively. Importantly, 1-h PG ≥ 155 mg/dl (8.6 mmol/l) showed good sensitivity (74.3 % [62.4-84.0]) and specificity 69.7 % [61.5-77.1]) with a LR of 2.45. The ability of 1-h PG to discriminate prediabetes was better than that of HbA1c (∆AUC: −0.14; Z value: 2.5683; P = 0.01022). Conclusion: In a real-world clinical practice setting, the 1-h PG ≥ 155 mg/dl (8.6 mmol/l) is superior for detecting high-risk individuals compared with HbA1c. Furthermore, HbA1c is a less precise correlate of insulin sensitivity and β-cell function than the 1-h PG and correlates poorly with the 2-h PG during the OGTT. [ABSTRACT FROM AUTHOR]

Aims: Non-diabetic children with multiple islet autoantibodies were recruited to a secondary prevention trial. The objective was to determine the predictive value of baseline (1) HbA1c and metabolic variables derived from intravenous (IvGTT) and oral glucose tolerance tests (OGTT), (2) insulin resistance and (3) number, type and levels of islet autoantibodies, for progression to type 1 diabetes. Methods: Children [ n = 50, median 5.1 (4-17.9) years] with autoantibodies to glutamate decarboxylase (GAD65A) and at least one of insulinoma-associated protein 2 (IA-2A), insulin or ZnT8 transporter (ZnT8RA, ZnT8WA, ZnT8QA) were screened with IvGTT and OGTT and followed for a minimum of 2 years. Results: Baseline first phase insulin response (sum of serum-insulin at 1 and 3 min during IvGTT; FPIR) ≤3 μU/mL [HR 4.42 (CI 1.40-14.0) p = 0.011] and maximal plasma glucose ≥11.1 mmol/L measured at 30, 60 and/or 90 min during OGTT [HR 6.13 (CI 1.79-21.0) p = 0.0039] were predictors for progression to diabetes. The combination of FPIR from IvGTT and maximal plasma glucose during OGTT predicted diabetes in 10/12 children [HR 9.17 (CI 2.0-42.0) p = 0.0043]. High-level IA-2A, but not number of autoantibodies, correlated to dysglycemia during OGTT ( p = 0.008) and to progression to type 1 diabetes [HR 4.98 (CI 1.09-22.0) p = 0.039]. Conclusions: Baseline FPIR, maximal plasma glucose ≥11.1 at 30, 60 or 90 min during OGTT and high-level IA-2A need to be taken into account when randomizing islet autoantibody positive non-diabetic children to secondary prevention. [ABSTRACT FROM AUTHOR]